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Textbook of Endocrine Surgery Second Edition Orlo
Clark Digital Instant Download
Author(s): Orlo Clark, Quan-Yang Duh, Electron Kebebew
ISBN(s): 9780721601397, 0721601391
Edition: 2
File Details: PDF, 37.00 MB
Year: 2005
Language: english
ELSEVIER
SAUNDERS
1600 John F. Kennedy Blvd., Ste 1800
Philadelphia, PA 19103-2899

TEXTBOOK OF ENDOCRINE SURGERY

Copyright© 2005, 1997 Elsevier Inc. ISBN 0-7216-0139-1

All rights reserved. No part of this publication may be reproduced or transmitted in any form or by
any means, electronic or mechanical, including photocopying, recording, or any information storage
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Libraryof CongressCataloging-in-Publication Data

NOTICE

Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our knowledge, changes in practice, treatment and drug therapy may become necessary or
appropriate. Readers are advised to check the most current information provided (i) on procedures
featured or (ii) by the manufacturer of each product to be administered, to verify the recommended
dose or formula, the method and duration of administration, and contraindications. It is the
responsibility of the practitioner, relying on their own experience and knowledge of the patient, to
make diagnoses, to determine dosages and the best treatment for each individual patient, and to
take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the
EditorslAuthors assumes any liability for any injury and/or damage to persons or property arising
out or related to any use of the material contained in this book.

Textbook of endocrine surgery / [edited by] Orlo H. Clark, Quan-Yang Duh,

Electron Kebebew. - 2nd ed.
p. . crn.
Includes bibliographical references and index.
ISBN 0-7216-0139-1
I. Endocrine glands-Surgery. 2. Endocrine glands-Diseases. I. Clark, Orlo H. II. Duh,
Quan-Yang. III. Kebebew, Electron.
[DNLM: 1. Endocrine System Diseases-surgery. 2. Endocrine Glands-surgery. WK
140 T355 2006]
RD599.T492006
617.4' 4-dc22 2005042824

Acquisitions Editor: Judith Fletcher

Publishing Services Manager: Tina Rebane
Project Manager: Norm Stellander
Design Manager: Gene Harris

Printed in the United States of America

Last digit is the print number: 9 8 7 6 5 4 3 2 1

 Dedication

We would like to dedicate this book to our wives, Carol, Ann, and Tida, and families, and to
Ms. Kate Poole. Their wonderful support helped to make this book possible.
Claudette Abela-Forman EK, MD Anders O. J. Bergenfelz, MD, PhD
Assistant Professor, Department of Ophthalmology, Associate Professor, Lund University; Consultant Surgeon,
Medical University of Vienna; Senior Resident, General Department of Surgery, University Hospital,
Hospital of Vienna, Vienna, Austria Lund, Sweden
Metabolic Complications of Primary Hyperparathyroidism Surgical Approach to Primary Hyperparathyroidism
(Unilateral Approach)
Bo Ahren, MD, PhD
Professor, Department of Medicine, Lund University, Piero Berti, MD
Lund, Sweden Professor of Surgery, University of Pisa; Assistant,
Pancreatic Endocrine Physiology S. Chiara Hospital, Pisa, Italy
Minimally Invasive Parathyroid Surgery
Goran Akerstrom, MD, PhD
Professor of Surgery, Uppsala University; Professor of Michael Sean Boger, MD, PharmD
Surgery and Chief of Endocrine Surgery, Department of House Officer, Department of Internal Medicine,
Surgical Sciences, University Hospital, Uppsala, Sweden Wake Forest University Baptist Medical Center,
Natural History of Untreated Primary Winston-Salem, North Carolina
Hyperparathyroidism Graves' and Plummer's Diseases: Medical and Surgical
Management
Maha AI-Fehaily, MD
Associate Consultant, Breast and Endocrine Surgery, H. Jaap Bonjer, MD, PhD
King Faisal Specialist Hospital and Research Centre, Professor of Surgery, Dalhousie University; Director of
Department of Surgery, Riyadh, Saudi Arabia Minimally Invasive Surgery, Queen Elizabeth II Health
Sporadic Nontoxic Goiter Sciences Center, Halifax, Nova Scotia, Canada
Technique of Parathyroidectomy
Saif AI-Sobhi, MD, FRCS (Glas), ABIS
Chairman, Department of Surgery, King Faisal Specialist Bert A. Bonsing, MD, PhD
Hospital and Research Centre, Riyadh, Saudi Arabia Staff Surgeon, Department of Surgery, Leiden University
Parathyroid Hyperplasia: Parathyroidectomy Medical Center, Leiden, Germany
Occurrence and Prevention of Complications in Thyroid
Ahmad Assalia, MD Surgery
Deputy Director, Department of Surgery, Rambam Medical
Center, Haifa, Israel Michael Brauckhoff, MD
Laparoscopic Adrenalectomy Department of General, Visceral, and Vascular Surgery,
University of Halle, Halle, Germany
Jon Armstrong, MD Surgical Management ofAdvanced Thyroid Cancer
Clinical Instructor, University of Perth, Royal Perth Invading the Aerodigestive Tract
Hospital; Senior Surgeon, General and Endocrine
Surgery, Royal Perth Hospital, Perth, Western Australia, James D. Brierley, MB BS, MRCP, FRCP, FRCP (C)
Australia Associate Professor, Department of Radiation Oncology,
Adrenocortical Carcinoma: Nonfunctioning and University of Toronto, Toronto; Staff Radiation
Functioning Oncologist, Princess Margaret Hospital, University
Health Network, Toronto, Ontario, Canada
Sylvia L. Asa, MD, PhD Anaplastic Carcinoma of the Thyroid Gland
Professor, Department of Laboratory Medicine and
Pathobiology, University of Toronto, Toronto; Hajo A. Bruining, MD, PhD
Pathologist-in-Chief, University Health Network, and Emeritus Professor of Surgery, Erasmus University,
Medical Director, Toronto Medical Laboratories, Rotterdam, The Netherlands
Toronto, Ontario, Canada Technique of Parathyroidectomy
Anaplastic Carcinoma of the Thyroid Gland

v
vi - - Contributors

Laurent Brunaud, MD, PhD Michael J. Demeure, MD

Professor of Surgery, University of Nancy; Staff Surgeon, Chief, Section of General Surgery, Professor of Surgery,
Department of General and Endocrine Surgery, Arizona Health Sciences Center, Tucson, Arizona
Chu Nancy-Brabois, Nancy, France Mechanisms and Regulation of Invasion in Thyroid Cancer
Comparative Genomic Hybridization in Thyroid
Neoplasms; Neuroendocrine Tumors Gerard M. Doherty, MD
M. W. Thompson Professor of Surgery, University of
Blake Cady, MD Michigan, Ann Arbor, Michigan
Professor of Surgery, Brown Medical School; Interim Follicular Neoplasms of the Thyroid
Director, Comprehensive Breast Center,
Rhode Island Hospital, Providence, Rhode Island Henning Dralle MD
Predictors of Thyroid Tumor Aggressiveness Head, Department of General, Visceral, and Vascular
Surgery, University of Halle, Halle, Germany
Denise M. Carneiro-Pia, MD Surgical Management ofAdvanced Thyroid Cancer
Fellow, Department of Endocrine Surgery, University of Invading the Aerodigestive Tract
Miami/Jackson Memorial Center, Miami, Florida
Intraoperative Parathyroid Hormone Assay as a Surgical Quan-Yang Duh, MD
Adjunct in Patients with Sporadic Primary Professor of Surgery, University of California,
Hyperparathyroidism San Francisco, School of Medicine, San Francisco,
California
Herbert Chen, MD, FACS Potentially New Therapies in Thyroid Cancer;
Chief of Endocrine Surgery, and Assistant Professor of Surgical Approach to Primary Hyperparathyroidism
Surgery, University of Wisconsin, Madison, Wisconsin (Bilateral Approach)
Hiirthle Cell Adenoma and Carcinoma
Erol Duren, MD
Polly S-Y Cheung, MB BS (HK) Professor Emeritus, Department of Surgery, University of
Consultant Surgeon, Hong Kong Sanatorium and Hospital, Istanbul, Cerrahpasa Medical School;
Happy Valley, Hong Kong Medical Director and Chief of Surgery, Istanbul German
Medical and Surgical Treatment of Endemic Goiter Hospital, Istanbul, Turkey
Recurrent Thyroid Cancer
Orlo H. Clark, MD
Professor of Surgery, Department of Surgery, University of Mete Duren, MD
California, San Francisco, School of Medicine, Professor, Department of Surgery, University of Istanbul,
San Francisco, California Cerrahpasa Medical School, Istanbul, Turkey
Sporadic Nontoxic Goiter; Thyroiditis; Papillary Thyroid Recurrent Thyroid Cancer
Carcinoma: Rationale for Total Thyroidectomy;
Potentially New Therapies in Thyroid Cancer; Diagnosis Kathryn L. Edmiston, MD
of Primary Hyperparathyroidism and Indications for Assistant Professor of Medicine, Associate Director,
Parathyroidectomy; Parathyroid Hyperplasia: Breast Center, University of Massachusetts Medical
Parathyroidectomy Center, Boston, Massachusetts
Chemotherapy for Unresectable Endcorine Neoplasms
Roderick Clifton-Bligh, MBBS, PhD, FRACP
Honorary Senior Lecturer in Medicine, University of E. Christopher Ellison, MD
Sydney; Staff Specialist in Endocrinology, Royal North Professor and Chair, Department of Surgery, The Ohio
Shore Hospital, Sydney, New South Wales, Australia State University College of Medicine and Public Health,
Thyroid Physiology Columbus, Ohio
Multiple Endocrine Neoplasia Type 2B
Alan P. B. Dackiw, MD, PhD
Assistant Professor of Surgery, Johns Hopkins University, Gennaro Favia, MD
Baltimore, Maryland Professor of Surgery and Head, Endocrine Surgery Unit,
Transplantation of Endocrine Cells and Tissues Department of Surgical and Gastroenterological
Sciences, University of Padua, School of Medicine,
Leigh Delbridge, MD, FRACS Padova, Italy
Professor of Surgery, University of Sydney; Head, Cushing's Syndrome
Department of Surgery, Royal North Shore Hospital,
Sydney, New South Wales, Australia
Thyroid Physiology
 Contributors - - vii

Volker Fendrich, MD Oliver Gimm, MD

Resident in Surgery, Philipps University; Resident in the Department of General, Visceral, and Vascular Surgery,
Department of Visceral, Thoracic, and Vascular Surgery, Martin Luther University of Halle-Wittenberg, Halle,
Klinikum Der Philipps-Universitat, Marburg, Germany Germany
Localization of Endocrine Pancreatic Tumors Surgical Management ofAdvanced Thyroid Cancer
Invading the Aerodigestive Tract
Douglas L. Fraker, MD
Jonathan Rhoads Associate Professor of Surgery; Victor Gorelev, MD
Vice Chairman, Clinical Affairs, and Director, General Professor of Surgery, Heinrich Heine University,
Surgery, University of Pennsylvania, Philadelphia, DUsseldorf, Germany
Pennsylvania Oncogenes in Thyroid Tumors
Factors That Predispose to Thyroid Neoplasia
Peter E. Goretzki, MD
John R. Frandon, BSc, MD, FRCSt Professor of Surgery, Heinrich Heine University,
Formerly Professor of Surgery, University of Bristol, DUsseldorf, Germany
United Kingdom Oncogenes in Thyroid Tumors
Surgical Embryology and Anatomy of the Adrenal Glands
Clive S. Grant, MD
Yoshihide Fujimoto, MD, PhD Professor of Surgery, Mayo Clinic, Rochester, Minnesota
Former Professor of Surgery, Department of Endocrine Pheochromocytoma
Surgery, Tokyo Women's Medical University, Tokyo;
Adviser of the Hospital and Director, Division of Staffan Grandal, MD, PhD
Thyroid-Endocrine Surgery, Cancer Institute Hospital, Associate Professor of Surgery, Karolinska Institutet;
Tokyo, Japan Consultant, Department of Surgery, Danderyds Hospital,
Papillary Thyroid Carcinoma: Rationale for Stockholm, Sweden
Hemithyroidectomy Adrenal Physiology

Shuji Fukata, MD Bertil Hamberger, MD, PhD

Chief of Internal Medicine, Kuma Hospital, Kobe, Japan Professor of Surgery, Department of Surgical Sciences,
Hypothyroidism Karolinska Institutet; Consultant; Department of
Surgery, Karolinska Hospital, Stockholm, Sweden
Michel Gagner, MD, FRCS, FACS Adrenal Physiology
Professor of Surgery, Weill Medical College of Cornell
University; Chief, Laparoscopy and Bariatric Surgery, J. F. Hamming, MD, PhD
Department of Surgery, New York-Presbyterian Hospital, Surgeon, St. Elisabeth Hospital, Tilburg; The Netherlands
New York, New York Management of Regional Lymph Nodes in Papillary,
Laparoscopic Adrenalectomy Follicular, and Medullary Thyroid Cancer

Armando Gamboa-Dominguez, MD, PhD Jay K. Harness, MD

Associate Professor of Pathology, Facultad de Medicina, Medical Director, St. Joseph Hospital Comprehensive
Universidad Nacional Aut6noma de Mexico; Breast Center, Orange, California
Senior Pathologist, Instituto Nacional de Ciencias Childhood Thyroid Carcinoma
Medicas y Nutrici6n Salvador Zubiran, Mexico City,
Mexico Susannah E. Harte, MD, MRCPI
Parathyroid Embryology, Anatomy, and Pathology University College, Dublin, Ireland
Use and Abuse of Thyroid-Stimulating Hormone
Helene Gilbelin, MD Suppressive Therapy in Patients with Nodular Goiter
Consultant Surgeon, Endocrine Surgery, Jean Bernard and Benign or Malignant Thyroid Neoplasms
Hospital, Poitiers, France
Familial Hyperparathyroidism in Multiple Endocrine Nils-Erik Heldin, PhD
Neoplasia Syndromes Associate Professor in Experimental Pathology, University,
Hospital, Uppsala, Sweden
Glenn Gibson, BA Growth Factor, Thyroid Hyperplasia, and Neoplasia
Senior Scientist, Pfizer Global Research and Development,
Ann Arbor; Michigan Jean-Francois Henry, MD
Cryopreservation of Parathyroid Tissue Professor of Surgery, University of Marseilles; Chief,
Department of General and Endocrine Surgery,
University Hospital La Timone, Marseilles, France
Surgical Anatomy and Embryology of the Thyroid and
Parathyroid Glands and Recurrent and External
tDeceased Laryngeal Nerves; Endoscopic Parathyroidectomy
viii - - Contributors

Miguel F. Herrera, MD, PhD Electron Kebebew, MD

Associate Professor of Surgery, Facultad de Medicina, Assistant Professor of Surgery, University of California,
Universidad Veracruzana; Staff Surgeon, Instituto San Francisco/Mt, Zion Medical Center, San Francisco,
Nacional de Ciencias Medicas y Nutrici6n Salvador California
Zubiran, Mexico City, Mexico Thyroid Oncogenesis
Parathyroid Embryology, Anatomy, and Pathology
Rachel R. Kelz, MD
Shih-ming Huang, MD Assistant Professor of Clinical Surgery, University of
Professor, Department of Surgery, Buddhist Tzu-Chi Pennsylvania, Philadelphia, Pennsylvania
University; Professor and Consultant Surgeon, Buddhist Factors that Predispose to Thyroid Neoplasia
Tzu-Chi General Hospital, Hualien, Taiwan
Familial Hyperparathyroidism Job Kievit, MD, PhD
Professor of Clinical Decision Analysis and Associate
Maurizio Iacobone, MD Professor of Surgery, Leiden University Medical Center;
Assistant Professor, Clinical Research, University of Chief, Section of EndocrinelHead and Neck Surgery,
Padua, School of Medicine; Endocrine Surgery Unit, Department of Surgery, Leiden University Medical
Department of General and Gastroenterological Center, Leiden, Germany
Sciences, University of Padua, Italy Occurrence and Prevention of Complications in
Cushing's Syndrome Thyroid Surgery

Masatoshi Iihara, MD Barbara K. Kinder, MD

Assistant Professor, Department of Endocrine Surgery, William H. Carmalt Professor of Surgery, Yale University,
Tokyo Women's Medical University; Assistant Professor, School of Medicine; Attending Surgeon, Yale-New
Department of Endocrine Surgery, Tokyo Women's Haven Hospital, New Haven, Connecticut
Medical University Hospital, Shinjuku-ku, Tokyo, Japan Endocrine Emergencies: Hypoglycemic and
Hyperaldosteronism Hyperglycemic Crises

Silvio E. Inzucchi, MD Jean-Louis Kraimps, MD

Professor of Medicine, Section of Endocrinology, Professor, Poitiers University Medical School; Professor of
Yale University School of Medicine; Director, General Surgery, Jean Bernard Hospital, Poitiers, France
Yale Diabetes Center, Yale-New Haven Hospital, Familial Hyperparathyroidism in Multiple Endocrine
New Haven, Connecticut Neoplasia Syndromes
Endocrine Emergencies: Hypoglycemic and
Hyperglycemic Crises Kanji Kuma, MD
Honorary Director, Kuma Hospital, Kobe, Japan
George L. Irvin III, MD Hypothyroidism
Professor of Surgery, University of Miami School of
Medicine, Miami, Florida Geeta Lal, MD, MSc, FRCS(C)
Intraoperative Parathyroid Hormone Assay as a Surgical Assistant Professor of Surgery, University of Iowa; Staff
Adjunct in Patients with Sporadic Primary Surgeon, Department of Surgery, University of Iowa
Hyperparathyroidism Hospitals and Clinics, Iowa City, Iowa
Thyroiditis; Diagnosis of Primary Hyperparathyroidism
Yukio Ito, MD and Indications for Parathyroidectomy
Associate Professor, Department of Endocrine Surgery,
Tokyo Women's Medical University; Associate Anne C. Larkin, MD
Professor, Department of Endocrine Surgery, Tokyo Director of Undergraduate Surgical Education, Department
Women's Medical University Hospital, Shinjuku-ku, of Surgery, University of Massachusetts Medical School,
Tokyo, Japan Worcester, Massachusetts
Hyperaldosteronism Chemotherapy for Unresectable Endocrine Neoplasms

Suzanne Jan de Beur, MD Chen-Hsen Lee, MD

Director, Division of Endocrinology, Johns Hopkins Professor of Surgery, National Yang-Ming University; Team
Bayview Medical Center, Baltimore, Maryland Leader of Endocrine Surgery and Vice Superintendent,
Hypoparathyroidism and Pseudohypoparathyroidism Taipei Veterans General Hospital, Taipei, Taiwan
Thyroid Emergencies: Thyroid Storm and Myxedema Coma
Edwin L. Kaplan, MD
Professor of Surgery, The University of Chicago, Pritzker Sten Lennquist, MD, PhD
School of Medicine; Attending Physician, The Professor Emeritus, University of Linkoping; Former
University of Chicago Hospitals, Chicago, Illinois Chairman, Department of Surgery, University Hospital,
Insulinomas Linkoping, Sweden
Thyroidectomy
 Contributors - - ix

Hong-Da Lin, MD Christopher R. McHenry, MD

Clinical Professor, Taipei Medical University, School of Professor of Surgery, Case Western Reserve University
Medicine; Chief, Division of Endocrinology and School of Medicine; Vice Chairman, Department of
Metabolism, Taipei Veterans General Hospital, Surgery, and Director, Division of General Surgery,
Taipei, Taiwan MetroHealth Medical Center, Cleveland, Ohio
Thyroid Emergencies: Thyroid Storm and Myxedema Coma Anatomy and Embryology of the Pancreas

Dimitrios A. Linos, MD Paolo Miccoli, MD

Associate Professor of Surgery, Athens Medical School, Professor of Surgery, and Chairman, Department of
and Director of First Surgical Clinic, Hygeia Hospital Surgery, Universita Studi di Pisa, Pisa, Italy
Athens, Greece; Lecturer in Surgery, Harvard Medical Papillary and Follicular Carcinoma: Surgical and
School, and Consultant in Surgery, Massachusetts Radioiodine Treatment of Distant Metastases; Minimally
General Hospital, Boston, Massachusetts Invasive Parathyroid Surgery
Clinically Inapparent Adrenal Mass (Incidentaloma or
Adrenaloma) Raducu Mihai, MD, PhD, MRCS
Lecturer in Surgery, University of Bristol; Specialist
Chung Yau Lo, MB BS(HK), MS(HK), Registrar in Endocrine Surgery, Bristol Royal Infirmary,
FRCS(Edin), FACS Bristol, United Kingdom
Associate Professor, Faculty of Medicine, The University Surgical Embryology and Anatomy of the Adrenal Glands
of Hong Kong, Queen Mary Hospital; Associate
Professor and Chief of Endocrine Surgery, Department Craig A. Miller, MD
of Surgery, University of Hong Kong Medical Center, Director of Vascular Services, St. Joseph Hospital,
Queen Mary Hospital, Hong Kong Kokomo, Indiana
Parathyroid Reoperations Multiple Endocrine Neoplasia Type 2B

Franco Lumachi, MD Daishu Miura, MD

Assistant Professor, Clinical Research, University of Staff, Department of Endocrine Surgery, Toranomon
Padua, School of Medicine; Endocrine Surgery Unit, Hospital, Tokyo, Japan
Department of Surgical and Gastroenterological Comparative Genomic Hybridization in Thyroid
Sciences, University of Padua, School of Medicine, Neoplasms
Padova, Italy
Cushing's Syndrome Jeffery F. Moley, MD
Associate Professor of Surgery, Washington University
Ewa Lundgren, MD, PhD School of Medicine; Associate Chief of Surgery,
Associate Professor, Uppsala University, Medical Faculty; St. Louis Veterans Administration Medical Center,
Consultant and Head of the Surgery Department, St. Louis, Missouri
Institution of Surgical Sciences, University Hospital, Medullary Thyroid Carcinoma
Uppsala, Sweden
Natural History of Untreated Primary Jack M. Monchik; MD, FACS
Hyperparathyroidism Clinical Professor of Surgery, Brown University School of
Medicine, Chief, Endocrine Surgery, Rhode Island
Andreas Machens, MD Hospital, Providence, Rhode Island
Department of General, Visceral, and Vascular Surgery, Normocalcemic Hyperparathyroidism
University of Halle, Halle, Germany
Surgical Management ofAdvanced Thyroid Cancer Bruno Niederle, MD
Invading the Aerodigestive Tract Professor of Surgery, Section of Endocrine Surgery,
Division of General Surgery, Department of Surgery,
Lloyd A. Mack, MD, FRCSC Medical University of Vienna; Chief, Endocrine Surgery,
Assistant Professor, Department of Surgery and Oncology, General Hospital of Vienna, Vienna, Austria
Division of General Surgery, University of Calgary Metabolic Complications of Primary Hyperparathyroidism
Faculty of Medicine, Calgary, Alberta, Canada
Unusual Thyroid Cancers, Lymphoma, and Metastases to Ronald H. Nishiyama, MD
the Thyroid Chief Emeritus, Department of Pathology, Maine Medical
Center, Portland, Maine
Paul R. Maddox, BSc, MCh, FRCS(Ed), Pathology of Tumors of the Thyroid Gland
FRCS(Eng)
Consultant Surgeon, Royal United Hospital, Bath, Shiro Noguchi, MD, PhD, FJCS, FACE
England, United Kingdom Chief Executive Officer, Noguchi Thyroid Clinic and
Approach to Thyroid Nodules Hospital Foundation, Beppu, Oita, Japan
Localization Tests in Patients with Thyroid Cancer
x - - Contributors

Jeffrey A. Norton, MD Janice L. Pasieka, MD

Professor of Surgery, Stanford University Medical Center; Clinical Professor of Surgery and Oncology, Faculty of
Chief of Surgical Oncology, Stanford University, Medicine, Department of Surgery, University of
Department of Surgery, Stanford, California Calgary; Regional Division Chief, Division of General
Somatostatinoma and Rare Pancreatic Endocrine Tumors Surgery, Calgary Health Region and University of
Calgary, Foothills Medical Center, Calgary, Alberta,
Patricia J. Numann, MD Canada
The Lloyd S. Rogers Professor of Surgery, SUNY Unusual Thyroid Cancers, Lymphoma, and Metastases to
Distinguished Teaching Professor, and SUNY the Thyroid; Asymptomatic Primary
Distinguished Service Professor, State University of Hyperparathyroidism
New York, Upstate Medical University; Medical
Director, University Hospital, Syracuse, New York Fran~ois N. Pattou, MD
Addison's Disease and Acute Adrenal Hemorrhage Associate Professor of Surgery, Medical School of Lille;
Senior Surgeon, Department of General and Endocrine
Takao Obara, MD, PhD Surgery, Lille University Hospital-Huriez, Lille,
Professor and Chief, Department of Endocrine Surgery, France
Tokyo Women's Medical University, Tokyo; Director, Advenocortical Carcinoma: Nonfunctioning and
Institute of Clinical Endocrinology, Tokyo Women's Functioning
Medical University Hospital, Tokyo, Japan
Papillary Thyroid Carcinoma: Rationale for Nilima A. Patwardhan, MD
Hemithyroidectomy; Hyperaldosteronism Professor of Surgery, University of Massachusetts
Medical Center, Worcester, Massachusetts
Niall O'Higgins, MCh, FRCSI, FRCS(Edin), Chemotherapy for Unresectable Endocrine Neoplasms
FRCS(Eng)
Professor and Head, Department of Surgery, University Nancy Dugal Perrier, MD FACS
College, Dublin; Professor of Surgery, St. Vincent's Associate Professor of Surgery, Department of Surgical
University Hospital, Dublin, Ireland Oncology, University of Texas M.D. Anderson Cancer
Use and Abuse of Thyroid-Stimulating Hormone Center, Houston, Texas
Suppressive Therapy in Patients with Nodular Goiter Graves' and Plummer's Diseases: Medical and Surgical
and Benign or Malignant Thyroid Neoplasms Management

Takahiro Okamoto, MD, PhD Gerhard Prager, MD

Assistant Professor, Department of Endocrine Surgery, Assistant Professor, Section of Endocrine Surgery, Division
Tokyo Women's Medical University, Tokyo, Japan of General Surgery, Department of Surgery, Medical
Papillary Thyroid Carcinoma: Rationale for University of Vienna; Senior Resident, General Hospital
Hemithyroidectomy of Vienna, Vienna, Australia
Metabolic Complications of Primary Hyperparathyroidism
Furio Pacini, MD
Professor of Endocrinology, Universita di Siena, Siena Richard A. Prinz, MD
Italy Helen Shedd Keith Professor and Chairman, Department of
Papillary and Follicular Carcinoma: Surgical and General Surgery, Rush University; Chairman,
Radioiodine Treatment of Distant Metastases Department of General Surgery, Rush University
Medical Center, Chicago, Illinois
Kevin Packman, MD Open Operative Approaches to the Adrenal Gland
Department of Surgery, Froedtert Memorial Lutheran
Hospital and Medical College of Wisconsin, Milwaukee, Charles A. G. Proye, MD
Wisconsin Professor and Chairman of Surgery, Medical School of
Mechanisms and Regulation of Invasion in Thyroid Cancer Lille; Head of the Department of General and Endocrine
Surgery, Lille University Hospital-Huriez, Lille, France
P. Parrilla, MD Adenocortical Carcinoma: Nonfunctioning and Functioning
Professor of Surgery, Department of Surgery, School of
Medicine, University of Murcia; Chairman, Department Roderick M. Quiros, MD
of General Surgery, Virgen de la Arrixaca University General Surgery Resident, Rush University Medical
Hospital, Murcia, Spain Center, Chicago, Illinois
Localization Studies in Persistent or Recurrent Open Operative Approaches to the Adrenal Gland
Hyperparathyroidism
Jonas Rastad, MD, PhD
Jin-Woo Park, MD, PhD Associate Professor, Department of Surgery,
Associate Professor, College of Medicine, Chungbuk Uppsala University Hospital, Uppsala, Sweden
National University, Cheongju, Korea Parathyroid Hormone: Regulation of Secretion and
Potentially New Therapies in Thyroid Cancer Laboratory Determination
 Contributors - - xi

Peter Ridefelt, MD, PhD Andrew Saxe, MD

Associate Professor, Department of Surgery, Uppsala Associate Program Director, Michigan State University,
University Hospital, Uppsala, Sweden East Lansing; Director, Surgical Education, McLaren
Parathyroid Hormone: Regulation of Secretion and Regional Medical Center, Flint, Michigan
Laboratory Determination Cryopreservation of Parathyroid Tissue

Jose M. Rodriguez, MD Frederic Sebag, MD

Professor of Surgery, Department of Surgery, School of Medical School, Mediterranean University; Attending
Medicine, University of Murcia; Endocrine Surgery Surgeon in Endocrine Surgery, Department of Endocrine
Unit, Department of Surgery, Virgen de la Arrixaca, Surgery, University Hospitalla Timone, Marseilles,
II University Hospital, Murcia, Spain France
Localization Studies in Persistent or Recurrent Endoscopic Parathyroidectomy
Hyperparathyroidism
Wen T. Shen, MD
Hans-Dietrich Roeher, MD Fellow, Endocrine Surgical Oncology Program,
Professor of Surgery, Heinrich Heine University, Department of Surgery, University of California,
Dusseldorf, Germany San Francisco, San Francisco, California
Oncogenes in Thyroid Tumors; Neuroendocrine Tumors Parathyroid Hormone: Regulation of Secretion and
Irving B. Rosen, MD, FRCS(C) Laboratory Determination
Professor, Department of Surgery, University of Toronto,
Toronto; Attending Surgeon, Mt. Sinai Hospital, Nina Shervin, MD
Toronto, Ontario, Canada Resident in Surgery, Harvard Combined Orthopaedic
Anaplastic Carcinoma of the Thyroid Gland Residency Program, Massachusetts General Hospital,
Boston, Massachusetts
Matthias Rothmund, MD Medullary Thyroid Carcinoma
Professor of Surgery, Philipps University; Professor of
Surgery and Chairman of the Department of Visceral, Mauricio Sierra, MD
Thoracic, and Vascular Surgery, Klinikum der Fellow in Endocrine Surgery, Jean Bernard Hospital,
Philipps-Universitat, Marburg, Germany Poitiers, France
Adrenal Imaging Procedures; Localization of Endocrine Familial Hyperparathyroidism in Multiple Endocrine
Pancreatic Tumors Neoplasia Syndromes

J. A. Roukema, MD, PhD Dietmar Simon, MD

Surgeon, St. Elisabeth Hospital, Tilburg, The Netherlands Professor of Surgery, Heinrich Heine University,
Management of Regional Lymph Nodes in Papillary, Dusseldorf, Germany
Follicular, and Medullary Thyroid Cancer Neuroendocrine Tumors; Oncogenes in Thyroid Tumors

Mary Ruppe, MD Antonio Sitges-Serra, MD

Senior Fellow, Division of Endocrinology, Johns Hopkins Professor of Surgery, Universedad Aut6noma de
Bayview Medical Center, Baltimore, Maryland Barcelona; Head, Department of Surgery, Hospital del
Hypoparathyroidism and Pseudohypoparathyroidism Mar, Barcelona, Spain
Surgical Management of Recurrent and Intrathoracic
David E. Sahar, MD Goiters; Metabolic Complications of Secondary
Resident, University of California San Francisco-East Bay Hyperparathyroidism; Surgical Approach to Secondary
Program, San Francisco, California Hyperparathyroidism
Childhood Thyroid Carcinoma
Allan E. Siperstein, MD
Juan J. Sancho, MD
Professor of Surgery and Section Head, Endocrine Surgery,
Associate Professor, Universidad Aut6noma de Barcelona;
The Cleveland Clinic Foundation, Cleveland, Ohio
Staff Surgeon; Hospital del Mar, Barcelona, Spain
Signal Transduction in Thyroid Neoplasms
Surgical Management ofRecurrent and Intrathoracic
Goiters; Metabolic Complications of Secondary
Staffan Smeds, MD, PhD
Hyperparathyroidism; Surgical Approach to Secondary
Professor of Surgery, University Hospital, Linkoping,
Hyperparathyroidism
Sweden
Kerstin Sandelin, MD, PhD Growth Factor, Thyroid Hyperplasia, and Neoplasia
Associate Professor of Surgery, Department of Surgical
Sciences, Korolinska Institutet, Stockholm; Senior Staff Ilfet Songun, MD, PhD
Surgeon, Karolinska University Hospital, Solna, Surgeon, University Hospital, Maastricht,
Stockholm, Sweden The Netherlands
Parathyroid Carcinoma Occurrence and Prevention of Complications in
Thyroid Surgery
xii - - Contributors

Maria Sorhede-Winzell, PhD John A. van Heerden, MB, ChB, MS(Surg) (Minn),
Department of Medicine, Lund University, Lund, Sweden FRCS (C), FACS, Hon FCM(SA), Hon FRCS(Edin),
Pancreatic Endocrine Physiology FRCPS (Glasg)
Fred C. Anderson Professor of Surgery, Mayo Graduate
Gordon J. Strewler, MD School; Consultant in General Surgery, Mayo Clinic,
Professor of Medicine, Harvard Medical School; Vice Rochester, Minnesota
Chairman, Department of Medicine, Brigham and Parathyroid Reoperations
Women's Hospital; Chief of Medical Service, Brockton/
West Roxburg, Veterans Administration Medical Center, Cornelis J. H. van de Velde, MD, PhD
Boston, Massachusetts Professor of Surgery, Leiden University Medical Center,
Hypercalcemia of Malignancy and Parathyroid Leiden, Germany
Hormone-Related Protein Occurrence and Prevention of Complications in
Thyroid Surgery
Masahiro Sugawara, MD
Professor of Medicine, University of California, Los Angeles, Nobuyuki Wada, MD, PhD
School of Medicine; Staff Physician, Greater Los Angeles Assistant Professor, Department of Surgery, Yokohama City
VA Medical Center, Los Angeles, California University School of Medicine, Yokohama City, Japan
Hypothyroidism Comparative Genomic Hybridization in Thyroid Neoplasms
Hiroshi Takami, MD
Jeffrey D. Wayne, MD
Professor of Surgery, Teiko University School of Medicine,
Assistant Professor of Surgery, Northwestern University,
Tokyo,Japan
Feinberg School of Medicine; Attending Physician,
Hypercalcemic Crisis
Northwestern Memorial Hospital, Chicago, Illinois
Serdar T. Tezelman, MD Insulinomas
Professor of Surgery, Department of Surgery, Istanbul
Faculty of Medicine, Istanbul University; Attending Malcolm H. Wheeler, MD, FRCS
Surgeon, International Hospital, Istanbul, Turkey Professor of Surgery, University Hospital of Wales,
Signal Transduction in Thyroid Neoplasms Cardiff, Wales, United Kingdom
Approach to Thyroid Nodules
Geoffrey B. Thompson, MD
Professor of Surgery, Mayo Graduate School; Consultant, Scott M. Wilhelm, MD
Department of Surgery, Division of Gastroenterologic Assistant Professor of Surgery, University Hospital of
and General Surgery, Mayo Clinic, Saint Mary's and Cleveland, Case Western Reserve University; Staff
Rochester Methodist Hospitals, Rochester, Minnesota Surgeon, University Hospitals of Cleveland, Cleveland,
Multiple Endocrine Neoplasia Type 1 Ohio
Open Operative Approaches to the Adrenal Gland
Norman W. Thompson, MD
Emeritus Professor of Surgery, University of Michigan, Stuart D. Wilson, MD
Ann Arbor, Michigan Professor and Chief, Division of
Pancreatic Surgery for Endocrine Tumors PancreatobiliarylEndocrine Surgery, Medical College of
Wisconsin; Senior Attending Surgeon, Froedtert
Sten A. G. Tibblin, MD, PhDt Memorial Lutheran Hospital, Milwaukee, Wisconsin
Formerly Associate Professor and Consultant Surgeon, Gastrinoma
Department of Surgery, University Hospital, Lund, Sweden
Surgical Approach to Primary Hyperthyroidism Michael W. Yeh, MD
(Unilateral Approach) Fellow, University of California, San Francisco,
San Francisco, California; Endocrine Surgical Unit,
Lars-Erik Tisell, MD, PhD
Royal North Shore Hospital, St. Leonards,
Retired Chief of Endocrine Surgery, Department of Surgery,
New South Wales, Australia
Sahlgrenska University Hospital, Sahlgrenska, Sweden
Mechanisms and Regulation of Invasion in Thyroid Cancer
Natural History of Treated Primary Hyperparathyroidism

Robert Udelsman, MD, MBA, FACS William F. Young, Jr, MD, MSc
Lampman Professor of Surgery and Oncology, and Professor of Medicine, Mayo Clinic College of Medicine;
Chairman, Department of Surgery, Yale University Consultant, Division of Endocrinology and Metabolism,
School of Medicine; Chief of Surgery, Mayo Clinic, Rochester, Minnesota
Yale New Haven Hospital, New Haven, Connecticut Multiple Endocrine Neoplasia Type 1
Hiirthle Cell Adenoma and Carcinoma
Rasa Zarnegar, MS
Surgical Resident, Case Western Reserve University
Cleveland, Ohio
tDeceased Sodium-Iodide Symporter and Radioactive Iodine Therapy
 Contributors - - xiii

Andrew P. Zbar, MB, BS Andreas Zielke, MD

University of the West Indies, Queen Elizabeth Hospital, Department of Surgery, Endocrine Research Group,
St. Michael, Barbados Philipps University, Marburg, Germany
Use and Abuse of Thyroid-Stimulating Hormone Adrenal Imaging Procedures
Suppressive Therapy in Patients with Nodular Goiter
and Benign or Malignant Thyroid Neoplasms

Martha A. Zeiger, MD
Associate Professor of Surgery, Division of Endocrine and
Oncologic Surgery, Johns Hopkins Medical Institutions,
Baltimore, Maryland
Hypoparathyroidism and Pseudohypoparathyroidism;
Transplantation of Endocrine Cells and Tissues
Since the first edition of the Textbook of Endocrine Surgery associated with ret/PTC rearrangements and other papillary
there have been considerable changes in the clinical man- thyroid cancers with BRAF mutations, whereas follicular
agement of patients with endocrine surgical problems, as cancers are more often associated with PAX-S/PPARy and
well as advances in basic science regarding endocrine ras mutations.
neoplasms. Many colleagues have asked Drs. Duh and Clark Since the Chemobyl nuclear accident in 1986, considerably
whether another edition will be published because of numer- more information has become available relating to the
ous recent changes in endocrine surgery. Major changes association of radiation exposure and thyroid cancer. Many
have occurred regarding the indications for parathyroidec- other advances or consensus of opinion have also become
tomy in patients with primary hyperparathyroidism based on available regarding the diagnosis, localization, and treat-
the natural history of the disease. The surgical approach for ment of endocrine neoplasms, including endocrine tumors
patients with primary hyperparathyroidism has also changed of the pancreas.
as more surgeonsare now recommending a selective approach New or revised areas in the second edition of Textbook
rather than a bilateral approach. Much of this change is due to of Endocrine Surgery include: (l) recent advances in the
better preoperative localization studies and the use of intra- etiology and molecular biology of endocrine neoplasms;
operative parathyroid hormone assays to determine when all (2) methods used to diagnose patients with sporadic and
abnormal parathyroid tissue has been removed. Some familial thyroid cancers and the risks and benefits of prophy-
experts are also recommending a minimally invasive lactic operations; (3) the association of low-dose therapeutic
approach via small == 2.S-cm incisions or by using an endo- radiation, RET/PTC rearrangements, and surgical manage-
scopic approach with I.S-cm incisions for patients with ment of thyroid tumors; (4) current information regarding the
primary hyperparathyroidism. adverse effects of primary hyperparathyroidism and related
Substantial changes have also occurred regarding indica- symptoms, associated conditions, and survival, as well as
tions for adrenalectomy for patients with incidentally discov- the indications for parathyroidectomy (this will include the
ered adrenal neoplasms. More accurate localization studies usefulness of the follow-up information regarding the NIH
and improved testing have made the diagnosis easier and consensus criteria and newer studies regarding quality of life
tumor identification more precise. Most endocrine surgeons improvement after parathyroidectomy); (5) the changing
are now recommending laparoscopic removal of non-malig- selective surgical approach for patients with primary hyper-
nant-appearing adrenal tumors under 6 em in maximal parathyroidism based on preoperative localization tests and
diameter. Such treatment has dramatically reduced the dura- intraoperative PTH testing; (6) the indications for operations
tion of hospitalization and has also increased the referral of for patients with incidentally discovered adrenal neoplasms;
such patients to endocrine surgical units that are proficient and (7) the use of laparoscopic adrenalectomy to remove
in laparoscopic operations. most adrenal tumors under 6 em in maximal diameter.
There have been numerous other advances in using In summary, during the past several years there have
genetic testing to diagnose patients with multiple endocrine been improved methods for diagnosing and treating patients
neoplasia types I and II. Children who are ret oncogene pos- with endocrine neoplasms, including screening for familial
itive usually receive prophylactic thyroidectomy before age disease, more precise diagnostic tests, better preoperative
6 and before they develop medullary thyroid cancer. More localization studies, and new surgical instrumentation, as
information is also available regarding genotype-phenotype well as a better understanding of the natural history of many
relationships in predicting tumor behavior. Familial non- of these disorders.
medullary thyroid cancer with or without other syndromes
has recently become a recognized clinical syndrome, and Orlo H. Clark, MD
the thyroid cancers in these patients are somewhat more
Quan- Yang Duh, MD
aggressive than are sporadic thyroid cancers. Papillary thy-
roid cancer in children and after radiation are frequently Electron Kebebew, MD

xv
 Table of Contents
1 Thyroid physiology 3
Surgical anatomy and embryology of the thyroid and parathyroid
2 9
glands and recurrent and external laryngeal nerves
3 Medical and surgical treatment of endemic goiter 16
4 Sporadic nontoxic goiter 24
5 Thyroiditis 34
6 Hypothyroidism 44
7 Graves' and Plummer's diseases : medical and surgical management 54
Use and abuse of thyroid-stimulating hormone suppressive therapy in
8 patients with nodular goiter and benign or malignant thyroid 68
neoplasms
9 Approach to thyroid nodules 85
10 Childhood thyroid carcinoma 93
11 Papillary thyroid carcinoma : rationale for hemithyroidectomy 102
12 Papillary thyroid carcinoma : rationale for total thyroidectomy 110
13 Follicular neoplasms of the thyroid 115
14 Hurthle cell adenoma and carcinoma 123
15 Medullary thyroid carcinoma 129
16 Localization tests in patients with thyroid cancer 142
Papillary and follicular carcinoma : surgical and radioiodine treatment
17 152
of distant metastases
18 Anaplastic carcinoma of the thyroid gland 159
19 Unusual thyroid cancers, lymphoma, and metastases to the thyroid 168
20 Recurrent thyroid cancer 181
21 Thyroidectomy 188
Management of regional lymph nodes in papillary, follicular, and
22 195
medullary thyroid cancer
23 Occurrence and prevention of complications in thyroid surgery 207
24 Thyroid emergencies : thyroid storm and myxedema coma 216
25 Pathology of tumors of the thyroid gland 223
26 Factors that predispose to thyroid neoplasia 240
27 Predictors of thyroid tumor aggressiveness 248
28 Growth factor, thyroid hyperplasia, and neoplasia 256
29 Signal transduction in thyroid neoplasms 265
30 Oncogenes in thyroid tumors 280
31 Thyroid oncogenesis 288
32 Mechanisms and regulation of invasion in thyroid cancer 295
33 Surgical management of recurrent and intrathoracic goiters 304
Surgical management of advanced thyroid cancer invading the
34 318
aerodigestive tract
35 Potentially new therapies in thyroid cancer 334
36 Comparative genomic hybridization in thyroid neoplasms 344
37 Sodium-iodide symporter and radioactive iodine therapy 355
38 Parathyroid embryology, anatomy, and pathology 365
Parathyroid hormone : regulation of secretion and laboratory
39 372
determination
Diagnosis of primary hyperparathyroidism and indications for
40 384
parathyroidectomy
41 Natural history of untreated primary hyperparathyroidism 393
42 Metabolic complications of primary hyperparathyroidism 402
43 Natural history of treated primary hyperparathyroidism 413
44 Asymptomatic primary hyperparathyroidism 419
45 Normocalcemic hyperparathyroidism 424
46 Localization studies in persistent or recurrent hyperparathyroidism 430
47 Technique of parathyroidectomy 439
Surgical approach to primary hyperparathyroidism (bilateral
48 449
approach)
Surgical approach to primary hyperparathyroidism (unilateral
49 456
approach)
50 Minimally invasive parathyroid surgery 462
51 Endoscopic parathyroidectomy 467
Intraoperative parathyroid hormone assay as a surgical adjunct in
52 472
patients with sporadic primary hyperparathyroidism
53 Parathyroid hyperplasia : parathyroidectomy 481
Familial hyperparathyroidism in multiple endocrine neoplasia
54 489
syndromes
55 Familial hyperparathyroidism 493
56 Metabolic complications of secondary hyperparathyroidism 502
57 Surgical approach to secondary hyperparathyroidism 510
58 Parathyroid reoperations 518
59 Hypoparathyroidism and pseudohypoparathyroidism 527
60 Cryopreservation of parathyroid tissue 530
Hypercalcemia of malignancy and parathyroid hormone-related
61 536
protein
62 Hypercalcemic crisis 543
63 Parathyroid carcinoma 549
64 Surgical embryology and anatomy of the adrenal glands 557
65 Adrenal physiology 571
66 Adrenal imaging procedures 576
67 Clinically inapparent adrenal mass (incidentaloma or adrenaloma) 586
68 Hyperaldosteronism 595
69 Adrenocortical carcinoma : nonfunctioning and functioning 604
70 Cushing's syndrome 612
71 Pheochromocytoma 621
72 Addison's disease and acute adrenal hemorrhage 634
73 Open operative approaches to the adrenal gland 641
74 Laparoscopic adrenalectomy 647
75 Anatomy and embryology of the pancreas 665
76 Multiple endocrine neoplasia type 1 673
77 Transplantation of endocrine cells and tissues 691
78 Pancreatic endocrine physiology 701
79 Insulinomas 715
80 Localization of endocrine pancreatic tumors 730
81 Pancreatic surgery for endocrine tumors 737
82 Gastrinoma 745
83 Multiple endocrine neoplasia type 2B 757
84 Somatostatinoma and rare pancreatic endocrine tumors 764
85 Non-multiple endocrine neoplasia endocrine syndromes 773
86 Neuroendocrine tumors 780
87 Endocrine emergencies : hypoglycemic and hyperglycemic crises 789
88 Chemotherapy for unresectable endocrine neoplasms 800
 Thyroid Physiology
Roderick Clifton-Bligh, MB, BS, PhD • Leigh Delbridge, MD, FRCS

The thyroid gland contains two separate physiologic within the promoters of thyroid-specific genes (e.g., thy-
endocrine systems: one responsible for the production of the roperoxidase and thyroglobulin). Mutation of any of these
thyroid hormones thyroxine (T4 ) and triiodothyronine (T3) , transcription factors leads to thyroid dysgenesis, together
and the other responsible for the production of the hormone with other phenotypic features specific to each transcription
calcitonin. factor (TTF-l, pulmonary disease; Pax-8, renal hemiagenesis;
The functional unit for thyroid hormone production is TTF-2, cleft palate).7-9
the thyroid follicle. This is composed of a single layer of The transcription factor GATA3 has been shown to be
cuboidal follicular cells surrounding a central space filled important in parathyroid gland development since mutations
with colloid. The average size of a follicle varies from 100 in this gene are associated with HDR syndrome (hypoparathy-
to 300 urn, each of which is surrounded by a network of roidism, sensorineural deafness, and renal aplasia).'? Failure
capillaries. The primary function of the thyroid follicle is of parathyroid gland development is also a feature of
to make and store thyroid hormones. DiGeorge syndrome, in which parathyroid and thymic apla-
Calcitonin is produced by C cells within the thyroid. sia are variably accompanied by cardiac defects and facial
These cells, of neural crest origin, lie in a parafollicular posi- malformations owing to microdeletion or rearrangement of
tion in direct contact with the follicular basement membrane. the short arm of chromosome 22. 11 Several transcription
factors involved in the development of the parathyroid
glands in mouse models have been identified," including
Thyroid Embryogenesis Gcm2 and Hoxa3.

Thyroid primordial cells develop from pharyngeal ectoderm,

forming a visible medial anlage by human gestational days
16 to 17.1 The thyroid diverticulum then migrates caudally to
Thyroid Hormone Physiology
reach its final position in the thyroid primordial body anterior
Iodide Metabolism and Uptake
to the cricoid cartilage (Fig. 1-1). Subsequently, these cells
begin to express markers of mature thyrocyte differentiation, Iodine usually enters the body as the result of dietary and water
including proteins that are intrinsic to thyroid secretory uptake, but it can also be found in various drugs, such as cough
function (thyroglobulin, thyroperoxidase, and the sodium- medicines, and in diagnostic agents. Dietary iodine intake
iodide symporter [NIS]), and the thyroid-stimulating hor- varies widely throughout various parts of the world. The rela-
mone (TSH) receptor that controls both thyroid growth and tionship between iodine intake and thyroid disease was first
secretory function. The foramen caecum, at the junction demonstrated by Chatin in 1852, but the practice of iodine sup-
between the anterior two thirds and posterior third of the plementation of food and water, which he recommended, fell
tongue base, remains as an embryologic reminder of thyroid into disrepute and was not revived until the large-scale exper-
origin. Thyrocytes form thyroid follicles, while intervening iments of Marine and Kimball in Ohio in 1917.14 Even in areas
cells derived from the ultimobranchial body within the where endemic goiter is not a problem, iodine intake and
fourth pharyngeal pouch develop into calcitonin-secreting C excretion vary considerably with urinary excretion, ranging
cells (see Fig. 1-1). The parathyroid glands develop from the from as little as 40 ug/day up to 400 ug/day." Iodine defi-
third and fourth pharyngeal pouches and migrate to the pos- ciency is associated with nodular goiter, hypothyroidism,
terior surface of the thyroid gland. The thyroid gland begins and cretinism" as well as the development of follicular
to trap iodide between gestational weeks 10 and 12.1 thyroid carcinoma.!? In areas of the world where iodine
Several transcription factors involved in the development deficiency is still a problem, a variety of measures are being
of the thyroid gland have been identified. Three such fac- introduced to increase iodine intake, such as iodination of
tors-thyroid transcription factors (TTFs)-1 2•3 and _24 and salt, bread, and water to treat entire population groups and
the paired homeodomain factor Pax-85.6-were identified injections of iodized oil for target groups such as pregnant
and isolated by their binding to specific regulatory elements women.P Iodine excess, on the other hand, is associated
3
4 - - Thyroid Gland

FIGURE 1-1. Thyroid embryogenesis. Left, Coronal section through the pharyngeal arch region in a late-somite embryo. The thyroid
diverticulum forms from a thickening in the midline of the anterior pharyngeal floor. The two lateral anlagen (ultimobranchialbodies) are
derived from the fourth or fifth pharyngeal pouch; the thymus and inferior parathyroids are derived from the third pouch, whereas the
superior parathyroid glands form from the fourth pharyngeal pouch (not shown). Right, Ventral view of the pharyngeal organ derivatives
following migration toward their ultimate positions.The thyroid diverticulumhas caudally migrated anterior to the cricoid cartilage, where
it is infiltrated by cells from the ultimobranchial bodies that will form parafollicular C cells. The superior and inferior parathyroid glands
are positioned on the posterolateral surface of the thyroid gland. The two thymic primordia will fuse to become a single gland anterior
to the trachea. (Adapted from Manley NR, Capecchi MR. The role of Hoxa-3 in mouse thymus and thyroid development. Development
1995;12l:l989.)

with an increased incidence of autoimmune thyroid disease

such as Graves' disease and Hashimoto's thyroiditis'S" as
well as papillary thyroid carcinoma. I?
Iodine, in the form of inorganic iodide, is rapidly and
efficiently absorbed from the gastrointestinal tract and
enters the extracellular iodide pool, where it is joined by
iodide derived from the breakdown of previously formed
thyroid hormone. Less than 10% of total body iodide is con-
tained in the extracellular pool; the remaining 90% is stored
in the thyroid gland as either preformed thyroid hormone or
iodinated amino acids.'?
Iodide is taken up from the extracellular space into the
follicular cells by an active transport process. The major
source of loss of iodide from the extracellular space, in addi-
tion to uptake by the thyroid gland, is renal excretion. Small
quantities of iodide are also lost through the skin, through
the saliva, or in expired air. The active transport of iodide
into the cells results in a significant intrathyroidal iodide
gradient. The NIS is part of a family of membrane-associated
transport glycoproteins that probably contain 12 membrane-
spanning domains. 2o•21 Iodide is actively transported using
energy from the coupled inward sodium transport.
Mutations in the NIS gene are associated with goitrous con-
genital hypothyroidism.P Iodide transport into the follicular
cells is influenced by TSH levels as well as by the glandular
content of iodide.

Synthesis of Thyroid Hormone

After uptake into the follicular cells through the basal
membrane (Fig. 1-2), inorganic iodide is rapidly oxidized. FIGURE 1-2. Uptake of iodide into the follicular cell by active
Thyroid hormones are then synthesized by the combination transport, with subsequent iodide oxidation, tyrosine iodination,
of iodine with tyrosyl residues within the protein thyroglob- and iodotyrosine coupling occurring at the apical membrane,
ulin. This reaction is catalyzed by thyroperoxidase in two catalyzed by thyroid peroxidase. DIT = diiodotyrosine; MIT =
principal steps. In the first reaction, iodide reacts with monoiodotyrosine; T3 = triiodothyronine; T4 = thyroxine.
 Thyroid Physiology - - 5

tyrosyl residues in thyroglobulin to form monoiodotyrosine of the thyroid cell, and multiple vesicles containing thy-
(MIT) and diiodotyrosine (DIT). In the second reaction, roglobulin are incorporated into the follicular cell by endocy-
MIT and DIT condense to form 3,5,3'-triiodothyronine (T 3) tosis. Lysosomal hydrolysis of the thyroglobulin, with
or the inactive 3,3',5'-triiodothyronine (rT3) , whereas two reduction of disulfide bonds, leads to release of both T3 and
molecules of DIT condense to form T 4 • T 3 and rT 3 are also T 4 through the basement membrane into the circulation. The
formed by intrathyroidal deiodination of thyroxine, catalyzed ratio of the levels of these two hormones released into the
by deiodinase enzymes.P In conditions of iodine-sufficient peripheral blood approximates their levels in stored thyroglob-
intake, the predominant iodothyronine synthesized by the ulin (T3:T4 is "" 1:13). Very little thyroglobulin reaches the
thyroid gland is T 4 •24 Once formed, the thyroid hormones, peripheral circulation; however, when sensitive immunoassay
covalently bound to thyroglobulin, are stored in colloid procedures are used, small quantities can be detected in normal
within the center of the follicle. The thyroid gland contains a individuals.P Iodotyrosines released from thyroglobulin
very large store of thyroid hormone, which lasts for several undergo deiodination and are recycled, with the iodide so
weeks in the absence of the formation of new hormone. 19 released available for new thyroid hormone synthesis.
Thyroid peroxidase (TPO) is a membrane-bound glyco-
protein that is localized to the apical membrane of the follic- Peripheral Transport and Metabolism of
ular cell; the peroxidase reactions occur at the cell-colloid Thyroid Hormones
interface.f TPO has now been cloned and has been shown to
have a hydrophobic signal peptide at its aminoterminus and a More than 99% of circulating thyroid hormones are bound
hydrophobic region with the characteristics of a transmem- to serum proteins, including thyroxine-binding globulin
brane domain near the carboxylterminus.P This structure is (TBG), transthyretin, and albumin." TBG is a glycoprotein
consistent with TPO being a membrane-associated protein. that contains only one binding site per molecule. TBG is
The synthesis of thyroglobulin occurs exclusively in the thy- responsible for the transport of more than three fourths of
roid gland, where homodimers are formed in the endoplasmic thyroid hormone in the blood, and its levels are significantly
reticulum before being transported into the apical lumen of increased by elevated levels of estrogens, as occurs in preg-
thyroid follicles.P Defects in thyroglobulin synthesis usually nancy. Dissociation of the free hormone from its binding
cause moderate to severe hypothyroidism in association proteins is rapid and efficient. Thyroid hormones are
with low circulating thyroglobulin levels." A partial organ- lipophilic and are capable of passive diffusion into cells,
ification defect and goiter (with or without overt hypothy- although specific transporters may also regulate intracellular
roidism) is associated with sensorineural deafness in thyroid hormone content."
Pendred's syndrome. Mutations in a putative sulfate trans- T 3 synthesized directly by the thyroid forms a relatively
porter gene (PDS) have recently been associated with this small proportion of the effective T 3 concentration in tissues,
disorder," Although the precise mechanisms by which which is mainly derived from peripheral deiodination of T4 .
the pendrin protein causes the phenotype is unclear, it is pro- This reaction is catalyzed by two deiodinases with charac-
posed that defective sulfation of thyroglobulin impairs its teristic tissue distributions. Type I deiodinase (5'DI) is pre-
subsequent iodination." dominant in liver, kidney, and thyroid, whereas type II
Release of thyroid hormone into the peripheral blood deiodinase (5'DII) is present in the central nervous system,
occurs as the result of lysosomal hydrolysis within the follicu- pituitary, placenta, brown adipose tissue, cardiac and skele-
lar cells (Fig. 1-3). Pseudopodia form at the apical membrane tal muscle, and thyroid.'? A third deiodinase (5'DIII) cat-
alyzes deiodination of T 4 to rT 3 or T 3 to diiodothyronine (T 2)
and is found in the placenta and central nervous system."
These differences in distribution and regulation may explain
some tissue-specific variation in thyroid hormone action.
Peripheral conversion of T 4 to T 3 may be impaired in a
number of situations, including systemic illness, malnutri-
tion, and trauma or by various drugs.
The thyroid hormones generally have slow turnover
times in the peripheral circulation. In adults, the half-life of
T 4 is about 7 days, presumably because of the high degree
of binding of T4 to its carrier proteins, whereas the half-life
of T, is approximately 8 to 12 hours.

Peripheral Action of Thyroid Hormones

The major effects of thyroid hormone action occur through
the intranuclear action of Tj, with T4 being largely a prohor-
mone." It remains controversial as to whether T 4 might also
regulate non-nuclear biologic responses in some contexts,
for instance, the activation of certain mitochondrial or cell-
FIGURE 1-3. Lysosomal hydrolysis of pinocytotic vesicles containing membrane enzymes." In the 1960s, Tata and associates
stored colloid, with subsequent release of thyroid hormone into the observed that T3 treatment resulted in the rapid synthesis of
peripheral circulation. T 3 = triiodothyronine; T4 = thyroxine. nuclear RNA, which preceded increases in protein synthesis
6 - - Thyroid Gland

and mitochondrial oxygen consumption." Subsequently, sub- The clinical manifestations of thyroid hormone action
cellular fractionation demonstrated specific nuclear binding are the net result of the actions of the products of the vari-
sites for T 3 and identified the anterior pituitary, liver, brain, ous genes whose expression is regulated by T 3. For example,
and heart as having high binding capacity for T 3.3! Thus, the thyroid hormones affect cardiac contractility by affecting
current concept of thyroid hormone action is that its nuclear the transcription of, and subsequent relative proportions of,
receptor binds to specific regulatory regions in target genes the various myosin heavy chains in cardiac muscle.P'" In the
and regulates gene transcription in response to T 3.32-34 pituitary, T 3 regulates the transcription of the genes for both
Thyroid hormone receptors (TRs) are members of the ex and ~ subunits of TSH, thus affecting the level of TSH
steroid hormone receptor superfamily. There are two TR secretion.'?
genes, a and ~, located on chromosomes 17 and 3, respec-
tively, and differential splicing of both these genes yields Thyroid Hormone Regulation
a total of four isoforms, denoted as TRal, TRa2, TRf3I, and
TRf32 (Fig. 1_4).32 The expression of the various TR iso- Thyroid hormone production and release are under the con-
forms is both developmentally regulated and tissue specific, trol of the hypothalamic-pituitary-thyroid axis (Fig. 1-5),
such that TRa is widely expressed at all stages of develop- acting in a negative-feedback cycle. TSH is the major regu-
ment, preceding the appearance of endogenous thyroid hor- lator of thyroid gland activity. Increased levels of TSH lead
mone, whereas TR~ begins to be expressed as thyroid to hypertrophy and increased vascularity of the gland,
hormone-dependent processes occur," An aminoterminal whereas decreased levels of TSH lead to gland atrophy.
splice variant of the TR~ receptor, TR~2 is specifically A glycoprotein secreted by the anterior pituitary, TSH is
expressed in the hypothalamus and pituitary and may there- composed of an a subunit and a ~ subunit. The ex subunit is
fore be the critical subtype involved in negative-feedback common to a family of glycoprotein hormones, including
effects of T 3.32 In the adult, TRal may be the predominant
isoform in myocardium, skeletal muscle, and fat, whereas
TR~l and TR~2 predominate in the pituitary and liver."
TRa2 does not bind ligand and its function is poorly under-
stood, although it may function as an inhibitor of thyroid
hormone action in some contexts.F
TRs bind to specific regulatory DNA sequences usually
within gene promoters.P A consensus regulatory binding
site, termed the thyroid hormone response element (TRE),
consists of a pair of hexanucleotide half-sites. Natural TREs
present in gene promoters are commonly degenerate varia-
tions of these consensus sequences. Biochemical evidence
suggests that on many TREs, the receptor complex is most
active when bound to DNA as a heterodimer with the
retinoid X receptor."

FIGURE 1-4. Multiple human thyroid hormone receptor (TR) iso-

forms, TRa and TR~ receptors are transcribed from different genes
on chromosomes 17 and 3, respectively. Different isofonns are
then generated from differential splicing of the primary messenger
RNA transcripts in each case, such that TRal and TRa2 isofonns
differ in their carboxytennini, whereas TR~I and TR~2 isofonns
differ in their aminotermini, as shown. (Adapted from Lazar MA. FIGURE 1-5. Negative-feedback regulation of thyroid hormone
Thyroid hormone receptors: Multiple forms, multiple possibilities. production. TRH = thyrotropin-releasing hormone; TSH = thyroid-
Endocr Rev 1993;14:184.) stimulating hormone; T 3 = triiodothyronine; T 4 = thyroxine.
 Thyroid Physiology - - 7

follicle-stimulating hormone, luteinizing hormone, and iodide availability. For example, an excess of dietary iodide
human chorionic gonadotropin (hCG). leads to autoregulated inhibition of iodide uptake into the fol-
TSH binds to a specific receptor on the surface of the thy- licular cells, whereas iodide deficiency results in increased
roid cell. The TSH receptor is a G protein-coupled receptor. iodide transport and uptake. Large doses of iodide have more
After activation by TSH, the receptor interacts with a gua- complex effects, including an initial increase followed by a
nine nucleotide-binding protein (G protein), which induces decrease in organification, the so-called Wolff-Chaikoff
the production of cyclic adenosine monophosphate (cAMP).4o effect." Excess iodide also inhibits, at least initially, the
This cAMP then stimulates the synthesis and secretion of release of stored thyroid hormone from the thyroid follicle.
thyroid hormones. Receptors that are linked to G proteins
are characterized by the presence of seven transmembrane-
spanning domains linked by cytoplasmic and extracellular Calcitonin Physiology
loops. The first cytoplasmic loop, as well as the carboxylterrni-
nal residues in the second and third cytoplasmic loops, are Calcitonin Secretion
important in mediating a TSH-dependent increase in intracel-
lular cAMP production." The TSH receptor has been cloned.f Calcitonin is secreted by the parafollicular C cells located in
and specific mutations have been identified in association with the lateral lobes of the thyroid. This hormone is a 32-amino
hyperfunctioning follicular thyroid neoplasms.tv" acid polypeptide with an NH-terminal 7-member disulfide
TSH is secreted from the anterior pituitary in response ring."? Calcitonin acts to lower serum calcium concentra-
to thyrotropin-releasing hormone (TRH) and to reduced tion, principally by inhibition of bone resorption. Secretion
pituitary levels of T; TRH acts to directly stimulate the thy- of the hormone is increased in the presence of elevated levels
rotropic cells to increase both the synthesis and the release of of serum calcium. In the clinical context, calcitonin secretion
TSH. TRH is a tripeptide synthesized in the paraventricular can be stimulated by a number of techniques, including cal-
nucleus of the hypothalamus, and, after synthesis, it passes cium infusion, pentagastrin infusion, and alcohol.t''
to the median eminence and down the pituitary stalk in the
hypophysial portal system. It is thought that the principal Peripheral Action of Calcitonin
function of TRH is to set the ambient level of regulatory con-
trol whereby thyroid hormone levels are mediated by negative Calcitonin acts via specific cell surface receptors located
feedback. TRH secretion itself is also under negative-feedback predominantly on the surface of osteoclasts." These recep-
control in response to peripheral thyroid hormone levels. tors have also been found in renal tubular epithelium, neural
T 3, on the other hand, derived principally from the local tissue, and lymphocytes.t" The predominant action of calci-
deiodination of peripheral T 4 in the pituitary, directly tonin is to inhibit osteoclast action, although in the physio-
inhibits the release and synthesis of TSH. It is also thought logic situation calcitonin does not actually cause a lowering
that peripheral thyroid hormone levels may regulate TRH of s~rum calcium levels. Indeed, in patients with medullary
receptor numbers on the surface of the pituitary thyrotropic carcinoma of the thyroid, in which calcitonin levels may be
cells, thus decreasing their responsiveness to TRH. many thousands of times the normal level, hypocalcemia is
A number of other factors affect thyroid hormone synthe- not seen. Similarly, patients who have had a total thyroidec-
sis in addition to the hypothalamic-pituitary feedback cycle. tomy, with removal of all known C cells, maintain normal
Other hormones can have a direct effect on the thyroid calcium metabolism.
gland. Catecholamines are thought to have a direct stimula-
tory effect on thyroid hormone release. hCG also stimulates
thyroid hormone production, with free levels of thyroid Summary
hormone increasing during pregnancy and in the presence of
hydatidiform moles." Glucocorticoids, on the other hand, In summary, the thyroid gland contains two separate func-
act to reduce thyroid hormone production by suppressing tioning units. The follicular cells produce T 4 and T 3, which
pituitary TSH secretion. The thyroid also obtains direct regulate growth and metabolism, whereas the parafollicular
adrenergic innervation, and there is some evidence that sym- cells produce the antihypercalcemia hormone calcitonin.
pathetic stimulation can increase thyroid hormone synthesis. Iodine is required for the synthesis of thyroid hormone, and
Other external factors that can affect thyroid regulation iodine deficiency can result in endemic goiter and cretinism.
include nonthyroidal illness, starvation, and temperature Circulating levels of thyroid hormone depend on a negative
changes. A variety of disorders, especially severe illness, feedback between T 3 and T 4 and TSH secretion as well as a
lead to reduced levels of peripheral thyroid hormone in the positive action of TSH. Thus, medications and other factors
absence of a compensatory rise in TSH (the so-called sick can influence ambient thyroid hormone levels and, conse-
euthyroid syndrome). Starvation also leads to markedly quently, the metabolic state.
reduced levels of both T 4 and T 3 , as does exposure to high
temperatures.
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8 -- Thyroid Gland

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9. Clifton-Bligh RJ, Wentworth JM, Heinz P, et al. Mutation of the gene 35. Glass CK. Differential recognition of target genes by nuclear receptor
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causes human HDR syndrome. Nature 2000;406:419. receptors to their cognate response elements. Cell 1991;67:1251.
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12. Gunther T, Chen Z-F, Kim J, et al. Genetic ablation of parathyroid 38. Morkin E. Regulation of myosin heavy chain genes in the heart.
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13. Manley NR, Capecchi MR. The role of Hoxa-3 in mouse thymus and thyrotropin gene expression. Rec Prog Horm Res 1993;48:393.
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15. Laurence P. Iodine intake: What are we aiming at? [Editorial] J Clin 41. Chazenbalk GD, Nagayama Y, Russo D, et al. Functional analysis of
Endocrinol Metab 1994;79: 17. the cytoplasmic domains of the human thyrotropin receptor by site
16. Boyages Sc. Iodine deficiency disorders. J Clin Endocrinol Metab directed mutagenesis. J Bioi Chern 1990;265:20970.
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Saunders, 1992, p 357. Metab 1994;79:657.
20. Dai G, Levy 0, Carrasco N. Cloning and characterization of the thy- 45. Yoshikawa N, Nishikawa N, Horimoto M, et al. Thyroid-stimulating
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1997;17:411.
 Surgical Anatomy and
Embryology of the Thyroid
and Parathyroid Glands
and Recurrent and External
Laryngeal Nerves
Jean-Francois Henry, MD

The surgical anatomy of the thyroid, parathyroid glands, and The normal adult thyroid gland is composed of two lat-
recurrent and external laryngeal nerves should be consid- eral lobes connected by an isthmus. Anomalies of embry-
ered as a whole. A thorough knowledge of the anatomy and onic development of the two lobes result in a large variety
an understanding of the embryonic development of the of shapes and sizes. Rarely, in fewer than 0.1 % of cases, the
thyroid and parathyroid glands are the keys to successful isthmus or one lobe may not develop.
surgery. The thyroglossal duct may persist or may differentiate
into thyroid tissue at any level. Normally, the epithelium of
the thyroglossal duct disappears. Occasionally, the epithe-
Thyroid Embryology and lium and the duct may form thyroglossal cysts or fistulas,
Developmental Abnormalities which usually present above the hyoid bone but may occur
at any site along the duct between the base of the tongue and
The thyroid gland has a double origin from the primitive the suprasternal notch. These are essentially midline struc-
pharynx and the neural crest. The main body of the thyroid tures. Because the duct passes through or anterior or poster-
gland is derived from epithelial cells of the endoderm of the ior to the hyoid bone, excision of the midsection of the
primitive pharynx. These cells will form the greater portion hyoid bone is necessary for complete excision of the entire
of the follicular elements of the thyroid tissue. They arise cyst and thyroglossal duct up to the foramen cecum.
as a diverticulum from the midline of the pharyngeal floor. Midline ectopic thyroid rests are the result of the failure
It soon develops as a bilobed, encapsulated structure that of or incomplete descent of the thyroglossal duct and of
descends in the midline of the neck. With further develop- abnormal development of its epithelium. The most common
ment, this diverticulum remains attached to the buccal cavity example is the pyramidal lobe, which extends upward from
by a narrow tract-the thyroglossal duct. Its distal end may the isthmus or from either lateral lobe in about 30% of
become the pyramidal lobe. patients. It may be considerably enlarged in patients with
The neural crest is the source of the parafollicular cells, endemic goiters and in Graves' disease. In the latter case,
or C cells, which secrete calcitonin. 1,2 These C cells migrate if overlooked, it may be responsible for recurrent hyperthy-
from the neural crest of the ultimobranchial bodies of the roidism. Complete failure of descent of the thyroglossal
fourth branchial pouch (P IV) and the fifth branchial pouch. duct results in a lingual thyroid, located at the base of the
The incorporation of the fifth pouch with the P IV leads tongue. A lingual thyroid may be the only functioning
to the formation of the caudal-pharyngeal complex, which tissue and may be responsible for lingual goiter; symptoms
includes not only the ultimobranchial bodies (lateral thy- depend on its size. Other midline ectopic thyroid rests
roids) but also the parathyroid glands arising from the endo- of the thyroglossal duct may be found below or above
derm of the P IV. Eventually, C cells populate the thyroid the hyoid bone. Usually asymptomatic, they are demon-
tissue by way of its lateral lobes, which join the main body strated on radioiodine scanning after total thyroidectomy.
on each side (Fig. 2-1). Carcinomas may rarely arise in median ectopic thyroid tissue.
9
10 - - Thyroid Gland

it as the origin of the thymus IV (rudimentary thymus IV),

which rapidly undergoes involution. The fatty lobules some-
times found at the site of the upper parathyroid (P IV) may
well constitute the vestigial remnants of this thymus IV.
At the 13- to 14-mm stage, the P III and P IV migrate
together with the thymus and ultimobranchial bodies,
respectively. The P III-thymus complex separates from the
pharyngeal wall and moves toward the caudal and medial
regions. Because of the extension of the cervical spine and
the descent of the heart and great vessels, the thymus and
the P III are drawn toward the superior mediastinum. At the
20-mm stage, the cephalic regression of the thymus brings
about its separation from the P III, which are thus aban-
doned at the level of the anterior or posterolateral region
FIGURE 2-1. Schematic view of embryonic migrations of parafol- of the inferior poles of the thyroid lobes or at the level of
Iicular andparathyroid tissues. At the 13- to l4-mm stage, the P III thyrothymic ligaments, vestigial structures indicative of
and P IV migrate together with the thymus and ultimobranchial their former connections. This embryologic migration
bodies, respectively. results in an extensive area of dispersal of the normal P III.
In 61% of cases, they are situated at the level of the inferior
poles of the thyroid lobes on the posterior, lateral, or ante-
About I % of thyroglossal cysts contain papillary thyroid rior aspects. In 26% of cases, they are situated in the thy-
cancers. rothymic ligaments or on the upper cervical portion of the
Aberrant thyroid tissue has also been identified lateral or thymus. More rarely, in 7% of cases, they are situated higher
inferior to the main body of the thyroid gland and in the up, at the level of the middle third of the posterior aspect
superior anterior mediastinum. When aberrant thyroid tissue of the thyroid lobes, and may then be confused with P IV
is situated lateral to the jugular vein and is unassociated with (Fig. 2-2).
lymph node tissue, it may rarely be a developmental anom- The P IV follow the thyroid migration of the ultimo-
aly deriving from the fourth pouch. Ectopic intrathoracic branchial bodies, which travel toward the lateral part of the
thyroid tissue may also be found in the periaortic region main median thyroid rudiment. Their descent in the neck is
and the pericardium. It is the result of the displacement of thus relatively limited. They remain in contact with the pos-
thyroid rests into the mediastinum by the descent of the terior part of the middle third of the thyroid lobes. The short
heart and great vessels. Because their blood supply is from course of embryonic migration of P IV explains why they
intrathoracic vessels, tumors arising from these thyroid remain relatively stable in their topography when they are
remnants usually cannot be removed by cervicotomy and not pathologic. Thus, in 85% of cases, they are grouped at
require a sternum-splitting incision. the posterior aspect of the thyroid lobes, in an area 2 em in
In contrast with the former rare situations, what appears diameter, whose center is situated about 1 em above the
on histologic examination to be normal thyroid tissue within
lymph nodes lateral to the jugular vein in fact represents
metastatic papillary thyroid carcinoma. On the other hand,
on rare occasions, a few follicles of normal thyroid tissue are
observed within the capsule of medially located lymph nodes.
They do not necessarily represent metastases, provided that
the follicular cells appear normal and the follicles are limited
to the periphery of the lymph node. It has been demonstrated
that in these rare cases, the thyroid gland is entirely normal
at meticulous histologic examination.' Thyroid tissue may
also rarely be found in ovarian teratomas. In rare instances,
when thyroid tissue is the main component, struma ovarii
may arise and be responsible for thyrotoxicosis or malignancy
with peritoneal metastases.

Parathyroid Embryology and

Developmental Abnormalities
The inferior parathyroid glands arise from the dorsal part of
the P III. The thymus arises from the ventral portion of the
same pouch. This common origin justifies labeling P III and
thymus as parathymus. The dorsal part of the P IV gives rise FIGURE 2-2. The embryonic migration of the third branchial
to the superior parathyroids. The fate of the ventral portion of pouch (P III)-thymus complex results in an extensive area of the
the P IV is little understood in humans. Gilmour" regarded normal P III from the angleof the mandible to pericardium.
 Surgical Anatomy and Embryology of the Thyroid and Parathyroid Glands - - 11

arising from fragmentation of the pharyngotracheal duct

when the pharyngeal pouches separate from the pharynx.
The incidence of these supernumerary glands is relatively
high at 13%.5 Akerstrom and colleagues' distinguish
between accessory parathyroid glands containing simple
tissue debris and weighing less than 5 mg, found very close
to the main glands, and true supernumerary glands weighing
more than 5 mg (average weight, 24 mg) situated apart from
the other glands.
FIGURE 2-3. The short course of embryonic migration of the Ectopic or supernumerary parathyroids may also be situ-
fourth branchial pouches explains why they remain relatively ated in quite exceptional positions. They are then revealed
stable in the topography when they are not pathologic. In 85% of by tumoral formations developing from them and are
cases, they are grouped at the junction of the middle and superior responsible for hyperparathyroidism: in the middle medi-
thirds of the posterior aspect of the thyroid lobe.
astinum (0.3%) at the level of the aortopulmonary window,"
lateral to the jugulocarotid axis." The migration of patho-
logic parathyroid tissue seems highly improbable in such
crossing of the inferior thyroid artery and the recurrent nerve cases. In both cases, the embryologic hypotheses suggest a
(Fig. 2_3).4.6 Thus, the P IV are crossed by the P III during precocious fragmentation of P Iy' 15.16
the descent of the parathymus. This embryonic crossing of Parathyroid tissue'? and parathyroid adenomas" have
P III and P IV explains why their grouping at the level of also been described within the vagus nerve. In the latter
the inferior thyroid artery, at the junction of the middle and case, it has been hypothesized that parathyroid tissue arises
inferior thirds of the thyroid lobe, is more or less close, from the P III, which is closely related to the vagus nerve
depending on the migration of P III. during embryogenesis.'? A case of a parathyroid located in
Because the area of dispersal of the P IV is limited by the mucosa of the piriform sinus has even been reported. 19
their short migratory course, a congenital ectopic position of
P IV is unusual. In 12% to 13% of cases, the glands are on
the posterior aspect of the superior pole of the thyroid lobe Surgical Anatomy of the
in a laterocricoid, lateropharyngeal, or intercricothyroid Thyroid and Parathyroid Glands
position, and, exceptionally, in less than 1% of cases, they
are above the upper pole of the lobe. In 1% to 4% of cases, The normal adult thyroid gland weighs about 17 g. It is
they are frankly posterior behind the pharynx or esophagus. wrapped around the anterolateral portion of the upper tra-
Because the embryonic descent of the thymus extends cheal rings and larynx. Each lobe occupies a bed between
from the angle of the mandible to the pericardium, anom- the trachea and the esophagus medially; the carotid sheath
alies of migration of the parathymus, whether excessive or posteriorly; and the sternocleidomastoid, the sternohyoid,
defective, are responsible for high or low ectopias of P III. and the sternothyroid muscles laterally and anteriorly. If the
The incidence of high ectopias, along the carotid sheath, sternothyroid and sternohyoid muscles are to be divided
from the angle of the mandible to the lower pole of the thy- transversely, they must be transected high, at the cricoid
roid, does not seem to exceed 1% to 2%.5.8 Conversely, if level, to preserve their motor nerve, the ansa hypoglossi.
their separation from the thymus is delayed, the P III may be Section of the strap muscles has no clinical functional
dragged down into the anterior mediastinum to a varying consequence.
degree. They are then usually in the thymus, at the posterior The normal thyroid is soft, dark wine-red in color, and
aspect of its capsule, or still in contact with the great medi- covered with a thin capsule. It is loosely attached to neigh-
astinal vessels. These low ectopias are found in 3.9% to 5% boring structures. The variations in fixation of the gland may
of cases.v" Parathyroid glands found in the posterosuperior arouse suspicion of pathologic change, particularly when
mediastinum are usually tumoral P IV that have migrated the history suggests acute thyroiditis or cancer. Normally,
subsequently because of gravity." the gland adheres only to the cricoid cartilage and the upper
The strictly intrathyroid localization of some parathy- tracheal rings. This is the posterior suspensory, or Berry's,
roids is explicable only on embryologic grounds. According ligament.
to Wang,1O the P IV may become included within the thyroid The superior and inferior thyroid arteries are derived
at the time of fusion of the ultimobranchial bodies with the from the external carotid arteries and the thyrocervical
median thyroid rudiment. Although the P III do not arise trunks, respectively. Occasionally, a branch from the innom-
from the P IV, undeniable cases of a normal or pathologic inate artery or aorta, the arteria thyroidea ima, may be pres-
P III included in the lower poles of the thyroid lobes have ent. It passes directly upward in front of the trachea to enter
been reported.t'! According to Gilmour," intrathyroid the lower border of the isthmus. Its frequency of occurrence
inclusion of parathyroid tissue may be found with the same has been greatly overemphasized.
incidence as inclusions of thymic tissue. Overall, the inci- The superior thyroid artery is the first branch of the exter-
dence of intrathyroid ectopias that seem to involve both P III nal carotid artery. It arises just above the thyroid cartilage. It
and P IV is between 0.5% and 3.5%.4,8-11 gives off the superior laryngeal artery and then descends on
Other embryologic cervical or mediastinal ectopic glands the surface of the inferior constrictor of the pharynx, deep to
are more rare and usually related to supernumerary the sternothyroid muscle. It enters the upper pole of the thy-
glands. 13, 14 These develop from accessory parathyroid debris roid on its anterosuperior surface. It gives off a relatively
12 - - Thyroid Gland

level of the cricoid cartilage, loops medially and downward

to a level above the inferior pole of the thyroid, crossing the
sympathetic trunk or its branches, and then runs upward
again to reach the gland at its midportion. For the surgeon,
the inferior thyroid artery appears from beneath the carotid
artery only when the thyroid gland is retracted medially and
the jugular vein laterally. This maneuver puts tension on the
artery and makes it easier to identify. Before entering the thy-
roid, the artery usually divides into three branches: inferior,
posterior, and internal. One branch or sometimes the trunk
itself supplies the inferior parathyroid or P III.
The inferior thyroid artery and its terminal branches are
intimately associated with the recurrent laryngeal nerve at
about the level of the junctions of the lower and middle
FIGURE 2-4. Relation between the external branchof the superior thirds of the thyroid gland (Fig. 2-5). The left recurrent
laryngeal nerve and the thyroid artery. The nerve may run partly to laryngeal nerve ascends at the depth of the tracheo-
or around the artery or its branches. esophageal groove or just lateral to it at the lower pole of the
thyroid. Usually it crosses deep to the inferior thyroid artery,
sometimes between the terminal branches of the artery,
rarely superficially. The right recurrent laryngeal nerve
large branch to the pyramidal lobe and isthmus. The superior courses more obliquely, being somewhat more lateral in
thyroid artery, via its posterior branch, feeds the superior position caudally. It rarely crosses deep to the artery, usually
parathyroid or P IV. There is an extremely close relationship between its terminal branches. Innumerable variations have
between the superior thyroid artery and the external branch been described.F This is one of the most vulnerable areas
of the superior laryngeal nerve (Fig. 2_4).20.2\ This nerve is for injury to the recurrent laryngeal nerve.
the motor nerve to the cricothyroid muscle, which produces From a practical point of view, it is safer to search for the
tension of the vocal cord and makes possible the production nerve below the artery. Identification of the inferior thyroid
of high-pitched voice sounds. Injuries to the nerve, in partic- artery and careful ligation of its branches close to the gland
ular bilateral injuries, are easily overlooked at postoperative is an excellent means of preserving the nerve and the infe-
laryngoscopy. In 6% to 18% of cases, the external branch of rior parathyroid. The recurrent nerve may be mistaken for
the superior laryngeal nerve runs with or around the superior one branch of the artery and especially for the inferior laryn-
thyroid artery or its branches. Therefore, the nerve is highly geal artery. The nerve is somewhat less regular, rounded,
vulnerable during ligation of the superior thyroid artery. and elastic than the artery. A small, red, sinuous vessel, a
Nevertheless, routine identification of the nerve during thy- vasa nervorum, is always observed on it. The tortuousity of
roid surgery is usually not advocated. Indeed, in 20% of this small vessel is reduced when retraction of the thyroid
cases, the nerve is not located in the surgically accessible puts the nerve under tension. Rarely, the nerve branches
area around the superior thyroid pole. It cannot be identified below the inferior thyroid artery. In any case, the surgeon
without dissection into or through the fibers of the pharyn- must consider each extralaryngeal branch of the recurrent
geal constrictor muscle. nerve as the possible motor branch and make every attempt
To avoid nerve injury when ligating the superior thyroid to preserve them all.
vascular pedicle, one may recommend first identifying the
branches of the artery to avoid ligation of its main trunk.
This identification is particularly recommended during exci-
sion of pathologically enlarged thyroid glands. The superior
thyroid arteries should be ligated as low as possible on
the thyroid gland. Second, it is advisable to dissect the supe-
rior thyroid vessels away from the nerve by opening up a
space between the cricothyroid muscle and the upper pole of
the thyroid. This dissection requires strong downward and
outward traction on the upper pole of the gland. During this
traction, the nerve should be sought more or less trans-
versely between the superior thyroid vessels and the pharyn-
geal constrictor muscle or the cricothyroid muscle. Finally,
the dissection must be performed from medial to lateral.
Moreover, small vessels run from the superior thyroid artery
into the pharyngeal constrictor and the cricothyroid mus-
cles. As the nerve slips under these muscles, there is a risk FIGURE 2-5. Recurrent laryngeal nerve and its relationship to the
of heat injury to the nerve during cauterization of these little inferior thyroid arteryandto Berry's ligament. The nerve is embed-
muscular vascular branches. ded in the posterior portion of Berry's ligament. It is accompanied
The inferior thyroid artery arises from the thyrocervical by the inferiorlaryngeal artery, whichgivesoff a small branch that
trunk. It runs upward behind the carotid sheath to about the crosses the nerve internally.
 Surgical Anatomy and Embryology of the Thyroid and Parathyroid Glands - - 13

The recurrent laryngeal nerve continues upward and The nervous branch has only been described running in the
medially at the posterolateral aspect of the middle third of usual pathway of a recurrent laryngeal nerve and having a
the thyroid gland. It is extremely close to the capsule of the small caliber. Whether this branch really originates from the
gland. In a few cases, particularly in pathologically enlarged vagus nerve and not from the sympathetic system, for exam-
glands, it may appear to penetrate or may actually penetrate ple, the stellate ganglion, has not been proved."
the thyroid gland itself before entering the larynx. At the two During thyroid lobectomy, if the nerve is not found at its
upper tracheal rings, the nerve is embedded in the posterior usual place, before it crosses the inferior thyroid artery, it
portion of Berry's ligament (see Fig. 2-5). This ligament should be sought more or less transversely between the lat-
extends posteriorly behind the recurrent nerve and loosely erally retracted carotid sheath and the medially retracted
attaches the thyroid to the esophagus. Vessels and connec- thyroid in a plane that, in the case of nerve anomaly, cannot
tive tissue are more condensed anteriorly at the level of the be cleaved as easily as usual, because the nonrecurrent infe-
tracheal rings. The nerve commonly divides before the point rior laryngeal nerve links the two structures.
at which it enters the larynx, posterior to the cricothyroid Other aberrant pathways for the recurrent laryngeal nerve
muscle. The nerve is accompanied by the inferior laryngeal are observed only with pathologically enlarged thyroids and
artery. At the site of Berry's ligament, this artery, usually particularly with large posterior nodules and in substernal
just posterior to the recurrent nerve, gives off a small branch multinodular goiters. In these cases, if it is not possible to
that crosses the nerve to enter the thyroid glands. Therefore, search for the nerve at its usual place, below the inferior
bleeding vessels in this portion of the ligament should never thyroid artery, it should be located superiorly near to where
be clamped until the nerve has been identified. It is in this it enters the larynx at the level of the cricoid cartilage. This
area that the recurrent nerve is most vulnerable to injury. maneuver requires previous dissection of the upper pole of
Medial retraction on the thyroid lobe makes the nerve more the gland, or an "inside-out" approach, after section of the
vulnerable to injury during lobectomy. Indeed, this maneu- isthmus. Then the nerve should be dissected in a downward
ver puts tension on the inferior thyroid artery and its direction.
branches and on Berry's ligament; consequently, the nerve The venous drainage is more variable than the arterial
is displaced anteriorly on the lateral aspect of the trachea. supply. The capsular veins vary in size and may be enor-
Moreover, the posterior fibers of Berry's ligament press the mous in pathologic glands. These are thin-walled structures
nerve against the lateral aspect of the tracheal rings, increas- that intercommunicate freely among themselves, forming
ing the difficulties of dissection. Instead of medial retrac- a characteristic capsular network. The vessels within the
tion, it is preferable to retract the lobe upward after complete gland itself are relatively small. Consequently, hemorrhage
dissection of its lower pole. With this maneuver, it is easier from capsular vessels may be important, but, provided that
to follow the nerve until its entry in the larynx at the level of the vessels are clamped, subtotal resection of a lobe is a
the cricoid cartilage. relatively bloodless procedure. The capsular network is
The recurrent laryngeal nerve is the motor nerve to the schematically drained by three pedicles. The superior thy-
intrinsic muscles of the larynx." Injury to the motor trunk roid veins, just anterior and lateral to the superior thyroid
causes paralysis of the vocal cord on the ipsilateral side. The artery, empty directly or indirectly into the internal jugular
other extralaryngeal branches are sensory. vein. The lateral or middle veins vary greatly in number.
On rare occasions (0.63%), the right inferior laryngeal They pass directly from the anterolateral border of the lobe
nerve does not recur'" On the left side, this anomaly is quite into the internal jugular vein. Careful lateral retraction of the
exceptional (0.04%). As a rule, the origin of the nonrecur- carotid sheath facilitates their identification and their liga-
rent laryngeal nerve is cervical. Depending on its level of tion, especially in enlarged glands where they may be mis-
origin, the nerve runs more or less down along the vagus taken for capsular veins. The inferior thyroid veins leave the
nerve and more or less across the jugulocarotid groove, lower pole and the isthmus in several trunks, frequently
making a downward curve. It always passes behind the forming a plexus. They empty into the internal jugular vein
common carotid artery. In one third of cases, it is in close and directly into the innominate vein. Ligation of the most
contact with the trunk or the branches of the inferior thyroid lateral inferior thyroid veins requires previous identification
artery; it enters the larynx at the usual level. Nonrecurrence of the recurrent nerve. The nerve may be anterior and, par-
of the inferior laryngeal nerve results from a vascular anom- ticularly when the thyroid lobe is medially retracted, could
aly during embryonic development of the aortic arches: no be mistaken for a vein. Follicular carcinomas, because of
innominate artery, but an aberrant subclavian artery (arteria their high tendency for vascular invasion, may spread
lusoria). Nerve anomaly on the left side requires, in addi- directly through veins into the internal jugular veins and
tion, a right aortic arch associated with situs inversus vis- sometimes downward into the innominate vein. In such
cerum. A nonrecurrent laryngeal nerve has been also cases, previous distal control of these veins is mandatory
reported in association with an ipsilateral recurrent laryn- before thyroidectomy.
geal nerve.25-28 Curiously, in some cases, no vascular anom- Lymphatic drainage of the thyroid is extensive and may
aly has been demonstrated." The supposed coexistence of a flow practically in all directions. Capsular lymph channels,
recurrent and a nonrecurrent laryngeal nerve is questionable. draining the intraglandular capillaries, may even cross-
First, an enlarged anastomotic branch between the cervical communicate with the isthmus and opposite lobe. Therefore,
sympathetic system and the recurrent laryngeal nerve it is technically impossible to remove all the potential lymph
may be mistaken for nonrecurrent laryngeal nerve." node metastases in thyroid cancers.
Second, in the reported cases, it has never been demonstrated Nevertheless, and from a practical point of view, the sur-
that the recurrent branch originated from the vagus nerve. geon must consider two zones of lymphatic drainage for the
14 - - Thyroid Gland

zones of lymphatic drainage. Some of the involvement prob-

ably is brought about by retrograde extension resulting from
obstruction of the lymph flow route in the central neck area."
Because the visceral or central compartment of the neck
is the primary zone of involvement, many surgeons advocate
prophylactic neck dissection in this area in cases of papillary
and medullary thyroid carcinomas. Indeed, even if metasta-
tic nodal recurrences are rare, reoperations in the central
neck area are difficult and increase the risk of injury to the
recurrent laryngeal nerve and parathyroid glands.
Just as embryology helps the surgeon understand where
the parathyroid glands are positioned, their gross appear-
ance makes it possible to identify them and to differentiate
them from other structures. The parathyroid glands vary in
shape but remain compact in 94% to 98% of cases.' Their
color depends on their adipocyte content and vasculariza-
tion: light brown or coffee colored when the gland is very
fatty, and darker, buff, or reddish brown when the gland is
more cellular or has a richer blood supply. They are soft and
supple and retain their original shape during dissection. If
FIGURE 2-6. The two sites of lymphatic drainage of the thyroid. flattened by the development of a thyroid nodule, they can
The first site is the visceral compartment of the neck. The second become rounded again when detached from its surface.
site is the lateral cervical region. The boundary between the two Their average size varies from 5.25 x 3 x 1.28 mm to 5 x
sites is the carotid sheath. 3 x 1 mm, as reported by Gilmour and Martin'? and Wang,6
respectively. The average weight of a normal gland is 40 mg
(range, 10 to 78 mg). They are encapsulated and have sharp
thyroid (Fig. 2-6). The first site is the paraglandular space or outlines and a smooth, glistening surface. Parathyroid
middle or visceral compartment of the neck. The second site is glands have a particular affinity for fat and are often found
the lateralcervical region. The boundary between the two sites completely or partially embedded in a fatty globule. They
is the carotid sheath. In the visceral compartment, there are often have a fatty capsule over their surface like the crest of
two groups: (l) the prelaryngeal and pretracheal and (2) the a helmet. Characteristically, they can be separated easily
paratracheoesophageal. The prelaryngeallymphatic vessels from the adjacent fatty structures.
lie anterior to and above the isthmus and merge superiorly Whatever their size, shape, or color, the parathyroid
and laterally with the lymphatic vessels of the superior pole glands always share an encapsulated appearance, which
of the thyroid along the superior thyroid vessels to drain into gives them a proper shape, an ocher tint, and a soft elastic
the nodes of the lateral neck. The pretracheal lymphatic consistency. Fat is softer, paler, and straw colored, with no
vessels lie below the isthmus and merge inferiorly with the definite shape. Thyroid tissue is firmer, less homogeneous,
lymphatic vessels of the anterior and superior mediastinum. darker wine-red in color with bluish-gray tints, and often
The anterior boundary of the visceral compartment is the embedded in "padding." Lymph nodes are firmer, more
posterior surface of the prethyroid muscles, but sometimes rounded, less homogeneous, and white, dirty gray, or putty
node metastases may be found very anteriorly in the mid- colored, with black dots. Nodes are separated from the adja-
line, particularly just above the isthmus (Delphian lymph cent fat with greater difficulty. Lymph nodes are usually
nodes). The paratracheoesophageal lymphatic vessels lie multiple. Thymic tissue is paler, grayish yellow or grayish
along the lateral and posterior aspects of the thyroid gland pink, granular, and adherent to the fat.
and along the course of the recurrent laryngeal nerves. They The arterial supply of the parathyroid glands is terminal in
communicate laterally with the lymphatic vessels in the type; the artery is solitary in two thirds of cases. The length
supraclavicular triangles and posteriorly with those around of the artery varies (l to 40 mm), but in cases of thyroidec-
and behind the trachea, the larynx, the pharynx, and the tomy, even if the parathyroid is pedicled, its preservation
esophagus. Lymphatic drainage of the isthmus flows down depends primarily on the distance between the origin of its
into the mediastinal nodes and upward into the paralaryn- artery and the thyroid capsule. The vascularization of P III
geal nodes. The normal flow direction from the central and depends primarily on the inferior thyroid artery. The P IV
lower parts of the lateral lobes is toward the tracheo- are supplied by the inferior thyroid artery, by the posterior
esophageal nodes. Only lymphatic drainage of the superior branch of the superior thyroid artery, or by the posterior
poles of the lobes may flow directly into the lateral neck marginal arch of Evans. Both P III and P IV may be entirely
nodes. This may explain why papillary thyroid carcinomas dependent on the inferior thyroid artery. Therefore, during
revealed by metastatic laterocervical lymph nodes are thyroid lobectomy, the inferior thyroid artery must never be
located in the upper pole of thyroid lobes in nearly two thirds ligated at the level of its main trunk. Similarly, the preserva-
of cases.'? Therefore, the central neck area is the primary tion of P IV requires separate ligation of the branches of
zone of lymphatic drainage for all thyroid cancers except the superior thyroid artery so as to preserve the posterior
those located in upper poles of the glands. Lateral neck areas branch. At the lower poles of the thyroid lobes, the preser-
(internaljugular chains and posterior triangles) are secondary vation of P III is ensured by the technique of ultraligation
 Surgical Anatomy and Embryology of the Thyroid and Parathyroid Glands - - 15

advised by Halsted and Evans." When the lower parathy- 8. Henry JF, Denizot A. Anatomic and embryologic aspects of primary
hyperparathyroidism. In: Barbier J, Henry JF (eds), Primary
roid glands (P III) are situated in the thyrothymic ligaments Hyperparathyroidism. Paris, Springer-Verlag, 1992, p 5.
or in the upper poles of the thymus, they are supplied by the 9. Thompson NW. Surgical anatomy of hyperparathyroidism. In:
inferior thyroid artery. Rothmund M, Wells SA Jr (eds), Parathyroid Surgery. Basel,
Venous drainage occurs by three methods: (1) by the Switzerland, Karger, 1986, p 59.
capsular network of the thyroid, (2) by the venous pedicles 10. Wang CA. Hyperfunctioning intra-thyroid parathyroid gland: A
potential cause of failure in parathyroid surgery. J R Soc Med
of the thyroid body, or (3) by a combination. Thyroid lobec- 1981;74:49.
tomy may render the ipsilateral parathyroid glands I I. Wheeler MH, Williams ED, Wade JSH. The hyperfunctioning intrathy-
ischemic. Hemostasis of a parathyroid vein generally should roid parathyroid gland: A potential pitfall in parathyroid surgery. World
be avoided because of the risk of glandular infarction. J Surg 1987;11:110.
12. Gilmour JR. The embryology of the parathyroid glands, the thymus,
Parathyroid ischemia is often evidenced by progressive
and certain associated rudiments. J Pathol Bact 1937;45:507.
darkening of the gland. Incision of the capsule and superfi- 13. Numano M, Tominaga Y, Uchida K, et al. Surgical significance of
cial parenchyma may prevent venous stasis and allow the supernumerary parathyroid glands in renal hyperparathyroidism,
gland to recover its normal color. World J Surg 1998;22:1098.
14. Pattou NF, Pelissier LC, Noel C, et al. Supernumerary parathyroid
glands: Frequency and surgical significance in treatment of renal hyper-

Summary parathyroidism. World J Surg 2000;24: I330.

15. Curley IR, Wheeler MH, Thompson NW, Grant CS. The challenge of
the middle mediastinal parathyroid. World J Surg 1988;I2:8 I8.
The thyroid gland is made up of follicular and parafollicular 16. Udekwu AG, Kaplan EL, Wu TC, et al. Ectopic parathyroid adenoma
of the lateral triangle of the neck: Report of two cases. Surgery
cells of endoderm and neural crest origin, respectively. The
1987;101:114.
lower parathyroid glands and thymus arise from the dorsal 17. Lack EE, Delay S, Linnoila RI. Ectopic parathyroid tissue within the
part of the P III, and the upper parathyroid glands arise from vagus nerve. Arch Pathol Lab Med 1988;112:304.
the P IV. The lower parathyroid glands are usually situated 18. Raffaelli M, Defechereux T, Lubrano D, et al. Intravagal ectopic
caudal to where the inferior thyroid artery and recurrent parathyroid gland. Ann Chir 2000;125:961.
19. Joseph MP, Nadol JB, Goodman ML. Ectopic parathyroid tissue in the
laryngeal nerve cross. If not situated here, they are usually hypopharyngeal mucosa (pyriform sinus). Head Neck Surg 1982;5:70.
in the thymus. The upper parathyroid glands are more dorsal 20. Lennquist S, Cahlin C, Smeds S. The superior laryngeal nerve in thy-
or posterior, more consistent in position at the level of the roid surgery. Surgery 1987;102:999.
cricoid cartilage. When not situated here, they may descend 21. Cernea CR, Ferraz AR, Cordeiro AC. Surgical anatomy of the superior
along the esophagus into the posterior mediastinum. An laryngeal nerve. In: Randolf GW (ed), Surgery of the Thyroid and
Parathyroid Glands. Philadelphia, WB Saunders, 2003, p 293.
understanding of the embryonic formation of the thyroid 22. Reed AE Relations of inferior laryngeal nerve to inferior thyroid
and parathyroid glands as well as experience helps the sur- artery. Anat Rec 1943;85:17.
geon recognize not only the normal relationship of the thy- 23. Randolf WR. Surgical anatomy of the recurrent laryngeal nerve. In:
roid and parathyroid glands with the adjacent structures but Randolf GW (ed), Surgery of the Thyroid and Parathyroid Glands.
Philadelphia, WB Saunders, 2003, p 300.
also the aberrant development or position of these glands. 24. Henry JF, Audiffret J, Denizot A. The nonrecurrent inferior laryngeal
This knowledge is of paramount importance for successful nerve: Review of 33 cases, including two on the left side. Surgery
operations. 1988;104:977.
25. Katz AD, Nemiroff P. Anastomoses and bifurcations of the recurrent
laryngeal nerve: Report of II 77 nerves visualized. Am Surg 1993;
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26. Thompson NW. In discussion of article Reference 24. Surgery
I. Le Douarin N, Le Lievre c. Embryologie experimentale: Demonstration 1988;104:983.
de I'origine neurale des cellules a calcitonine du corps uItimobranchial 27. Proye CAG, Carnaille BM, Goropoulos A. Nonrecurrent and recurrent
chez I'embryon de poulet. Comptes rendus de l'Academie des Sciences inferior laryngeal nerve: A surgical pitfall in cervical exploration.
1970;270:2857. Am J Surg 1991;162:495.
2. Pearse AGE, Cavalheira AE Cytochemical evidence for an ultimo- 28. Sanders G, Uyeda RY, Karlan MS. Nonrecurrent inferior laryngeal
branchial origin of rodent thyroid C cells. Nature 1967;214:929. nerves and their association with a recurrent branch. Am J Surg
3. Meyer JS, Steinberg LS. Microscopically benign thyroid follicles 1983;146:501.
in cervical lymph nodes. Cancer 1969;24:302. 29. Raffaelli M, Iacobone M, Henry JE The false nonrecurrent inferior
4. Gilmour JR. The gross anatomy of the parathyroid glands. J Pathol Bact laryngeal nerve. Surgery 2000; I28: 1082.
1938;46:133. 30. Henry JF, Denizot A, Bellus JE Papillary thyroid carcinomas revealed
5. Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human by metastatic cervical lymph nodes. Endocr Surg 1992;9:349.
parathyroid glands. Surgery 1984;95:14. 31. Noguchi S, Noguchi A, Murakami N. Papillary carcinoma of the
6. Wang CA. The anatomic basis of parathyroid surgery. Ann Surg 1976; thyroid: I. Developing pattern of metastasis. Cancer 1970;2:1053.
183:271. 32. Gilmour JR, Martin WJ. The weight of the parathyroid glands. J Pathol
7. Fraker DL, Doppman JL, Shawker TH, et al. Undescended parathyroid Bact 1987;34;431.
adenoma: An important etiology for failed operations for primary hyper- 33. Halsted WS, Evans HM. The parathyroid glandules: Their blood
parathyroidism. World J Surg 1990;14:342. supply and preservation. Ann Surg 1907;46:489.
 Medical and Surgical
Treatment of Endemic Goiter
Polly S-Y Cheung, MBBS(HK)

Endemic goiter is a preventable disease caused by iodine through school for studies on baseline health parameters and
deficiency. According to statistics from the World Health results of public health programs.
Organization (WHO) in 1999, a total of 740 million Endemic goiter is the chief consequence of iodine defi-
people-about 13% of the world's population-are affected ciency, resulting from either low iodine intake or ingestion
by endemic goiter alone. ' of goitrogens. The effects of iodine deficiency on human
Clinically, the individual with endemic goiter may present growth and development are denoted collectively as IDDs
with a diffuse to multinodular goiter. Biochemically, the (Table 3-1). 4 It affects all stages of development from fetus
urinary iodine excretion level is low, and the serum thyroxine and neonate to infant, child, and adolescent. Severe iodine
(T4) level may be low or normal with an elevated thyroid- deficiency affects the developing central nervous system.
stimulating hormone (TSH) level. Long-standing goiters may In the fetus, it causes abortion, stillbirth, congenital anom-
become autonomous in function and produce toxicity. alies, or cretinism. In children and adolescents, it produces
Mechanical obstruction to the trachea and the thoracic inlet and problems ranging from mild intellectual impairment to
malignant changes are possible sequelae of endemic goiters. mental retardation to full-blown endemic cretinism. It is
The occurrence of endemic goiter is preventable by an well recognized that a marginal iodine intake is associated
adequate supply of iodine in the diet. Universal salt iodina- with some degree of motor deficit or developmental delays,
tion is the goal of WHO in an attempt to eliminate the disease such as poor hand-eye coordination and impaired intellectual
by the year 2000. Data from WHO in 1999 showed that 68% performance exemplified by a reduction in IQ scores by as
of the total population in countries affected by iodine defi- much as 10 to 15 points in tests of mental development.'
ciency disorders (IDDs) have access to iodized salt. Existing
endemic goiters are currently treated with iodine supplemen-
tation to reverse hypothyroidism and to reduce the size of the Prevalence
goiters. For long-standing goiters, the treatment is the same
as that for sporadic goiter: T4 therapy and thyroidectomy are According to a global review in 1999, more than 2 billion
used for treatment; radioiodine therapy is used selectively. people are at risk for iodine deficiency, this number
Goiter, an enlargement of the thyroid gland, is conven- representing 38% of the world's population. Approximately
tionally called an endemic goiter when it occurs in more 741 million people from 130 countries have endemic goiter,
than 10% of the population in a defined geographic area; the representing 13% of the world population (Table 3-2).'
area is called an endemic area? A total goiter rate of 5% or Most of the world's natural supply of iodine exists in
higher is now recommended as the cut-off point to indicate the ocean as iodide. In high, mountainous areas and inland
a public health problem, following a decision made by the waters, the soil becomes leached of iodine by snow water
WHOlUnited Nations International Children's Emergency and glaciation. Lowlands with heavy rainfall or flooding can
Fund (UNICEF)/lnternational Council for the Control of also become iodine deficient. The most important goitrous
Iodine Deficiency Disorders (ICCIDD) Consultation on areas historically include the northern and southern slopes
IDD Prevalence in November 1992.3 This recommendation of the Himalayas, the Andean region of South America, the
is based on the observation that goiter prevalence rates European Alps, and the mountainous areas of China. Goiters
between 5% and 10% may be associated with a range of also occur in lowlands far from the oceans, such as the
abnormalities, including inadequate urinary iodine excretion central part of Africa and, to a lesser extent, in the coastal
or subnormal levels of T4 among adults, children, and areas of Europe."
neonates. Epidemiologic studies are usually carried out in The global prevalence of goiter has hardly increased at
school-age children (6 to 12 years of age) because of their the global level from 1990 to 1998 (Table 3-3),1 This figure
high physiologic vulnerability and their accessibility was thought to reflect the vigorous efforts in survey and
16
 Medical and Surgical Treatment of Endemic Goiter - - 17

increased data, especially in countries in the Eastern

Mediterranean, Africa, and Europe, where the total goiter
rate is high. The Eastern Mediterranean region has the
highest goiter prevalence rate, with 74% of the population at
risk for iodine deficiency. On the other hand, IDD prevalence
has decreased slightly in the Americas, Southeast Asia, and
the Western Pacific, reflecting the impact of IDD control
programs, especially salt iodization, on the population.
Southeast Asia and the Western Pacific (including China)
together account for more than 50% of the world's total
population at risk for IDD (Fig. 3-1). Countries in this
region, including India, Pakistan, Bangladesh, Nepal,
Myanmar (Burma), Vietnam, and Thailand, share a large
rate of prevalence of IDD; 599 million people are at risk and
172 million are goitrous. China alone has 300 million people
at risk of IDD because of the extensive mountainous areas in
that country, with 109 million suffering from goiter.8
Iodine deficiency persists mostly in developing countries
despite the established benefits of iodine supplementation in
the prevention of endemic goiter. In decreasing order of
magnitude, the number of people at risk of IDD is largest in
the Eastern Mediterranean, followed by Africa, Southeast
Asia, Europe, Western Pacific, and the Americas (see
Table 3-2).
18 - - Thyroid Gland

FIGURE 3-1. Prevalence of iodine deficiency disorders (IDDs)-global distribution. TGR = total goiter rate. (From WHOIUNICEFI
International Council for the Control of Iodine Deficiency Disorders. Global Prevalence of Iodine Deficiency Disorders. Geneva,
Switzerland, World Health Organization, 1996.)

Mild to moderate iodine deficiency still persists in a Iodine intake is considered adequate when it is between
number of European regions, namely Italy, Spain, Germany, 100 and 200 ug/day (Table 3-4). The principal source of
Greece, Romania, Hungary, Poland, and the former iodine intake is from diet or pharmaceuticals. I I
Yugoslavia." Continuous measures to provide iodine are The highest amounts of iodine in food are found in fish,
required to overcome the socioeconomic and cultural limita- seafood, and seaweed. Iodine is also found to a lesser extent in
tions in different regions. milk, eggs, and meat from animals whose diet contained suffi-
The prevalence of endemic goiter is influenced by age cient amounts of iodine. Fruits and vegetables, except spinach,
and gender. In severely iodine-deficient areas, goiter appears generally have very low iodine contents. The iodine content of
at an early age, and the prevalence increases markedly drinking water is too low to serve as a consistent contributor to
during childhood and attains its peak during puberty. From iodine supply.12 In an iodine-deficient environment, the locally
the age of 10 years, the prevalence is higher in girls than in grown food will also have a low iodine content. Some foods,
boys, probably because of the difference in metabolism of beverages, and drugs, such as multivitamins, minerals, and
iodine during adolescent growth. In both sexes, goiter preva- antacids, have coating or coloring agents that contain iodine.
lence decreases during adulthood, but the decline is sharper
in men than in women. 10

Etiology of Iodine Deficiency

Iodine is an essential substrate in the synthesis of the thyroid
hormones i.-thyroxine (T4) and t-triiodothyronine (T 3) .
The normal human thyroid gland releases about 65 ug of
hormonal iodine to the circulation per day, which represents
the minimum daily requirement of iodine. Iodine require-
ments increase during puberty, pregnancy, and lactation.
 Medical and Surgical Treatment of Endemic Goiter - - 19

Low supply of dietary iodine is the main cause of devel- Pathophysiology of Endemic
opment of endemic goiter. Because it is difficult to measure
the iodine content of foods, the adequacy of dietary iodine is Goiter
usually determined by the measurement of urinary excretion
Endemic goiter is the end result of the physiologic and mor-
of iodine. This measurement represents the ratio between
phologic changes in the thyroid gland as an adaptation to
concentrations of iodine and creatinine in casual urine
an insufficient supply of dietary iodine. When iodine intake
samples. 13 Two or more casual urine samples from the same
is low, thyroid hormone synthesis is impaired. This impair-
individual taken on consecutive days are recommended to
ment leads to an increased thyroidal clearance of iodide
allow for variation in creatinine content." Experience has
from the plasma and decreased urinary excretion of iodide,
shown that the iodine concentration in early-morning urine
an adaptation toward iodine conservation.
specimens adequately reflects an individual's iodine status.
T3, being three to four times more potent than T 4 but
In addition, iodine concentration per liter of urine bears a 1:I
containing only three fourths as much iodine as T 4, is
relationship with iodine per gram of creatinine and is now
adopted as the standard in field studies by WHO.3 Measuring preferentially synthesized over T 4 . There is also increased
iodine concentration per liter of urine helps avoid the cum- peripheral conversion of T 4 to T321
bersome measurement and calculation of the iodine- Clinical euthyroidism is thus maintained, but biochemi-
creatinine ratio. In nonendemic areas, the urinary iodine cally the pattern of low serum T4, elevated TSH, and normal
measurement is at least 100 ug/L. Severe iodine deficiency is or supranormal T 3 is often found. 22 . 24 In severe thyroid failure,
considered to occur with a daily iodine excretion of less than such as that in endemic cretinism, serum T3and T 4 concen-
20 IlgIL; moderate deficiency, 20 to 49 IlglL; and mild defi- trations are low and serum TSH concentration is markedly
ciency, 50 to 99 IlgIL.15.16 The prevalence of endemic goiter elevated. In less severe thyroid endemism, serum T3 and
varies with the severity of iodine deficiency (Table 3-5). T 4 concentrations may remain normal. The serum TSH level
Increasing iodine consumption in endemic areas has may also be normal or moderately elevated, and there may be
resulted in a reduction in goiter prevalence. The persistence of an exaggerated TSH response to thyrotropin-releasing hor-
goiter in some areas with adequate iodine prophylaxis and the mone (TRH) simulation, implying an increase in the pituitary
unequal geographic distribution of goiter in iodine-deficient reserve of TSH and subclinical hypothyroidism.
areas suggest the existence of other goitrogenic factors. Such changes are thought to be mediated through an
Natural goitrogens were first found in vegetables of the elevation in the serum TSH level. However, a wide variation
Brassica family, including cabbage, turnips, and rutabagas. in the level of TSH has been observed in normal and
Their antithyroid action is related to the presence of thioglu- goitrous individuals in endemic areas.P Such dissociation
cosides, which, after digestion, release thiocyanate and between goiter size and biochemical findings suggests the
isothiocyanate. These compounds have goitrogenic actions po~sible role of circulating thyroid growth factors, such as
by inhibiting iodide transport in the thyroid gland. A particular epidermal growth factors, or an autoimmune process in the
thioglucoside, goitrin, is also found in the weeds growing in pathogenesis of goiter." Activity of thyroid growth-promoting
pastures in Finland and Tasmania. 17 i~unoglo~ulin (TGI) has been demonstrated in patients
Cyanoglucosides are another important group of naturally With sporadic and endemic goiter.'? However, conflicting
?ccurring goitrogens found in several staple foods in the trop- results were obtained, and the methods of detection of such
ICS, namely cassava, maize, bamboo shoots, and sweet pota-
activity have been criticized, with this uncertainty leaving an
toes. They are converted to the goitrogen thiocyanate after unsettled role of TGI in goitrogenesis.P-"
digestion. Flavonoids from millet, a staple food in Sudan, are
also known to have antithyroid activity. IS The consumption of
millet in Sudan and cassava in Zaire was found to aggravate Morphologic Changes in
the severity of the goiter endemism in these places.'? Endemic Goiter
Protein malnutrition coexists frequently with endemic
goiter. Studies of malnourished individuals in endemic areas An increase in thyroid gland mass often accompanies the
show alterations in thyroid morphology and functions, sug- physiologic changes in response to iodine deficiency.
gesting that malnutrition has a goitrogenic effect.P Generalized epithelial hyperplasia occurs, with cellular
20 - - Thyroid Gland

hypertrophy and reduction in follicular spaces. In chronic Stage III: very large goiter that can be recognized at a
iodine deficiency, the follicles become inactive and dis- considerable distance (Fig. 3-2)
tended with colloid accumulation. These changes persist Because of observer variation in the measurement of
into adult life, and focal nodular hyperplasia may develop, goiter by inspection and palpation, the WHOIUNICEFI
leading to nodule formation." Some nodules retain the abil- ICCIDD Consultation on IDD indicators in November 1992
ity to secrete thyroid hormone and form hot nodules. Others recommended a simplified classification of goiter by com-
do not retain this ability, become inactive, and form cold bining the previous stages la and Ib into a single grade
nodules. Necrosis and scarring result in fibrous septa, which (grade 1) and combining stages II and III into grade 2. 3 The
contribute to the formation of multinodular goiter. sum of grades 1 and 2 is taken as the total goiter rate. The
simplicity of this assessment allows for easy training of field
staff in public health surveys.
Clinical Presentation and • Grade 0: no palpable or visible goiter
Diagnosis • Grade 1: a mass in the neck that is consistent with an
enlarged thyroid that is palpable but not visible when
Goiter is classified according to the size of the thyroid gland the neck is in the neutral position; it also moves upward
on inspection and palpation, and the following grading in the neck as the subject swallows
system was proposed by WHO in 196032 : • Grade 2: a swelling in the neck that is visible when the
Stage 0: no goiter neck is in a neutral position and is consistent with an
Stage Ia: goiter detectable only by palpation and not enlarged thyroid when the neck is palpated
visible even when the neck is fully extended In areas of mild endemicity where the goiter rate is low
Stabe Ib: goiter palpable but visible only when the neck and goiters are generally small (i.e., grade 1 or bordering on
is fully extended either grade 0 or 2), interobserver variations can be as high
Stage II: goiter visible with the neck in the normal as 40%. Ultrasonography is therefore recommended by WHO
position; palpation is not needed for diagnosis as a safe, noninvasive method for providing a more precise
and objective measurement of thyroid volume than inspec-
tion and palpation."
The most common form of goiter in children is a diffuse
thyroid enlargement. Nodularity may occur at a young age,
and the finding of a small, solitary, palpable nodule in ado-
lescence is common. Some diffuse goiters persist into adult-
hood, or the main bulk of the goiter may be replaced by
multiple nodules that form a multinodular goiter, simulating
a bag of marbles on palpation.
Functionally, the individual often remains clinically
euthyroid despite biochemical evidence of hypothyroidism,
with low or normal serum T4 concentrations and minimally
elevated serum TSH levels. Scintigraphy of the thyroid in
endemic areas may show marked heterogeneity in the uptake
of radioiodine and formation of hot or cold nodules.
Autonomous function of the nodules leads to failure of 1311
or 1231 suppression with T 3 and absence of TSH response to
TRH. Hyperthyroidism in older patients with endemic goiter
may be precipitated by iodination and cause Jodbasedow
hyperthyroidism.>'
Endemic cretinism is a sequela of severe iodine defi-
ciency in which intrauterine growth is affected by deficien-
cies of maternal T4 and dietary iodine. The infant is born
with mental retardation and either (1) a predominantly neu-
rologic syndrome of hearing and speech defects and varying
degrees of characteristic stance and gait disorders or (2) pre-
dominant hypothyroidism and stunted growth. These
changes are preventable with iodine prophylaxis but are not
curable once they have occurred.
Mechanical problems often arise in patients with huge goi-
ters that cause tracheal deviation and compression. Large, sub-
FIGURE 3-2. Classification of goiter size. 1, Stage Ia: goiter pal-
pable but not visible. 2, Stage Ib: goiter visible when neck
sternal, or retrosternal goiter can cause venous congestion and
extended. 3, Stage II: goiter visible in normal neck extension. the development of collateral venous circulation on the chest
4, Stage III: goiter visible at a distance. (From Perez C, Scrimshaw wall (Fig. 3-3). Surgical treatment is indicated in such patients.
NS, Munoz JA. Technique of endemic goitre surveys. In: Endemic The presence of hard nodules suggests possible malig-
Goiter, Monograph Series No. 44. Geneva, Switzerland, World nant disease, although an increase in the number of thyroid
Health Organization, 1960, p 369.) cancers in endemic goiter remains controversial.v-"
 Medical and SurgicalTreatment of Endemic Goiter - - 21

Countries such as the United States, the United Kingdom,

New Zealand, Australia, the Netherlands, Norway, and
Sweden have completely eliminated IDDs.41 Difficulties in
implementation occur in countries where locally inexpensive
noniodized salt is available and government programs to
increase iodine consumption are lacking.
Iodination of vegetable oil is the principal alternative
used in developing countries and in areas where salt is not
customarily used, such as the New Guinea highlands.f It is
also used as a short-term intervention while an iodized-salt
program is being established. One intramuscular injection
containing 480 mg of iodine provides adequate amounts of
iodine for up to 3 years. Oral administration of iodized oil
has the advantage of avoiding injections, but its duration of
action is shorter and more variable, depending on absorption
of iodine through the gastrointestinal tract." An oral dose
of 1 mL (containing 480 mg of iodine) provides adequate
iodine for 1 to 2 years after a single administration.
An increased incidence of thyrotoxicosis occurs after
increased iodine consumption. This increase was observed
in Tasmania after bread iodination in 1966 and was most
evident in older people." The thyrotoxicosis was attributed
to the presence of autonomous nodules or underlying hyper-
thyroidism in persons with long-standing endemic goiters.
Overall, however, the long-term correction of iodine defi-
ciency not only abolishes endemic goiter but also reduces
the incidence of toxic nodular goiters. Therefore, the occur-
rence of thyrotoxicosis does not outweigh the enormous
benefits of iodine prophylaxis in endemic regions. However,
iodination does have some risk in individuals older than
45 years with goiter, because hyperthyroidism may develop.
FIGURE 3-3. Large goiter with thoracic inlet obstruction. (From At the World Summit for Children in 1990, which was
DeSmetMP. Pathological anatomy of endemic goiter. In: Endemic attended by 71 heads of state and government, WHO,
Goiter, Monograph Series No. 44. Geneva, Switzerland, World UNICEF, and ICCIDD established the target of virtual
Health Organization, 1960, p 338.) elimination of IDDs by the year 2000 and universal salt
iodination in affected countries by the end of 1995.45
Efforts have been made to reduce the cost of salt iodina-
Follicular and anaplastic carcinoma are more common in areas
tion by reducing the price of potassium iodate and the
of endemic goiter. The diagnosis is often delayed in such
manufacturing cost of the spray-mixing equipment for salt
patients because goiters are so common in iodine-deficient
iodination. At present, the cost of salt iodination is approxi-
areas. Fine-needle aspiration biopsy helps select patients for
mately $0.05 per person per year. Campaigns have been
thyroidectomy.'?
launched in affected countries to analyze the existence
and the severity of the problem and to convince govern-
Treatment and Prophylaxis ments, salt producers, and other relevant bodies of the cost-
effectiveness and benefits of salt iodination. Funds have
The occurrence of endemic goiter can be prevented by been raised to help developing countries start programs of
supplying an adequate amount of iodine in the diet and salt iodination.i"
eliminating goitrogens and malnutrition. A 1998 global survey by WHO reported that 85% of
Iodination of salt is the preferred method of prophylaxis the total number of countries affected by IDD have either
because salt consumption is consistent and universal, the formed legislation on salt iodization to start implementing
technology of iodination is simple, and its production is easy national plans for iodination of all salt and introducing leg-
to regulate. It was first successfully introduced in Switzerland islation to prohibit the sale of uniodized salt'? or have plans
and in the state of Michigan in 1921.38 Iodine in the form of of action for controlling IDD. Data also showed that of the
potassium iodide is added to table salt in varying amounts 5 billion people living in countries with IDD, 68% have
ranging from 1 to 10,000 parts of salt to 1 to 200,000 depend- access to iodized salt and 65% of these countries have labo-
ing on local factors such as customary consumption of salt. ratory facilities to monitor urinary iodine status and salt
Potassium iodate is preferred in humans because of its iodine levels. America is the region that is closest to virtual
increased stability." Epidemiologic surveys have confirmed elimination of IDD, with more than 90% of the total popu-
that there is a dramatic reduction in the prevalence of goiter lation consuming iodized salt.
and progressive disappearance of endemic cretinism within For the patient with hypothyroidism and endemic goiter,
several years after introduction of salt iodination programs." the functional and neurologic changes are irreversible.
22 - - Thyroid Gland

Iodine supplementation during the first 6 months of life, 3. WHOfUNICEFIICCIDD. Indicators for assessing iodine deficiency
however, has been shown to prevent some of the neurologic disorders and their control through salt iodization. Document WHOI
NUT/94.6. Geneva, Switzerland, World Health Organization, 1994.
problems and also to cause regression in the size of endemic 4. Hetzel BS, Dunn IT, Stanbury 18 (eds), The Prevention and Control of
goiter in young children and adolescents.f Iodine Deficiency Disorders. Amsterdam, Elsevier, 1987.
In adults with large, diffuse, or nodular goiters, T4 therapy 5. Fierro-Benitez R, et al. Long-term effects of correction of iodine
suppresses TSH secretion and in 50% to 87% of patients deficiency on psychomotor and intellectual developments. In: Dunn IT,
Pretell EA, Daza CH, et al (eds), Towards the Eradication of Endemic
causes involution of the hyperplastic tissue and a 20% Goiter, Cretinism, and Iodine Deficiency. Washington DC, Pan
decrease in goiter size." American Health Organization, 1986, p 182.
Surgical treatment is indicated in diffuse or nodular goi- 6. Kelly FC, Snedden WW. Prevalence and geographical distribution
ters in the following situations: (1) large size or increase in of endemic goiter. In: Endemic Goiter, Monograph Series No. 44.
size while the individual is receiving TSH suppression treat- Geneva, Switzerland, World Health Organization, 1960, p 27.
7. WHOfUNICEFIICCIDD. Global Prevalence of Iodine Deficiency
ment; (2) mechanical obstruction to the trachea, esophagus, Disorders. In: Micronutrient Deficiency Information System (MDIS),
or thoracic inlet, such as in retrostemal or intrathoracic No.1. Geneva, Switzerland, World Health Organization, 1993.
goiter; (3) toxic change; (4) suspected or proven malignant 8. Ma T, et al. The present status of endemic goiter and endemic cretinism
change; and (5) cosmetic reasons. Subtotal thyroidectomy, in China. Food Nutr Bull 1982;4:13.
9. Gaitan E, Nelson NC, Poole GV. Endemic goiter and endemic thyroid
near-total, and total thyroidectomy are acceptable opera-
disorders. World 1 Surg 1991;15:205.
tions, and the indications are the same as those for patients 10. Clements FW. Health significance of endemic goiter and related
with sporadic goiters.P conditions. In: Endemic Goiter, Monograph Series No. 44. Geneva,
Radioiodine therapy has been used to reduce the size of Switzerland, World Health Organization, 1960, p 235.
euthyroid goiters and to control toxicity in the presence of II. World Health Organization. Trace Elements in Human Nutrition and
Health. Geneva, Switzerland, World Health Organization, 1996.
autonomously functioning tissue in multinodular goiters.51•52 12. Koutras DA, Papapetrou PD, Yataganas X, et al. Dietary sources of
However, large doses of radioiodine are usually required iodine in areas with and without iodine deficiency goiter. Am 1 Clin
because of the low levels of uptake in these large multinodular Nutr 1970;23:870.
goiters, which are also more radioresistant than diffuse toxic 13. Bourdoux P, Thilly C, Delange F, et al. A new look at old concepts in
laboratory evaluation of endemic goiter. In: Dunn IT, Pretell EA, Daza
goiters." Surgical treatment is preferred for most patients
CH, et aI (eds), Towards the Eradication of Endemic Goiter, Cretinism,
because it eliminates the bulk of the goiter, corrects the func- and Iodine Deficiency, No. 502. Washington, DC, Pan American Health
tional abnormality, removes possible malignant neoplasms, Organization, 1986, p 115.
and avoids long-term complications of radioiodine therapy. 14. Furnee CA, van der Haar F, West CE, et al. A critical appraisal of goiter
assessment and the ratio of urinary iodine to creatinine for evaluating
iodine status. Am 1 Clin Nutr 1994;59: 1415.
15. Stanbury IB, Hetzel B. Endemic Goiter and Endemic Cretinism.
Conclusion New York, Wiley, 1980.
16. Gaitan E. Iodine deficiency and toxicity. In: White PL, Selvey N (eds),
Proceedings of the Western Hemisphere Nutrition Congress IV. Acton,
In conclusion, endemic goiter is preventable and is a public MA, Publishing Sciences, 1975, p 56.
health problem worldwide, affecting 13% of the world's 17. Gaitan E. Environmental Goitrogenesis. Boca Raton, FL, CRC Press,
population. Iodination is cost-effective, and although it 1989.
results in a transient increase in hyperthyroidism, overall the 18. Gaitan E, Lindsay RH, Reichert RD, et al. Antithyroid and goitrogenic
effects of millet: Role of C-glycosylflavones. 1 Clin Endocrinol Metab
benefits greatly outweigh the risks. Significant progress has 1989;68:707.
been achieved in a global effort in eliminating IDD in the 19. Vanderpas 1, Bourdoux P, Lagasse R, et al. Endemic infantile
last decade, with 68% of the 5 billion people living in coun- hypothyroidism in a severe endemic goiter area of Central Africa.
tries with IDD having access to iodized salt. The global rates Clin Endocrinol 1984;20:327.
20. Ingenbleek Y, Luypaert B, De Nayer P. Nutritional status and endemic
of goiter, mental retardation, and cretinism are falling.
goiter. Lancet 1980;I :388.
For established goiters, treatment with thyroid hormone 21. Greer MA, Grimm Y, Studer H. Qualitative changes in the secretion
is helpful in some patients in stabilizing or decreasing goiter of thyroid hormones induced by iodine deficiency. Endocrinology
size. Thyroidectomy becomes indicated for mechanical and 1968;83:1193.
cosmetic reasons or because of possible or documented 22. Delange F, Camus M, Ermans AM. Circulating thyroid hormones in
endemic goiter. 1 Clin Endocrinol Metab 1972;34:891.
malignancy. 23. Pharoah POD, Lawton NF, Ellis SM, et al. The role of triiodothyronine
(T3 ) in the maintenance of euthyroidism in endemic goiter. Clin
Acknowledgment Endocrinol 1973;2:193.
24. Bachtarzi H, Benmiloud M. TSH regulation and goitrogenesis in
The author is grateful to Mrs. Pat Soong for providing technical assistance severe iodine deficiency. Acta Endocrinol (Copenh) 1983;103:21.
in the preparation of the chapter and Ms. Veronica Chan for typing the 25. Weber P, Krause U, Gaffga G, et al. Unilateral pulsatile and circadian
manuscript. TSH release in euthyroid patients with endemic goiter. Acta
Endocrinol (Copenh) 1991;124:386.
26. Tseng YC, Burman KD, Schaudies RP, et al. Effects of epidermal growth
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I. WHOfUNICEFIICCIDD. Progress Towards the Elimination of Iodine 27. Medeiros-Neto GA, Halpern A, Cozzi ZS, et al. Thyroid growth
Deficiency Disorders (lDD). Document WHOINHD/99.4. Geneva, immunoglobulins in large multinodular endemic goiters: Effect of
Switzerland, World Health Organization, 1999. iodized oil. 1 Clin Endocrinol Metab 1986;63:644.
2. Delange F, Bastani S, Benmiloud M, et aI. Definitions of endemic goiter 28. Vitti P, Chiovato L, Tonacchera M, et al. Failure to detect thyroid
and cretinism, classification of goiter size and severity of endemias, and growth-promoting activity in immunoglobulin G of patients with
survey techniques. In: Dunn IT, Pretell EA, Daza CH, et aI (eds), Towards endemic goiter. 1 Clin Endocrinol Metab 1994;78:1020.
the Eradication of Endemic Goiter, Cretinism, and Iodine Deficiency, 29. Zakarija M, McKenzie 1M. Do thyroid growth-promoting
No. 502. Washington,DC, Pan American Health Organization, 1986,p 373. immunoglobulins exist? 1 Clin Endocrinol Metab 1990;70:308.
 Medical and Surgical Treatment of Endemic Goiter - - 23

30. Weetman AP. Is endemic goiter an autoimmune disease? J Clin prevention of endemic goiter and cretinism. In: Stanbury JB, Hetzel BS
Endocrinol Metab 1994;78:1017. (eds), Endemic Goiter and Endemic Cretinism. New York, Wiley, 1980,
31. Studer H, Peter HJ, Gerber H. Natural heterogeneity of thyroid cells: p 513.
The basis for understanding thyroid function and nodular goiter 43. Bautista S, Barker PA, Dunn JT, et al. The effects of oral iodized oil
growth. Endocr Rev 1989;10:125. on intelligence, thyroid status, and somatic growth in school-aged
32. Perez C, Scrimshaw NS, Munoz JA. Technique of endemic goiter children from an area of endemic goiter. Am J Clin Nutr 1982;35:127.
surveys. In: Endemic Goiter, Monograph Series No. 44. Geneva, 44. Connolly RJ, Vidor GI, Stewart JC. Increase in thyrotoxicosis
Switzerland, World Health Organization, 1960, p 369. in endemic goiter area after iodination of bread. Lancet 1970; 1:500.
33. World Health OrganizationlInternational Council for Control of Iodine 45. United Nations. World Declaration on the Survival, Protection, and
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34. Steward JC, Vidor GI, Butterfield IH, et al. Epidemic thyrotoxicosis in 46. Grant JP. Iodine Deficiency Disorders on the Run. New York, UNICEF,
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35. Wahner HW, Cuello C, Correa P, et al. Thyroid carcinoma in an 47. UNICEF. The State of the World's Children, 1995. Oxford, England,
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36. Harach HR, Escalante DA, Onativia A, et al. Thyroid carcinoma and 48. Hintze G, Emrich K, Kobberling J. Treatment of endemic goiter due
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37. Lowhagen T, Granberg PO, Lundell G, et aI. Aspiration biopsy cytology 49. Wilders-Truschning MM, Warnkrob H, Leb G, et al. The effect of
(ABC) in nodules of the thyroid gland suspected to be malignant. Surg treatment with levothyroxine or iodine on thyroid size and thyroid
Clin North Am 1979;59:3. growth-stimulating immunoglobulins in endemic goiter patients. Clin
38. Marine D, Kimball OP. Prevention of simple goiter in man. JAMA Endocrinol 1993;39:281.
1921;77: I 068. 50. Roher HD, Goretzki PE. Management of goiter and thyroid nodules in
39. Sooch SS, Deo MG, Karmarkar MG, et al. Prevention of endemic an area of endemic goiter. Surg Clin North Am 1987;67:233.
goiter with iodized salt. Bull WHO 1973;49:307. 51. Bockisch A, Jamitzky T, Derwanz R, et al. Optimized dose planning
40. Aykroyd WR. Endemic goiter. In: Conquest of Deficiency Disease: of radioiodine therapy of benign thyroidal disease. J Nucl Med
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 Sporadic Nontoxic Goiter
Maha AI-Fehaily, MD • Orlo H. Clark, MD

The term goiter (L. guttur, throat) refers to an enlarged Causes of Goiter
thyroid gland, but what constitutes "enlargement" is often
not clearly defined.' Goiters can be classified according to Several mechanisms, including the interplay of intrinsic and
prevalence of the disease, thyroid function, location of the extrinsic factors in the thyroid, cause goiter. The goitrogenic
thyroid (neck or mediastinum), morphology, or underlying process involves genetic, environmental, dietary, endocrine,
etiology (Table 4-1). and other factors. The most common worldwide cause of
Sporadic nontoxic goiter (SNG) may be diffuse or nodu- endemic nontoxic goiter, as mentioned earlier, is iodine defi-
lar, is associated with normal thyroid function, develops ciency. In patients with sporadic goiter, the cause is usually
in subjects living in an iodine-sufficient area, and does unknown. Sporadic goiter is a result of environmental or
not result from an inflammatory or neoplastic process.' genetic factors that do not affect the general population. The
Endemic goiter is present when more than 10% of the pop- various types of goiter are listed in Table 4-1.
ulation living in a specific geographic area have a goiter. The
term sporadic goiter is used in regions with normal iodine
intake and a lower prevalence of goiter. Worldwide, endemic
Genetic Factors
goiter is the most common endocrine disorder, occurring in
more than 850 million people, or 7% of the world popula- The thyroid gland contains a series of enzymes that are
tion. It occurs almost exclusively in the iodine-deficient essential for the biosynthesis and secretion of thyroid hor-
areas. Sporadic goiter affects about 5% of the adult popula- mones. A defect in any of these hormones can result in
tion in the United States.' diminished hormone synthesis and a condition of goiter for-
Sporadic nodular goiter is a common clinical entity. mation known as dyshormonogenesis. Because the defects
Patients often present with small, diffuse, or nodular goiters are inherited disorders, dyshormonogenesis is also known
or have a solitary palpable nodule. In addition, recent stud- as familial goiter. These enzyme defects may be partial or
ies using high-resolution ultrasonography and previous complete. Patients with a more severe enzymatic defect
autopsy studies document that up to 50% of the general pop- may develop goiter and cretinism early in life. When the
ulation have thyroid nodules, even when the thyroid gland is defect is partial or less severe, goiter often develops during
normal to palpation. In addition, about 50% of individuals adolescence or later in life, and these individuals are usually
with a solitary thyroid nodule to palpation have other euthyroid. Although familial clustering of goiter is well
smaller thyroid nodules by ultrasound examination." recognized, no simple mode of inheritance has been recog-
There are numerous unresolved issues regarding the eti- nized. Familial euthyroid goiter has recently been linked to
ology, natural history, evaluation, and optimal management a multinodular nontoxic goiter (MNG1) locus on chromo-
of persons with goiter' Goiter represents an impairment of some 14q.6,7 Concordance rates for simple goiter in female
the thyroid gland's function, growth, and size. The problems monozygotic twins have been reported higher than in female
that arise in patients with goiter include the following: dizygotic twins (42% and 13%, respectively)." The age-
• Growth of the gland causing compressive symptoms or adjusted cumulative risk for simple goiter from birth to age
cosmetic problems (Fig. 4-1) 43 years was 0.53 for female monozygotic twins and 0.18
• Development of subclinical or overt thyrotoxicosis or for female dizygotic twins." These facts provide evidence of
hypothyroidism a genetic component of the etiology of goiter.
• Risk of malignancy in nodular goiter Tissue refractoriness to thyroid hormones due to a
• Cretinism or congenital hypothyroidism, as occurs in thyroid-stimulating hormone receptor (TSHR) defect is a
as many as 10% of infants born in areas of severe rare cause of familial goiter. A germline mutation on codon
iodine deficiency' 727 of the TSHR gene on chromosome 14q31 is specifically
24
 Sporadic Nontoxic Goiter - - 25

The intake of an excessive amount of iodine inhibits

thyroid peroxidase and results in the Wolff-Chaikoff effect.
The normal gland is usually able to escape from this effect
by inhibition of iodide uptake so that the intrathyroidal
iodide level falls and organification resumes. However, in
some patients with underlying thyroid disorders, the thyroid
is unable to adapt to iodide excess and goiter and hypothy-
roidism ensue (iodide-induced myxedema). Patients at risk
of goiter and or hypothyroidism due to failure to escape
from iodine inhibition of thyroid hormonogenesis are those
with Hashimoto's thyroiditis or those with reduced or
damaged thyroid tissue after thyroidectomy or after radia-
tion exposure to the neck. 15•16 Excess iodine intake in
contrast media may also cause goiter with hyperthyroidism
(Jodbasedow hyperthyroidism). Numerous medications
also have antithyroid and goitrogenic effects. Amiodarone,
which is rich in iodine (37%), has been associated with
induction of hypothyroidism and hyperthyroidism. Lithium
causes hypothyroidism by inhibiting (1) colloid formation
associated with toxic multinodular goiter.1O•11 Similar somatic stimulated by cyclic adenosine monophosphate and (2) the
cell mutations may activatean intrinsic growth control system release of thyroid hormone from the gland. Contrast media
leading to goiter. used for imaging are rich in iodine and may cause transient
hypothyroidism but not goiter. Ionizing radiation, either
Environmentally Induced Goiter externally or with therapeutic doses of radioactive iodine
(1 311), usually destroy thyroid tissue, causing hypothyroidism,
IODINE DEFICIENCY
but smaller doses (200 to 1500 rad) increase the risk of devel-
Endemic goiter is discussed in Chapter 3. An inadequate oping nodular goiter, thyroiditis, or thyroid cancer. I
adaptive mechanism of the thyroid to protect from severe
iodine deficiency results in the development of goiter. These
adaptive mechanisms include increased iodide clearance,
Pathogenesis
increased production of triiodothyronine (T3) relative to
Goiter Growth
thyroxine (T4 ) , and increased mass of thyroid follicular
cells. I Pregnancy increases the need for iodine and T4, Goiters result from focal follicular cell hyperplasia at one
which results from significant transfer of thyroid hormone or multiple sites within the thyroid gland. Iodine deficiency
from the mother to the fetus and also increased iodide loss works synergistically with other causes of goiter but does
in the urine. 12 Iodine-deficient thyroid tissue is more growth not appear to change the basic mechanisms of goitrogenesis.
responsive to thyroid-stimulating hormone (TSH) than is There is a positive correlation between the total DNA con-
iodine-replete thyroid tissue." Thyroid cellular growth is tent of the goiter and goiter weight. The increased amount of
also influenced by the higher human chorionic gonadotropin interstitial tissue and colloid formation usually contributes
serum concentrations that occur during pregnancy.14 little to the total goiter growth. An intrinsically abnormal
growth pattern of some thyroid cells is usually the driving
ENVIRONMENTAL AND OTHER FACTORS
force behind goiter growth. Heterogeneous subpopulations
The development of sporadic goiter is influenced by many of thyrocytes proliferate at different rates. Both extrathy-
factors. Thiocyanate is a well-known goitrogen produced roidal and intrathyroidal growth factors modulate goiter
from cigarette smoke and vegetable foods such as cassava formation. Under physiologic in vivo conditions, TSH is the
and cabbage. These goitrogens, however, seem to be of clin- most important stimulator of thyroid growth and function. A
ical importance only in areas of iodine deficiency. decrease in iodine intake leads to decreased synthesis and

FIGURE 4-1. Frontal (A) and side

(B) views of a 45-year-old man
with long-standing multinodular
goiter in an endemic area.

A B
26 - - Thyroid Gland

secretion of thyroid hormones. As a result, the serum TSH to be early mutations because they are present in both
level increases, stimulating thyroid growth.'? The increase benign and malignant thyroid nodules.
must be relatively short lived and intermittent because most Scarring, Necrosis, and Hemorrhage. For thyroid
patients have normal serum TSH levels. Other growth fac- nodules to grow, angiogenesis and new vessel formation are
tors are obviously involved since the sizes of various nodules required. These newly formed capillary vessels are often
vary considerably in the same patient. Furthermore, goiters fragile and are sometimes unable to adequately supply the
may grow despite administration of T 4 in doses that reduce growing thyroid tissue, This may result in areas of ischemic
the serum TSH level to a subnormal level or in patients with necrosis and hemorrhage within the goiter. Inflammation
toxic nodular goiter. Thus, thyroid growth-modulating and granulation tissue replace the necrotic areas, ultimately
factors in addition to TSH are involved in thyroid growth. resulting in fibrosis, scarring, and calcification. The result-
Some growth factors (e.g., insulin-like growth factor 1, epi- ing network of inelastic fibrous bands' connective tissue
dermal growth factor, and fibroblast growth factor) have a leads to nodularity because it interferes with smooth growth
growth-promoting effect, whereas others (e.g., transforming of thyroid parenchyma. 1
growth factor [TGF]-~ and activin A) inhibit growth.l"
Increased expression of ras and other protooncogenes may
Autonomy
also contribute to goiter growth.'?
Thyroid nodules that. function in the presence of a sup-
pressed blood TSH level are referred to as autonomous or
Nodule Formation
hot nodules. Autonomous function and autonomous growth
With increasing age, most thyroid glands and goiters mayor may not be related. Thus, cold nodules and hot
become nodular. Initially, many goiters are diffuse; however, nodules within a nodular goiter may have exactly the same
with intermittent stimulation, some diffuse goiters outgrow growth potential and may respond or be refractory to TSH-
their blood supply and become nodular (Fig. 4_2).20,21 Some suppressive T 4 treatment." Some thyroid follicular cells
thyroid cells are more sensitive to growth factors and take up and organify iodine in the absence of TSH, causing
become larger nodules. If these nodules trap and organify hot or autonomous nodules. As previously mentioned, these
iodine, the nodule may be "hot" or autonomous rather nodules usually have either TSHR mutations or, less com-
than "cold." Hot nodules are associated with TSHR and gsp monly, gsp mutations. When these nodules reach a certain
mutations. size and secrete increased amounts of thyroid hormone, the
In general, formation of thyroid nodules can be explained patient develops subclinical and then overt hyperthyroidism.
by the following mechanisms. This may occur either spontaneously or after exposure to an
Heterogeneous Subpopulation of Thyrocytes with excessive amount of iodine (Jodbasedow hyperthyroidismj.F
Different Proliferation Rates that Cause Focal
Hyperplasia or Nodular Transformation Time. Derwahl
and Studer investigated the pathogenesis of this heterogene- Natural History
ity and suggested that multinodular goiters are "true" benign
neoplasms due to intrinsically higher growth rates of some The natural history of nontoxic goiter varies. Children in
thyrocytes.Pr" However, most, but not all, nodules in a endemic areas generally have diffuse goiters, whereas
multinodular goiter are polyclonal when compared to true sporadic goiters tend to develop at an older age and tend to
neoplasms." Kopp and associates have also documented be nodular. Patients with multinodular goiter are usually
that both monoclonal and polyclonal nodules can be present older and have larger goiters than do patients with diffuse or
within the same multinodular thyroid gland." uninodular goiters. The growth rate of thyroid nodules is
Somatic Mutations and Clonality of the Thyroid usually slow, but some goiters increase up to 20% yearly."
Nodules. Different somatic mutations of the TSHR have Rapid growth of a nodule is usually caused by hemorrhage
been identified." Mutations in oncogenes such as ras appear or cyst formation. One must also be concerned about
malignant tumors such as a thyroid lymphoma or a poorly
differentiated or anaplastic cancer. Patients with goiters
appear to have a slightly higher risk of thyroid malignancy
(discussed later). Patients with multinodular goiters and
suppressed TSH levels are generally older and have a higher
plasma-free T 4 level and larger goiters than those with
multinodular goiters and a normal TSH. Up to 10% of
patients with euthyroid nodular goiter eventually develop
hyperthyroidism.P-'?

Intervention Versus Observation

Clear indications for operation (whether the patient is symp-
tomatic or potentially symptomatic) include the following:
FIGURE 4-2. Nodular goiter can involve either one or both lobes 1. Large goiter with obstructive symptoms such as short-
of the thyroid gland. ness of breath and dysphagia
Exploring the Variety of Random
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considerably to our left, to assist in the capture of the flying host. By
these various movements, the latter became so sensible of their own
inability to continue the conflict, but at a very unnecessary sacrifice
of human life, that after throwing away their arms, or rendering
them useless, they attempted to escape from our toils; but the great
proportion seeing that to be impossible, a white flag was at length
hoisted on the point of a sword, in token of submission. The
remainder continuing their retrograde movement across the
mountain, and the British troops being much in want of repose,
General Hill gave over the pursuit of the fugitives to General Morillo,
who followed them twenty miles—killed a number, and made many
prisoners.
Our loss in this admirably conducted affair, was extremely trifling,
compared with that of the enemy. We had only seven killed, fifty-
seven wounded, and one officer, Lieutenant Strenuwitz, aid-de-camp
to Sir William Erskine, missing.—That of the French, consisted of one
general (Brun), Colonel the prince D'Aremberg, two lieutenant-
colonels, an aid-de-camp of General Gerard's, thirty other officers,
and from thirteen to fourteen hundred non-commissioned officers
and soldiers prisoners. The whole of their artillery, money, baggage,
and provisions, also fell into our hands. Their loss in killed must have
been severe, for besides those who fell in action, Morillo found
upwards of six hundred dead in the woods and mountains, when in
pursuit of the remains of this little army, which in the action and
pursuit, was reduced from 3100 to 300, who with their wounded
chief, effected their escape.
The 18th regiment of Portuguese infantry, and Brigadier-General
Campbell's brigade of Portuguese infantry, having joined us at the
close of the action, these corps, together with General Long's
brigade of cavalry, and the 50th, 71st, and 92nd regiments of British
infantry, quitted the field of battle, immediately after the prisoners,
&c. were collected, and moved forward to St Pedro, two leagues
from Arroyo-del-Molinos.
We had not been long in camp, before a party of twenty-three
French dragoons were observed scampering across the plain in our
front, in the direction of Medellin. As no time was to be lost, one of
our cavalry piquets, consisting of seventeen men, dashed across the
plain to intercept them. In a few minutes the two parties stood in
the presence of each other, and without much ceremony, proceeded
to business. The action, however, was of short duration, for the
enemy, after a feebler resistance than was anticipated, agreed to
accompany our dragoons into camp, where they were received with
three hearty cheers. Both parties being in full view the whole time,
the scene was altogether extremely interesting.
At three o'clock in the morning of the 29th, we quitted our bivouac
at St Pedro, and after a march of fifteen hours, under torrents of
rain, entered Merida, wet, weary, and hungry. The following day
being one of rest, all the horses, mules, and asses, captured on the
28th, were sold by auction in the square of Merida, the produce of
which, together with the money found in Gerard's military chest, was
ordered to be divided at a subsequent period amongst the troops
actually engaged on that day.
Our mission into Estremadura being ended, the whole of the troops
in Merida, retired on the 31st to Montejo, and on the 1st of
November, to Campo Major. The distance being fully seven leagues,
we marched two hours before day-break, and at twelve o'clock,
halted to refresh the soldiers. Having a few minutes before crossed a
deep, rapid, narrow river, which struck some of our men a little
under the arm-pits, our situation at the time was not very
comfortable. However, a two hours rest, before a rousing fire, aided
by a glass of grog, and the rays of a powerful sun, soon banished all
traces of our ducking. In high spirits, therefore, we quitted our
temporary bivouac. But we had not proceeded above four hundred
yards, before another river, broader, deeper, and more rapid than the
other, crossed our path, and again drenched us to the neck. How we
came to halt in such a position, none could form any notion; but all
were agreed, that however amusing the spectacle of a few thousand
men standing in water to the neck may be to members of the
Quarter-Master General's department, those individuals must be told
that mistakes such as this cannot be tolerated, for to the weary, and
but too often heated pedestrians, duckings such as those just
mentioned, are the prolific sources of almost every disease, which
on service, hurries the young soldier into a premature grave.
We remained in Campo-Major on the 2nd of November, and on the
3rd moved to Arronches, an old fortress, the walls of which seemed
tottering to their base. Resuming our retrograde movement next
morning, we re-entered Portalegre about one o'clock, amid the loud
acclamations of a grateful and delighted populace. Satisfied that the
spontaneous and grateful effusions of the multitude on this occasion,
flowed from hearts untainted with hypocrisy, we received them as a
people's thanks—the noblest reward a soldier can receive.
Thus terminated our memorable trip into Spain, the success
attending which very far exceeded the expectations, either of the
noble individual who planned it, or the gallant and truly amiable
General who carried the plan into execution. And it is but justice to
the soldiers to state, that by a praise-worthy exercise of those
military qualities—patience, firmness, and valour, in a manner
peculiarly their own, their General was enabled to surmount every
obstacle which attempted to arrest his progress.
 CHAPTER V.
If General Gerard required evidence to convince him that it is easier
to prevent a surprise, than to banish the effects which are generally
produced by this worst of all military misfortunes, the issue of the
conflict on the 28th of October must have furnished him with proof
of the most ample description. Prolific as the page of history is in
examples of surprises of a similar nature, yet I doubt much whether
it affords one where the officer surprised, reposed in a more criminal
security than General Gerard did on the above occasion. When first
informed that the British troops were in motion, and advancing upon
the town in order of battle, the French chief who was then in bed,
raised himself on his elbow, and said to his informant, "Pooh, pooh,
the English troops will not march in such a morning as this!" and
then threw himself into his former position.
Almost the greatest military blunder which any officer can commit, is
that of allowing himself to be surprised. When a general loses a
battle, his honour and reputation remain unsullied, provided he has
discharged the duties of his office with fidelity and zeal. But the very
reverse befalls that general, who through carelessness, or a gross
dereliction of the duties confided to him, permits himself to be
surprised and beaten. Any general may have the laurel torn from his
brow, however conspicuous his military talents may be; but a
shameful defeat is rarely the reward of that individual, who, as far as
his means will permit, provides against every contingency; who
adopts every precaution in his power to prevent a surprise; and who
never for a moment leaves any thing to chance, lest fortune, if
trusted too far, may prove faithless; and, as in the case of General
Gerard at Arroyo-del-Molinos, entail on himself and followers, defeat,
and an overwhelming load of disgrace.
The military annals of the world exhibits to our view a long list of
commanders, who by forming too high an opinion of their personal
military qualifications, and spurning the advice of generals of inferior
rank, have placed themselves and followers in situations of imminent
peril. In this list, I fear we must insert the name of General Gerard.
At all events, his conduct at Arroyo-del-Molinos should serve as a
beacon to warn all officers of the dangers to be apprehended from
the smallest neglect of duty, from whatever cause it may arise, and
also to convince them of the folly of rejecting the advice of an
experienced or talented friend, simply because he may be junior in
rank to themselves.
The necessity of British troops being instructed in every description
of field and camp duty, previous to quitting their native shore, was
never more clearly developed than in our bivouac at Codeceira on
the 22nd of October. Our arms were no sooner piled, than the old
stagers flew like lightning through the woods in search of comforts.
But our poor Johnny Raws, as all young soldiers were denominated,
instead of imitating their brethren in their laudable vocation, formed
themselves into little groups, and seated on their knapsacks, sat
shivering in expectation that fire, water, and beef would be provided
them without any personal trouble. The fruits of this gross ignorance
of camp duty were soon obvious. In two hours the experienced
soldiers were called to dinner—the young ones had not then placed
their camp-kettles on the fire.
It would be an act of gross injustice, however, to throw the smallest
blame on the shoulders of those young men, for the ignorance
exhibited by them on that occasion. Totally uninstructed in field-
cookery, or any other portion of camp duty, what else could be
expected of them? But, should the British soldiers be longer
permitted to embark for a foreign clime in this state of ignorance?
Should they not rather be marched regularly as the state of the
weather will permit, to a convenient piece of ground in the vicinity of
their cantonments, then encamp, and after being instructed in every
description of camp duty which they can be called upon to perform
in the face of an enemy, return to their quarters in the evening.
Some such plan as this is indispensably necessary, for it is principally
owing to their total ignorance in the mode of cooking in the fields,
and sheltering themselves from the surly attacks of the mid-night
hurricane, that so many of our best and bravest spirits are hurried
into hospital in the early stages of a first campaign. Some individuals
would, no doubt, grumble and growl like bears at the new duty, but
these would always be few in number; for there are but few officers
or soldiers who would not willingly exchange a little inconvenience at
home, for health and some little comfort when roughing it at a
distance from their native land.
On crossing an extensive plain between Malpartida and Aldea-del-
Cano on the 27th of October, the troops were highly entertained by
the mounted officers of the corps, the latter having accidentally
started a hare, all the greyhounds belonging to the corps, were
instantly put in requisition to run down poor puss. The little, timid,
short-legged elf, ran hard for existence, but notwithstanding all its
arts and stratagems, it at length fell under the snouts of its
numerous pursuers. Perceiving that the soldiers were highly
delighted with the sport, the officers set about coursing in earnest,
and continued to amuse their companions, till they arrived at the
extremity of the plain. Trifling as this little piece of attention may
appear, it produced a much greater effect on the spirits of the men,
than the most sanguine promoter of the sport anticipated. Time was
so wonderfully beguiled, that on the arrival of the column at
Alcuesca, many of the men conceived that they had not marched
above half the distance they had really done. Should not this tend to
convince us that much good may at times be effected by the officers
finding harmless amusements for the soldiers under their command?
The 34th French infantry having preceded their commandant to the
field of honour at Arroyo, the latter who was still in his quarters
when we passed through the town, mounted his charger soon after,
and with his powerful arm raised for mischief, galloped along one of
the principal streets, resolved to rejoin it, or perish in the attempt.
Colonel Cadogan, 71st regiment, happening to be in the same
street, attempted to stop him, but in making a cut at the head of his
opponent, Cadogan completely neglected to guard his own, which
the former perceiving, returned the favour of his antagonist with
such effect, that, but for the tough materials surmounting it, the
head of Cadogan would have been severed in two. The gallant
Frenchman, however, was made prisoner, and having on various
occasions shewn a great deal of disinterested kindness to British
officers who had had the misfortune to be made prisoners, the same
marked attention was shewn to him at Portalegre. As a more
memorable reward for his humanity towards our countrymen, he,
soon after his arrival in England, received permission to return to the
bosom of his family in France. Were all officers to act a similar part
to those who fall into their hands, the horrors of war would be
considerably mitigated, and much of that ferocity which but too
frequently characterizes the actions of men in the field of strife,
would be altogether unknown.
The numerous escapes which soldiers have had from instant death
in the field of battle, would, if collected and published, form a most
interesting volume. Buttons, pen-knives, stocks, pencil-cases, keys,
watches, pocket-combs, sword-handles, and pieces of old paper,
would be found recorded as instruments made use of by Divine
Providence to prolong the lives of thousands of them. Amongst
those whose lives have been thus preserved by the kind interposition
of the Divine Being, I may name Colonel Cameron of the 92nd
regiment. The captain of the grenadier company of his regiment
having been wounded early in the action, the senior lieutenant, on
assuming the command of it, made a false movement, on perceiving
which, the Colonel greatly irritated, repeated his former orders in a
voice of thunder, and as was his usual custom when displeased, he
struck his left breast with his right hand, which then grasped the hilt
of his sword. The last syllable of his orders had just been delivered,
and his right hand had scarcely touched his breast, when a bullet,
dispatched by one of the enemy's riflemen, struck the Colonel on the
first joint of the middle finger, shattered the bone, passed through
the handle of the sabre, and then struck the breast so violently, that
he relinquished the command of the battalion to Major Mitchell, in
the full conviction that the ball had passed into his body. On being
undeceived, however, the gallant Colonel instantly rejoined his
battalion, and with his middle finger dangling by a small piece of
skin only, and the blood flowing from the wound in copious streams,
he remained at the head of his Highlanders to the close of the
engagement.
A few days previous to the battle of Arroyo-del-Molinos, a private
soldier of very weak intellect, named Brown, lost his firelock, but
where, or in what manner, he could give no proper account. On the
circumstance being reported to the commanding officer, he was so
enraged, that he ordered Brown to be taken into the first action
without arms. The captain of his company, however, feeling for the
situation of the poor fellow, ordered him to fall out when close to the
village of Arroyo. But no: the proud spirit of the half-witted creature
would not permit him to accept of the kind indulgence tendered him.
Brown continued in his proper place in the ranks, during the whole
of the engagement. Seeing some firelocks without owners, Captain
D—— desired Brown to arm himself with one of them, but the latter
replied, "Colonel Cameron having been pleased, Sir, to order me into
action without arms, here I will remain unarmed until the action is
over, or poor Jack Brown is sent into another world;" which
resolution the heroic simpleton faithfully kept.
 CHAPTER VI.
The commanding officer conceiving that five of us who had
accompanied the detachment from Ireland, properly belonged to the
2nd battalion, applied to Lord Wellington on our return to Portalegre,
for permission to send us home. Leave being granted, we, after
mutual expressions of regret, parted with our friends at Portalegre,
on the 22nd day of November, and proceeded to Gaffeta. Next day
we moved to Gavao, but finding an officer there taking quarters for
Colonel O'Callagan, and the first battalion, 39th regiment, we
departed instantly for Villa Franca, a small village two leagues from
Abrantes. On approaching the residence of the chief magistrate, in
order to procure billets, that worthy personage testified his joy at
our arrival, by throwing the door in our faces. Enraged at the insult
offered us, it is possible we might have adopted a summary mode of
obtaining an interview with this truly amiable personage, had not a
most interesting and lady-like woman introduced herself, and kindly
offered us all the shelter of her rural abode for the night. Having
previously invoked a blessing upon our patrona and her interesting
family, for her genuine hospitality, we bade adieu on the following
morning to the residence of this most excellent woman, and
proceeded to Abrantes.
After stowing away our baggage, and putting every thing in a fair
train for dinner, we strolled about the streets and ramparts of
Abrantes for a couple of hours, and then returned to head-quarters,
where we fancied a nice dish of soup and a beef-steak would greet
our return. Our disappointment therefore may be more easily
conceived than described, when I state, that instead of such
excellent fare greeting our entrance, we were welcomed by two
servants with rueful countenances, and each relating, in a plaintive
strain, tales of woe, sufficient to melt a heart of adamant. Moving as
these were, however, they proved but a poor substitute for dinner.
To work, therefore, we went; and partly by threats, and partly by
entreaty, procured from the inmates a few culinary articles, which
they very kindly had refused our servants. Our disappointments,
however, were not yet at an end, for when every thing was ready,
the amiable couple refused us even a single piece of earthen-ware to
put it on. Had Cruickshank witnessed the infernal pair standing
sentry over their stone-ware, the wife at one cupboard, and the
husband at the other, he must have acknowledged that a finer
subject for his pencil was never afforded, for truly they had more
resemblance to the inhabitants of Pandæmonium, than of this world.
After disposing of our baggage animals, we embarked at Abrantes in
a small commissariat boat on the 26th, and with a gentle breeze,
glided down the surface of the majestic Tagus, till the shades of
night made it dangerous to proceed farther. On arriving at a point
opposite to the neat, clean village of Chamusca, we hauled our boat
ashore, and proceeded to the town, where we were treated with
true hospitality. On the following day we dropped down to Valada,
where, on the 28th, we embarked in a large boat, and after
spending a rather uncomfortable night, landed at day-break next
morning, at the Black Horse Square in Lisbon.
On the 2nd of December, thousands of hand-bills were circulated in
Lisbon, intimating that at one o'clock on the following day, a British
officer, accoutred in cork-boots, would walk across the Tagus, from
Fort Belem, to the nearest point of land on the opposite shore.
Conceiving this to be the project of some hair-brained or unfortunate
individual, who, tired of life, was about to solicit the assistance of old
Neptune to carry him into another world, I walked down to Belem to
view the sports of the day. By eleven o'clock, the various streets
leading from the city to Belem, were literally crammed with people of
all nations and conditions, from the peer to the peasant, hurrying
along to the starting-post, some on foot, and the rest on every kind
of conveyance, from the humble donkey, to the carriage-and-four.
Being admitted into Belem Fort, I had a fine view of almost every
person, place, and thing in the vicinity. The Fort was filled to an
overflow with officers and ladies. Belem Castle was crowded with
Portuguese nobility and gentry, and the whole space around, and
between these two places, was completely covered with carriages,
equestrians, and pedestrians. Of the former, I at one time counted
four hundred and fifty. The river, for a considerable distance around
the spot whence the hero was to start, was covered with hundreds
of boats, carrying immense numbers of ladies and gentlemen, a
great proportion of the latter wearing the naval and military uniforms
of Old England. Six, eight, and even ten dollars were given for the
hire of a boat from Lisbon, on this occasion—the ordinary fare of
which was only about two shillings.
As the hour of one was announced by the bell of an adjoining clock,
the dense masses on shore pushed and jolted each other so much,
in order to get a peep at the cork accoutred hero before he set out
on his perilous excursion, that the company of Portuguese militia
stationed to preserve an opening for the officer to get to the river,
kept their ground with great difficulty. Soon after one, a voice
announced the hero's approach, but the intimation was premature.
Two o'clock was chimed, still he was absent. Three o'clock was at
length tolled, but he was not forthcoming. Not long after this, the
people, whose appetites were getting a little keen, whetted, no
doubt, by the fresh breeze from the Tagus, began to steal slily away,
and by four o'clock the greater proportion of the immense multitude,
between forty and fifty thousand, had retired to their respective
domiciles, fully satisfied that they had been completely hoaxed, and
vowing vengeance on the British officer and his cork-boots.
Having received a letter of recal from my commanding-officer, I
parted with my friends of the second battalion on the evening of the
4th, and early next morning embarked at Belem, with a detachment
which had just landed from England, and after spending an
uncomfortable night, we landed at Valada next day at noon. On the
7th we marched to Santarem—on the 8th to Gallegao—9th to
Punhete—the 10th to Abrantes, where we halted the 11th and 12th.
On the 13th we proceeded to Gavao—the 14th to Gaffeta—and on
the following morning bade our companions in Portalegre all hail.
 CHAPTER VII.
The well picked bones of a Christmas goose had scarcely been
removed from our mess-table, when an orderly entered, and
announced the unwelcome intelligence that our attendance was
required at the alarm-post next morning before day-break,—and
worst of all, in light marching order. Had this personage been the
bearer of a warrant for the execution of the whole party, our
countenances could not have presented a more rueful appearance.
We could have wished the evil day put off for twenty-four hours, but
as any memorial to that effect would only have been productive of
further disappointment, we at once resolved to make a virtue of
necessity, and accordingly retired to our respective quarters, and
made the necessary preparations for another excursion into Spain.
A little before sun-rise on the 26th December, the whole of the
troops quartered in Portalegre bade a temporary adieu to that
friendly town, and in the evening our brigade occupied Codeceira.
Next day we moved to Albuquerque, and on the 28th quitted that
city for Merida. Two leagues from the former we passed to the right
of the Castle of Zagala, beautifully situated on the summit of a hill,
from which there is a delightful view of the surrounding country.
Three leagues farther we passed through the miserable village of La
Rocka, and on the western slope of an eminence, a few hundred
yards in front of it, we went into bivouac. General Dombrousky being
in possession of Merida, with a mixed force of 1500 men, General
Hill requested commanding-officers of corps to have their fires as
much under the hill as possible, in order to favour the design he
then meditated of taking the Pole napping. The object, though not
expressed, was so obvious to every one, that the order was readily
and most cheerfully obeyed.
Next morning at day-break we quitted our bivouac, and under cover
of a dense fog, moved towards the point of attraction. General Hill
not being aware that the enemy had, the previous evening, pushed
forward a party of 150 cavalry, and 300 infantry, to the village of La
Nava, about half-way between our bivouac and Merida, the cavalry,
under General Long, were permitted to precede the infantry some
miles. This movement turned out unfortunately; for General Long
being also in ignorance of the proximity of this body to his own,
came bump upon one of the enemy's videttes close to La Nava, and
made him prisoner, but not till by discharging his carabine he had
made his friends aware of the danger that threatened them. The
density of the fog at the time rendering it impossible for either party
to ascertain the other's real numerical strength, the French troops
rushed to arms, and in a few minutes were formed ready for action,
on an eminence in rear of the village; but the British cavalry halted
so long, that before General Long finally resolved to attack, the
favourable moment had fled—never to return.
The fog soon after this first collision began to disperse, which
enabled our advanced guard to get a peep of their opponents.
Continuing to clear away, General Long was at length enabled to
draw near to the enemy without any fear of being surprised.
Although formed in square, the General resolved to attack, and if
possible compel them to surrender; but the little band of French
infantry received his charge with firmness, and finally beat him off.
This success gave the enemy some idea of their own strength, for
they instantly commenced a retrograde movement towards Merida,
fully convinced, no doubt, that they could effect their escape, should
no other opponents take part in the deadly feud. Charge succeeded
charge,—but from each our cavalry were forced to retire with loss,
and without making the least impression on the little column. These
repeated assaults proving ruinous to us, the dragoons were ordered
to hang on the flanks of the retiring foe, and take advantage of any
opening that might occur, either from the inequality of the ground
over which he had to retire, or the fire of two pieces of artillery,
which latterly joined in the pursuit. Accordingly, a gap no sooner
appeared, than our cavalry instantly prepared to renew the assault;
but before any advantage could be taken of it, some other brave
spirits had stepped forward and filled it up. Not one of the enemy's
infantry ever once appeared to shrink from the terrible conflict; on
the contrary, the whole party, individually and collectively, exhibited
throughout the action a degree of coolness and firmness which none
but the truly brave can possess in the hour of danger. In the manner
now described the parties traversed several miles, till the French
being reinforced from Merida, our cavalry gave over the pursuit,
more than satisfied that a body of well-disciplined infantry, when
under the guidance of an officer of courage, experience, and
prudence, has nothing to fear from a body of cavalry of double their
numerical strength. In the evening our corps closed up, and
bivouacked in front of La Nava, and next morning moved forward to
Merida, which the enemy had precipitately evacuated during the
night, leaving behind them a considerable quantity of corn.
The conduct of the French captain and his little band at La Nava,
affords to all officers and soldiers one of the noblest examples for
imitation on record. It is when placed in situations such as this, that
the prudence of an officer, and the courage of himself and soldiers,
is put to the severest trial. It is on occasions of a similar kind that
the soldier who combats for honour and glory, possesses such
decided advantages over him whose mercenary propensities lead
him to look upon honour and military renown as secondary objects.
Bear this then in remembrance, my brave fellow-countrymen, that it
is when duty calls you to defend a post against great numerical
superiority, that your courage is put to the severest trial; but never
forget, that it is also on those occasions you may expect to reap the
richest harvest of military renown.
When honour does the soldier call
To some unequal fight,
Resolved to conquer or to fall,
Before his general's sight.
Advanced—the happy hero lives,
Or, if ill-fate denies,
 The noble rashness heaven forgives,
And gloriously he dies.
The 31st was a day of rest; but at day-break on the 1st of January
1812, the whole corps crossed the Guadiana, and moved towards
Almendralejo, where we expected our arrival would be announced
by a royal salute from the field artillery of the Count D'Erlon. For a
league and a-half our route led us over a very barren heath, then
across a large, rich, but partially cultivated plain. As the road
between these two places rises with a gentle acclivity for at least
five miles from the banks of the river, the leading battalions enjoyed
a delightful view of the long and party-coloured columns, as they
winded along the heath towards their destination; and I have no
doubt but the spectacle would have appeared still more gratifying,
could we have banished from our recollection the object of our
movement—the destruction of our fellow-creatures. But
notwithstanding this, shall I say, almost only draw-back to a military
life, we enjoyed the interesting scene while it lasted; and when
deprived of that, we jogged along the plain as cheerily and merrily,
as the fatiguing nature of the march would permit us, till our
proximity to the enemy told us to prepare for battle.
It was now one o'clock, and a dense fog so enveloped every
surrounding object, that it was quite impossible to discover any thing
beyond a few paces from where we stood. As this unfavourable state
of the atmosphere prevented General Hill from ascertaining whether
the enemy held possession of Almendralejo, with five hundred, or
twice as many thousands; the cavalry, a few pieces of artillery, and
the 1st brigade, moved towards the town in order of battle. We had
not proceeded far, when the cavalry came into contact with the
French piquets, which were instantly attacked and driven in. To be
prepared for whatever might occur, the rear brigades quickly moved
up on our left, and occupied the stations assigned them. When the
first collision took place, the French troops in Almendralejo were
busily engaged in preparing their dinners, and consequently had
their thoughts rivetted on something more palatable than either
gun-powder, bullets, or bayonets. Part of them instantly moved to
the support of the piquets, and the remainder retreated to a rising
ground in rear of the town. The former, on receiving a few shots
from our artillery, wheeled also to the right about, and in a few
minutes were alongside of their friends. On the re-union of the two
bodies, the whole retired towards a height a considerable distance
from the town, over which runs the roads to Villa-Franca, and
Fuente-del-Maestre. Our light troops pursued the fugitives closely,
skirmishing with them all the way, and we followed, in hopes that
the Count would make his appearance at the head of his corps,
ready to receive us. In this, however, we were disappointed, for on
the fog clearing away, we were sorry to find that he had withdrawn
to Zafra with the main body, leaving behind him a strong rear-guard
only to cover his retreat.
As the fog died away, the rain which began to fall about one o'clock,
continued to increase in violence, till about three, when one would
actually have supposed that it was falling from buckets. Under these
circumstances, night approaching, and there being no chance of
bringing the enemy to close quarter, General Hill gave orders for
strong piquets to be posted on all the roads around Almendralejo,
and the rest of the troops to march into the town—which were
obeyed with the greater cheerfulness, that not one of them had a
dry jacket or shirt on their backs.
On taking possession of the quarters allotted to another officer and
myself, the poor people instantly pointed to the dinners of seven
Frenchmen, which in their hurry, they had found it necessary to
leave behind in a stew-pan by the fire. Preferring, however, a little
tea, to a mess of beef, pork, beans, garlic, and oil, we desired the
family to make use of it themselves. Permission was no sooner
granted, than the contents of the stew-pan was emptied into a large
stone bason, into which, sixty fingers and thumbs were instantly
plunged, and then, grasping a piece of the delicious morsel, carried
to the mouth, streaming with grease, like as many candles receiving
a polishing touch at the hands of their maker. The scene was a
laughable one, but very short, for in two or three minutes not a
vestige of any part of the dinner was visible.
The enemy shewing a reluctance to retire from Villa-Franca and
Fuente-del-Maestre, two detachments were despatched from
Almendralejo on the 3rd of January to dislodge them. The one which
moved against Villa-Franca, consisted of the 9th and 13th light
dragoons, two pieces of artillery, the 50th, 71st, and 92nd
regiments, and 60th rifle company, and was commanded by Major-
General Howard. The other which was under the command of the
Honourable Lieutenant-Colonel Abercromby, 28th regiment, was
composed of the 2nd hussars, king's German legion, the 4th and
10th Portuguese cavalry, and 28th British regiment of infantry. Both
detachments moved from Almendralejo, at twelve o'clock. On a
height about half way between the latter place and Villa-Franca, we
first obtained a view of the enemy, drawn up on a commanding
piece of ground, a few hundred yards from the town, on the road to
Los-Santos. Soon after this, the detachment was formed into two
columns, the right composed of the 92nd regiment, 60th rifle
company, and one piece of artillery, was placed under Colonel
Cameron; and the left, which consisted of the remainder of the
detachment, was led by Major-General Howard in person. The left
column moved direct upon the town, in order to attack their right
flank and centre, while the right was to co-operate with the right
battalion of the left column, in its assault on the centre, if it could
not throw itself in rear of the left wing. The enemy not only
appeared prepared for a visit from us, but for some time gave most
unequivocal indications that they would pepper us well before they
retired. Indeed so satisfied were we all of this, that we looked
forward to a tight little affair with them. But appearances on this, as
on many former occasions, proved deceitful;—for just as we had
approached that point from which we intended to apply those
means, by which British soldiers are accustomed to remove every
obstacle which attempts to arrest their progress, the French chief
considering it imprudent to stake the fate of his little corps on the
issue of a brush with us, faced about, and walked off towards Los-
Santos, pursued by our cavalry.
Lest the enemy should attempt to pay us home in the coin of
Arroyo-del-Molinos, piquets composed of whole companies were
posted on every road branching from Villa-Franca. The rest were
thrown into the town, with orders to remain accoutred, to be ready
to turn out at a moment's warning, and to be on the alarm-post two
hours before day-break. From nine o'clock in the evening, till seven
o'clock on the following morning, rain and hail fell in such prodigious
quantities, and was forced to the earth with such violence by the
wind, which blew a perfect hurricane, that all those who were on
piquet, joined their battalions in the morning in a most deplorable
condition. One of the officers in particular, was to all appearance a
perfect maniac. Two hours before day-light, we who were in Villa-
Franca proceeded to the alarm-post, where, in ten minutes, we were
as thoroughly drenched as if we had just emerged from a six months
ablution in the Bay of Biscay. Never before did I witness such a
tempest. After a four hours exposure to its utmost fury, we departed
from Villa-Franca, and returned to Almendralejo.
The detachment under Colonel Abercromby was more successful in
killing and maiming than we were. On the road to Fuente-del-
Maestre, a French regiment of cavalry crossed the path of the
detachment. On coming in sight of the enemy, the 2nd German
dragoons flew at them like as many bull-dogs, and being supported
by the Portuguese, the enemy was defeated with the loss of twenty
killed and wounded, and thirty-one taken prisoners. Our loss was
trifling. This detachment also rejoined the main body on the 4th, and
the whole retraced their steps to Merida on the following day.
None but those who were present can have any idea of the fatigue
which the soldiers endured from the 1st to 5th January, from the
wretched state of the roads from Merida to Villa-Franca. On
returning to Merida, they had more the appearance of troops that
had been six months under canvass, than men returning to
cantonments after a ten day's campaign. On the marches of the 1st,
3rd, 4th and 5th, a great many of the soldiers sunk deep into clay of
such an adhesive quality, that in extricating themselves from its
grasp, many of them tore their gaiters to pieces, and some of them
actually left their shoes behind them, and trudged along in their
stockings. On these occasions I seldom had less than four pounds of
clay at my feet, which fatigued me so much, that on retiring to rest
each night, I dropped asleep without the aid of any stimulant. Such
then being my situation, who had neither musket, knapsack,
canteen, or haversack to carry, what must the soldiers have suffered
who had to march encumbered with all these, weighing altogether
nearly three stone?
To those who are eternally croaking about the half-pay and pensions
of those officers, non-commissioned officers and privates, who
served in the late war, I wish no greater punishment than to be
made to serve but one short campaign in a country where hardships
and dangers, similar to those the British troops encountered in
Spain, may stare them in the face at every step, and where their
only comforts, when summed up, may, as in the Peninsula, consist of
a daily allowance of one pound of tough beef, and a similar quantity
of hard biscuit; being well convinced that on their return to their
native land, they will have tasted so freely of the sweets of a
soldier's life, when engaged in the active operations of the field, that
they will be prepared to convert their hoarse murmurs of
disapprobation of the half-pay and pension-list, into a sweet-
sounding and rapturous applause.
In the suite of General Hill, on the 1st of January, moved the
Marquis of Alemeida, a Spanish nobleman, between fifty and sixty
years of age. Having suffered severely from French rapacity, the
Marquis, as may be supposed, was one of their bitterest enemies.
Being a warm admirer of the British character, he not only
accompanied us in all our wanderings, but laid aside his native habit,
and assumed the scarlet, in humble imitation of his friend, our
worthy General. In addition to a long scarlet coat, the Marquis
generally wore a cocked-hat, always decorated with one, sometimes
with two, and not unfrequently with three long red and white
feathers dangling to his shoulders, in as many different directions.
His appearance altogether was rather odd, but the singularity of his
costume soon ceased to attract notice, and in a little time he
became a considerable favourite with all classes.
On arriving in front of the enemy's piquets, the Marquis had no idea
that he was so close upon the enemy, until the unexpected
intelligence was announced to him by one—two—three from our
artillery, a few yards in front. Neither the worthy nobleman or his
horse being prepared to accede to this mode of conversing with the
plunderers of his estates, the former stared, and the latter reared
and plunged, as if anxious to get quit of its burden, fancying, no
doubt, that the Marquis was the sole cause of his being in such noisy
company. On the third gun being fired, the Marquis, with a
countenance which at once denoted the fervour of his prayer,
exclaimed,—"Oh, Jesus, Maria, Jose!" and then casting a glance
towards those around him, as much as to say, "I am off," put spurs
to his willing nag, which being as anxious to get out of the scrape as
its master, flew like lightning in the direction which it was supposed
the Marquis wished him, and in a twinkling both were lost to our
view in the fog.
A private soldier of the 28th regiment having sipped rather freely of
the juice of the grape, previous to our departure from Almendralejo
on the 5th of January, fell out of the ranks unperceived, laid himself
down to banish all traces of the copious draught, and enjoyed his
nap so comfortably, that night's sable shroud had shut every earthly
object from the view of man before he awoke. Alone, enveloped in
darkness, and in a part of the country totally uninhabited, the poor
lad frequently fancied during the stillness of the night, that he saw
his name as a deserter to the enemy, handed in to the Adjutant-
General—the members of the court-martial assembling to try him—
the sentence of death passed, and the provost-marshal at the head
of his party, ready to carry the sentence into execution. With such
thoughts as these darting across his mind, the victim of dissipation
rose from his cold and cheerless couch at dawn, on the 6th, and
bended his steps towards Merida. Afraid to join his corps, however,
the bragge slasher proceeded to a small village about three miles
from head-quarters on the opposite bank of the Guadiana, in hopes
that some humane individual would intercede for him at head-
quarters.
Receiving information soon after his arrival that there were two
French soldiers concealed in the village, the worshipper of Bacchus
proceeded with a few of the natives to their residence, and after
securing them, and fastening their hands, he marched them off in
triumph for Merida. Strolling on the bridge with a few friends, when
the trio were first observed, and considering it rather an odd
circumstance to see a British soldier marching two Frenchmen as
prisoners from the left bank of the Guadiana, where there were no
British soldiers then quartered, we inquired at the worthy Hibernian
where he became possessed of the friends in his company? Shewing
some disinclination to satisfy our curiosity, we repeated our query in
a more peremptory manner. We had scarcely done so, however,
when we perceived the poor man struggling hard to give utterance
to his inward thoughts, but notwithstanding his utmost exertions, he
could not utter a syllable, till his heart was relieved by a few pearly
drops trickling over his weather-beaten cheeks. On these drying up,
the repentant soldier related to us the foregoing particulars, and
then with a palpitating heart, (the vision of the previous night being
still before his eyes,) he moved into town with his prisoners. He was
of course placed in confinement, and but for this singular adventure,
would have paid dearly for his libations to Bacchus at Almendralejo.
If the various members of the British army would reflect for a
moment on the consequences which but too generally follow in the
train of dissipation, before seating themselves to taste the pleasing,
but intoxicating beverage, numerous crimes which now stain the
pages of the character-books of every regiment in the service, would
never be heard of. The conduct of the Macedonian conqueror on
various occasions, shews us to what a degrading condition this most
detestable vice sometimes reduces the most celebrated individuals,
and his death furnishes a memorable example, that dissipation
hurries all its votaries to the narrow house, without any regard to
age or station in society. On launching into the world, therefore, all
military men should ever be on their guard against the assaults of
dissipation, for by dipping deep into the cup of intemperance, they
will not only destroy their mental faculties, ruin their pecuniary
resources, as well as their constitutions, but may at length be led to
commit crimes, for which, like Alexander on the death of Clitus, they
may be made to suffer all the horrors which a conscience, burdened
with the murder of a fellow-creature, and that individual a bosom
friend, can inflict upon them.
 CHAPTER VIII.
Sir Rowland Hill having received an order early in the morning of the
12th of January, to retrace his steps to Portalegre, we marched from
Merida at nine o'clock, a.m. and in the afternoon bivouacked behind
La-Nava. Next evening we reposed on the bank of a little river, under
the castle of Zagala, and on the 14th returned to Albuquerque. We
retired to Alegreta on the 16th, and to Portalegre on the 17th. On
the succeeding day, the men were busily employed in renewing their
stock of clean linen; and on the 19th, we moved to Alpalhao, on our
way to the North, to tender Lord Wellington our assistance, should
his lordship require it. We reached Niza on the 20th, where, on the
following morning, we received the glad tidings of the fall of Ciudad-
Rodrigo. As Marmont, however, still shewed a disposition to give
battle, we advanced from Niza to the Tagus on the 25th, crossed
that river by a bridge of boats at Villa-Velha, and then moved two
leagues farther, and occupied a few miserable villages. Next day we
entered Castello-Branco, where we had the pleasure of meeting with
the French garrison of Ciudad-Rodrigo, on their way to British
transports.
Marmont having withdrawn his army to Salamanca, to wait an
opportunity of resuming the offensive, when his chances of success
should appear more inviting, we bade adieu to Castello-Branco on
the 1st of February, and retraced our steps as far as Villa-Velha,
where we bivouacked. On the 2nd, we occupied Niza, the 3rd
Alpalhao, and re-entered Portalegre the following morning.
The siege of Ciudad-Rodrigo, forms one of the most glorious
achievements of the late Peninsular war, and marks in an eminent
degree the consummate military talent of the General who brought it
to a successful conclusion.
The Marshals Marmont, Soult, and Suchet, viewing the inactivity of
the allied army in the latter months of 1811, as something
tantamount to an acknowledgment on the part of the British chief,
that he was not in a condition to undertake any offensive movement
of importance, formed a triple league, by which Marmont appears to
have agreed to favour his brother Marshals with a few of his
brigades during the winter months, on condition of receiving a
similar favour from them in the following summer. Marmont's
reinforcements quitted the banks of the Tormes and Tagus in the
end of November and beginning of December 1811, and moved
towards the seat of war in the east and south of Spain. On the
approach of their friends, Soult laid siege to Tariffa, and Suchet to
Valencia.
Having instantly discovered the deep game which his powerful
opponents were playing, Lord Wellington took measures to render it
a losing one. With the eye of the eagle, he watched their every
movement, but never attempted to derange their plans, or arrest the
progress of the brigades, till the latter had arrived at a point so
distant, that they could not return to the banks of the Agweda in
time to prevent his Lordship carrying into execution his designs upon
Ciudad-Rodrigo. But on Marmont's troops arriving at that point,
instructions were immediately transmitted to Sir Rowland Hill, to
carry into execution the first part of those admirably planned
operations, which terminated in the capture of that important
military post.
No better proof can be adduced of the ability with which the whole
of these operations were planned and executed, than the signal
advantages which resulted from them to the common cause. Sir
Rowland Hill's grand object in marching upon Merida, being to draw
the attention of the enemy to a point far distant from that to be
assailed, his movement was attended with all the success which
could have been anticipated, The Count D'Erlon no sooner heard of
our arrival on the banks of the Guadiana, than he withdrew
precipitately from Almendralejo, and for a day or two after,
dispatched a courier to Soult every two hours, soliciting immediate
assistance, otherwise he would be inevitably devoured by the
"Arroyo-del-Molinos devils," who were in close pursuit of him. Being
totally ignorant as to the number of "devils" that were following his
friend D'Erlon, Soult, on receiving a few of these applications for
succour, transmitted instructions to General Laval, commanding
before Tariffa, to raise the siege of that place, and at the expence of
all his battering-train, &c. fly with all possible celerity to the Count's
relief, which instructions were implicitly obeyed. From these
proceedings of the enemy in Andalusia, and the subsequent tardy
movements of Marmont on the side of Ciudad-Rodrigo, it appears
quite evident that the eyes of the two were rivetted too long upon
our movements, for before they recovered from the panic which our
march created amongst them, they thus allowed the British flag
proudly to wave over the turrets of Ciudad-Rodrigo.
With all deference to the experience and high military characters of
the three Marshals, it seems evident that their plan of operations
was based on a capital military error,—that of under-rating the
strength of their opponent. By adopting this view of Lord
Wellington's forces, Marmont denuded himself of the means of
affording the necessary protection to that portion of the Spanish
territory which his Imperial Master had placed under his charge, and
as a natural consequence of such conduct, lost possession of
Ciudad-Rodrigo. Soult, on the other hand, committed another error,
little inferior in magnitude to the one just mentioned, that of over-
rating the force under General Hill. By doing so, Soult not only raised
the siege of Tariffa in a disgraceful manner, but allowed his attention
to be completely abstracted from that point towards which the eyes
of every Frenchman in the Peninsula should have been directed.
These facts, I conceive, shew us the folly of any general either
under-rating or over-rating the numbers, courage, or discipline of an
opponent's forces. For although I most readily admit that it may be a
little difficult at times for a general to banish from his breast the
timidity of a Druet, who exaggerated the danger that threatened
him, or the temerity of a Marmont, who as much underrated them;
yet I am quite satisfied, that unless a general's experience and
knowledge of his duties are such as will enable him to steer clear of
timidity on the one hand, and temerity on the other, he should be
held incapable of conducting any field operation, if the result is
expected to have any influence on the issue of the campaign.
On passing a church one morning during our residence in Portalegre,
a melancholy sound struck my ear,—it was a funeral dirge. In a few
minutes the mournful procession entered the portal of the church,
and being anxious to observe the ceremony, I followed. Around the
bier stood an assemblage of priests and friars, who for a
considerable time chaunted hymns for the soul of the deceased. At
the conclusion of the service I stepped forward to view the coffin,
and the piece of inanimate clay it contained. The coffin being open, I
beheld a female figure laid out in the usual manner, with her face
uncovered, and decorated in a rich muslin dress. The countenance,
though then in ruins, exhibited marks of beauty. The junior priests
having removed the corpse to a grave dug for its reception in the
body of the church, the bottom of the coffin was withdrawn, when
the body descended into its place of repose, in a manner the most
revolting I ever witnessed. But distressing to the feelings as was this
disgusting mode of depositing the body of a fellow-creature in the
silent tomb, the subsequent operations of the sexton was ten times
more so. The latter, after sprinkling a little mould over the body,
instantly began to pound it with a log of wood, resembling a
paviour's mallet, and continued to do so, after every additional layer
of earth, till the whole of the latter had been so far replaced in its
original position, as to permit the flag which surmounted the grave
to be laid on a level with those around it. During the latter part of
the ceremony I remained close to the grave, gazing in silent
astonishment at the scene before me. At length, however, I was
roused from my reverie, by a most offensive effluvia proceeding
from the depository of the deceased. I did not, however, for some
time, desert the post which I had assigned to myself; but being at
length completely overcome, I made the best of my way towards the
door, lest the exertions of the grave-digger might impose on his
superiors the disagreeable duty of bearing me to my lodgings.
There being no places of public amusement in Portalegre, time, long
before the end of February, had become such a drug on our hands,
that the collective wisdom of the garrison was frequently reduced to
its last shift to devise a rational mode of employing it. Our walks
being few, and miserably bad, and having no books "save the
devil's," by scanning the pages of which we could hope to spend a
few hours each day with pleasure and advantage, not a few of the
idlers paid more visits to a place denominated hell, than were at all
profitable either for their purses or their morals. When officers are
once induced to give up their time to play, and employ all the
powers of their mind to gratify the low, grovelling ambition of
acquiring wealth at the expense of those whom they consider their
friends and brothers;—when the love of play leads officers to prefer
the amusements of the card and billiard-tables, and the rattling of
dice, to the faithful discharge of their public and private duties;
when they become so wedded to their favourite pursuits, as to
consider it a punishment to eat, drink, and sleep, they must be held
as totally useless to the service,—to be worthless members of
society,—the slaves of vice,—and of that low cunning and chicanery
which borders upon villany.
Accursed game! thy blight is every-where,
Thy lawless fingers pilfer every purse;
The smart mechanic, and the pamper'd peer,
Endure alike the pressure of thy curse.
When hopeless ruin hath dissolv'd thy snare,
The pistol or the bowl are things of course;
And few can from thy gripping fangs depart
Without a blighted name or broken heart.
 CHAPTER IX.
Lord Wellington having finally resolved upon the siege of Badajoz,
the advanced guard approached our cantonments on the 2nd of
March. Next day we moved forward to Alegreta, and on the 4th to
Albuquerque. Here we remained until every preparation was made
which our Generalissimo considered necessary to ensure the success
of the enterprise.
On the 16th of March we bade a final adieu to Albuquerque, and
with the exception of one Portuguese brigade, the whole of Sir
Rowland Hill's corps moved upon Merida. That evening we
bivouacked near Zagala, next afternoon at La Nava, and on the 17th
we entered Merida.
Sir Rowland Hill finding Merida in possession of a few of the enemy's
dragoons, and that the latter were supported by a battalion of
infantry, encamped about a mile from the town, on the opposite
bank of the Guadiana, gave orders to General Long to cross the river
a little below the bridge, with his brigade of cavalry, in order to
capture those of the enemy in Merida, and keep the infantry from
retreating too quickly, till we could get up to them. On the first
alarm, however, the French cavalry fled from Merida, some by the
bridge, others by a ford a little above it. The former, by discharging
their carabines on the bridge, gave their friends in the wood
intimation of their danger. As no time was now to be lost, the 1st
brigade, 50th, 71st, and 92nd regiments, moved towards the town
at a trot. In a few minutes we were on the bridge, and a few more
carried us across it. Here we halted a minute, and then renewed the
pursuit with renovated strength; but notwithstanding all our efforts,
and those of our mounted friends, to bring them to action, the
enemy retreated at such a goodly pace, that fast as our brigade ran,
the fugitives always continued to run faster. Success at length
appearing hopeless, and our men being completely blown, we gave
over the pursuit, and retraced our steps to Merida, carrying with us a
few prisoners, whose joints being less supple than their more
fortunate friends, were obliged to fall behind, and were consequently
taken.
Sir Thomas Graham crossed the Guadiana on the 16th, at the head
of the right wing of the covering army, consisting of the greater part
of the cavalry, the 1st, 6th, and 7th divisions of infantry, and then
directed his march upon Santa Martha, Zafra, and Llerena. On Sir
Thomas' arrival at the latter, the right wing of the covering army
rested on the heights on the south of Llerena, and the left on the
Guadiana at Don Boneto.
Lord Wellington also crossed the Guadiana on the 16th, invested
Badajoz the same evening, and broke ground before the fortress on
"St Patrick's day."
At day-break on the 18th, Sir Rowland Hill's corps crossed the
Guadiana at Merida, advanced to Almendralejo, and retraced their
steps on the 21st. In the afternoon of the 26th, we again crossed
the river, moved up its left bank to La Zarza, and next morning still
farther to Quarena. On the 28th, the cavalry, one brigade of artillery,
and the 1st brigade of infantry, advanced to Medellin and Don
Beneto. On the march the detachment was formed into two
columns, the left consisting of the 92nd regiment, and two pieces of
artillery, moved against Medellin; and the right column, commanded
by General Howard, and composed of the cavalry, 50th and 71st
regiments, one company 60th rifle corps, and remaining pieces of
artillery, against Don Beneto. Medellin was occupied about sun-set
without opposition. Informed that the enemy had retired from Don
Beneto, General Howard, on arriving close to the village, dispatched
Captain Blacier with his rifles into the town, to see that none of the
enemy lurked in it, and to obtain an interview with the chief
magistrate regarding quarters. The gallant Captain was plodding his
way through the streets, thinking on the good things of this world,
when all at once his thoughts were rivetted on the things of the
world to come. Unconscious of their contiguity to the British, a
French cavalry patrol had entered the village on a reconnoitring
excursion, and like my friend the Captain, were thinking of every
thing but what was before them. Each party was therefore moving
along in conscious security, when, on turning the corner of a street,
they unexpectedly met. With eyes looking amazement, they gazed at
each other for a few moments, and then proceeded in the usual
manner to extricate themselves from the dilemma into which false
intelligence had led both parties. A pretty little skirmish ensued, in
which the balls of the rifles made a suitable return for the favours
showered upon their heads by the Gallic sabres. After a few mortal
wounds had been given and received, the enemy, suspecting they
had got into the wrong-box, wheeled to the right-about, retired
rather precipitately, and left the gallant Captain in possession of the
well-won honours of the street.
Medellin is built along the base of a lonely hill, on the left bank of,
and close to the Guadiana. On the summit of the little conical
mount, stands a castle, better calculated to repel the assault of a
pop-gun, than a twenty-four pounder. On our arrival, we threw a
strong piquet into it, which was followed by the whole battalion two
hours before day-break next morning. On ascending the eminence,
the air was disagreeably cold, but the scene which opened to our
view at sun-rise, soon banished past miseries into the shades of
forgetfulness.
Twelve miles to the west lay before us the memorable plains and
surrounding hills of Arroyo-del-Molinos, where hundreds of Gerard's
followers breathed their farewell sigh on the 28th of October 1811.
From the ramparts of Badajoz, the continual rolling of Phillipon's
thunder, reminded us every minute that the work of mutual
destruction was proceeding with unabated violence. A few miles to
the east we had a most commanding and beautiful view of the
memorable field of Medellin, where Victor and Cuesta contended for
victory in 1810, and where, before the close of that memorable day,
victory perched on the standard of Victor, which on that fatal
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