Pituitary disorders Adrenal disorders Thyroid diseases

Harsinen Sanusi

ACTH

GH

PITUITARY ADENOMA

Pituitary tumors
Pituitary tumors are the most common diseases of the pituitary gland Benign and monoclonal - arise from single type of anterior pituitary cells

Variable presentation

Pituitary tumors
Hypersecretion

Function
Insufficiency

Microadenoma

Size
Macroadenoma

Classification of pituitary tumors according to size,invasiveness and expansion

Microadenomas (D < 10 mm)
Intrasellar

Macroadenomas (D > 10 mm)

Extra sellar

Non invasive

Invasive
Excessive pituitary GH-Secretion Normal pituitary GH-Secretion

Pituitary Adenomas
Commonnest causes Majority are hypersecreting

Endocrinologic abnormality

Pituitary Hypersecretion
PRL most commonly secreted by adenoma hyperprolactinemia GH Acromegaly ACTH Cushings disease

ACROMEGALY
Etiology: excessive pituitary GH secretion Sex incidence equal Mean age at diagnosis is approximately 40 years Duration of symptoms usually 5-10 years before the diagnosis established Increased late morbidity and mortality if untreated slowly progressive and spontaneous remission

Clinical manifestations of acromegaly

Manifestation of GH Excess Disturbance of other endocrine function Local manifestation

Clinical manifestations of acromegaly Manifestation of GH Excess

Acral enlargement, soft tissue overgrowth, hyperhydrosis, lethargy or fatigue, weight gain,paresthesis, joint pain, hypertrichosis, goiter, hypertension

Adults : linear growth does not occur, because of prior fusion of the epiphyses of long bones. Childhood & adoloscence Gigantism

Clinical manifestations of
acromegaly
Disturbance of other endocrine function: hyperinsulinemia, glucose intolerance, irregular or absent menses, decreased libido, hypothyroidism, galactorrhea, gynaecomastia, hyperadrenalism

Clinical manifestations of acromegaly

Local manifestations
Enlarged sella Head ache Visual deficit

Laboratory finding
GH hypersecretion > 10 ng /mL
postprandial hyperglycemia, serum insulin is increased, elevated serum phosphorus, hypercalciuria

Initial steps diagnosis :

Neuro-opthalmologic evaluation and Neuro-radiologic studies with MRI

Imaging study
Plain films: Sellar enlargement (90% cases), Enlargement of the frontal, maxillary sinuses and the jaw Thickening of the calvarium Increased thickness of the heel pad MRI

Increase in hell pad thickness

Visual Field Defects

Bitemporal hemianopsia Visual loss Large tumor diplopia, cranial nerve dysfunction (NIII,IV,VI)

Effects of pituitary tumors on the visual apparatyus

Diagnostics
Laboratory findings: GH increase 10 ng/mL (N= 1-5 ng/mL), pp plasma glucose, serum insulin, serum phosphor , hypercalciuria Imaging studies: Plain film 90% casessellar enlargement Enlargement of jaw, maxillary sinuses, increased soft tissue bulk

Treatment
Removal or destruction of pituitary tumor Reversal of GH hypersecretion Maintenance of normal pituitary function Criteria for adequate respons GH< 5 ng/mL Remission< 2 ng/mL Initial therapy transphenoidal micro surgery. Radiation th/ reserved for patients w/ inadequat responses to surgery & medical therapy

Treatment
Surgical treatment : for small or moderate size tumors (< 2cm) transphenoidal-Surgery is the treatment of choice for microadenomas (90% cure) Medical treatment: Somatostatin analog Octreotide acetate (Sandostatin) & Lanreotide (Somat uline) the therapy of choice with residual GH hypersecr. Following surgery Radiotherapy

HIPOTHALAMUS
GHRH SOMATOSTATIN

PITUITARY
DOPAMINE-AGONIST DRUGS:BROMOCRIP TINE,CABERGOLINE

GH
GH-RECEPTOR

SOMATOSTATIN AGONIST : OCTREOTIDE GH-RECEPTOR ANTAGONIST: PEGVISOMANT

IGF-1
IGF-1 :Insulin like growth factor

GH

ACTH Secreting Pituitary Adenoma (Cushing Disease)

Harvey Cushing 1932 ACTH Hypersecretion bilateral adrenal hyperplasia Spontaneous hypercorticolism(Cushing syndrome). DD: Adrenocorticosteroid excessEctopic ACTH syndrome and adrenal tumors

Clinical Features
Onset insidious, usual 20-40 y, F:M :8:1, Ectopic ACTH M:F:3:1 Central Obesity, hypertension, glucose intolerance, gonadal disfunction, moon facies, plethora osteopenia, muscle weakness, violaceous striae, hirsutism, acne,poor wound healing, fungal infection,

Diagnosis & Treatment

Basal plasma ACTH Treatment : Surgical treatment: microsurgery Radiotherapy: Conventional radiotherapy Medical therapy: no drugs supresses pituitary ACTH secretion. * Ketoconazole to inhibit adrenal steroid biosynthesis,
* Metyrapone, aminoglutethimide hypersecretion reduce cortisol

EMPTY SELLA SYNDROME

Etiology
Congenital Subarachnoid space extends into the sellaturcica with cerebrospinal fluid enlargement, remodelling (Congenital ,after pituitary surgery or radiation therapy, postpartum pituitary infarctin (sheehan syndrome)

Clinical features and Diagnosis

Midlle aged, obese women Hypertension, rhinorrhea, visual field impairment Diagnosis: MRI

CRANIOPHARYNGIOMA
Children and adolescence >80% hypothalamic-pituitary deficiencies GH deficiency most common, growth retardation, gonadotropin deficiency Symptom: intracranii pressure, decreased visual acuity Diagnose:MRI

Pituitary Insufficiency

Pituitay Insufficiency
Panhypopituitarism classic manifestation of pituitary adenomas; Hypogonadism c/ GnRH screened FSH/LH to exclude primary gonadal failure TSH or ACTH deficiency is relatively unusual

Posterior Pituitary
Antidiuretic hormon (ADH; Vasopressin)
Diabetes Insipidus : Deficient ADH action Synd Inappropriate ADH : high plasma ADH concentration

DIABETES INSIPIDUS
Is disorder of water balance caused by nonsmotic renal losses of water Etiology : deficient argenine vaasopressin (AVP=ADH) secretion (central) or end organ unresponsivenes to AVP (nephrogenic) AVP is released from cells in the posterior pituitary gland increase water permeability at the distal tubule and collecting duct of the nephron

DIABETES INSIPIDUS
Classification
Central DI; Hypophysectomy, idiopathic, familial, tumor/cyst, granuloma, autoimmune Nephrogenic DI; chronic renal disease, hypokalemia,hypercalcemia, familial, etc
DD: Primary polydipsy (Psychogenic, compulsive water drinking)

DIABETES INSIPIDUS
Symptoms:
Thirst, polyurea, daily urine volume >3 L Hypernatremia weakness,altered mentaal status, coma, seizuresSigns: Physical examination is` usually normal

Laboratory Evaluation:
Spesific gravity <1.010 Urine osmolality <300 m Osm/kg Hypernatremia

Diagnosis
HighPlasma osmolality Urine osmolality reduced Water Deprivation; Spesific-Gravity <1.005 (200mosm/Kg of water) Plasma Vasopressin low in Neurogenic DI and N/high in nephrogenic DI, low in psychogenic polydipsia ADH Radioimmunoassays

Treatment
2 goals: replace the water deficit & treat underlying abnormality Central DI
Desmopressin acetat = AVP analog DDAVP)

Nephrogenic DI
Underlying disorder should be treated if possible, diuretic, prostaglandin synthesis inhibitors, amiloride

Syndrome of inappropriate secretion of ADH (SIADH)

Etiology
Malignant lung disease, TBC, lymphoma, CNS trauma, drugs (clofibrat, chlorpropamide, HCT), HIV infection, Endocrine diseases ( adrenal insuff, myxedema)

Treatment
Fluid restriction Diuretics

Disorders of adrenocortical function

Adrenocortical hyperfunction
Glucocorticoids Aldosteronism Mineralocorticoids Virilizing tumors Androgens Feminizing tumors Estrogens
Hypopituitarism Glucocorticoids Hypoaldosteronism Mineralocorticoids Hypopituitarism Androgens Estrogens

Cushings syndrome

Adrenocortical hypofunction
Addisons disease

ADRENAL INCIDENTALOMAS
Masses found incidentally during radiographic imaging of the abdomen Incidence : 0.35-4.36% in general population In Evaluation such mass: Is the mass benign or malignant? Does the mass secrete hormones or mass disfunction

DD ADRENAL INCIDENTALOMA
Benign: Non hormone secreting (lipoma,cyst, ganglioneuroma, adenoma) Hormone secreting (pheochromocytoma, aldosteronism, subclinical Cushings syndrome Malignant Adrenocortical carcinoma metastatic neoplasm lymphoma

ADRENAL INCIDENTALOMAS
Size is important: Adrenal masses >4cm more likely malignant surgical resection should be consideration The great majority (+ 89%) are benign, non functioning masses A full biochemical workup should be completed before surgery is done

CUSHINGS SYNDROME
Chronic glucocorticoid excesssymptoms & Physical features CS Iatrogenic CS ( Chronic glucocorticoid therapy): most commonly Spontaneous CS : Pituitary (Cushing disease) Adrenal ACTH secretion non pituitary tumor (ectopic ACTH Syndrome)

CUSHINGS SYNDROME
Classification
ACTH-dependent
Pituitary adenoma (Cushing disease) 70% Nonpituitary neoplasma (ectopic ACTH)

ACTH-independent
Iatrogenic (glucocorticoid, megestrol acetat) Adrenal neoplasma (adenoma, carcinoma), Hyperplasia Factitious

Indicative of Cushing Syndrome

CUSHINGS SYNDROME
Cushings syndrome suspected Overnight 1 mg DST AM cortisol > 1.8 ug/dl AM cortisol <1.8 ug/dl Normal

24 hours urine free cortisol

Normal Elevated

Repeat if high index of suspicion

Endocrinology consultation

CUSHINGS SYNDROME
Cushings syndrome established
ACTH IRMA

<5 pg/mL CT adrenals Unilateral mass Bilateral enlargement CRH test

Peak ACTH <10pg/ml Peak ACTH >20 ug/dL IPS:P<1.8

>10 ug/mL MRI pituitary IPSS Normal Abnormal

IPS:P>2.0

Adrenal surgery

Ectopic ACTH

Pituitary Surgery

CUSHINGS SYNDROME
Treatment:
CUSHINGdisease Microsurgery, Radiation therapy, Adrenal tumors
Unilateral adrenalectomy

Ectopic ACTH syndrome Benign surgical treatment Malignant : Ketokonazole, metyrapone IATROGENIK (CUSHINGOID)
Tapering of Alternate day regimen

PSEUDO CUSHINGs SYNDROME

Obesity Chronic alcoholism Depresion

Hirsutism

Post adrenalectomy

Disorders of adrenocortical insufficiency

Deficient adrenalproduction of glucocorticoid and mineralocorticoid Adrenocortical insufficiency @ Primary adrenocortical insufficiency (Addisons disease) @ Secondary : deficient pituitary ACTH secretion, glucocorticoid therapy (most common)

Addisons Disease
Etiologi: tbc (prior 1920), Autoimmune adrenalitis adrenal atrophy (80%) Associated other immunologic and autoimmune endocrine disorders, AIDS, malignant disease Rare, female >>, 30-50 year Clinical features: weakness, fatigue, anorexia, weight loss, hyperpegmentasi, hypotension,

Addisons disease
Laboratorium :
Hiponatrimia- hiperkalemia (classic) Radiologis /CT Scan

Diagnosis
Basal adrenokortical steroid Normal Rapid ACTH stimulation test ACTH plasma

Treatment:
Replacement therapy cortisol

ACTH

Aldosterone K EBV Renin Renin substrate

Major factors regulating aldosterone secretion; EBF(Effective Blood Volume)

Angiotensin II Angiotensin I

Primary Hyperaldosteronism
Accounts for about 0.7% of cases of hypertension, Women >>, unilateral adrenocortical adenoma (Conns syndrome, 73%), 27% bilateral Hyperaldosteronism: hypertension, hypokalemia, alkalosis

Primary Hyperaldosteronism
Clinical finding: Hypertension, muscular weakness, paresthesias, headache, polydipsia, polyuria, moderate hypertension (malignant is rare) Laboratory finding: Serum potassium low, 24 hours urine collection aldosterone Imaging: CT-scan

Primary Hyperaldosteronsm
Treatment: Laparoscopic adrenalectomy, Spironolactone, antihypertensive agent Complication: Renal damage Prognosis: Improved by early diagnosis and treatment, only 2% malignant

Diseases of adrenal medulla

Pheochromocytoma
Pheochromocytomas are rare (<0,2% of hypertensive), cathecolamine-producing tumor of neurochromaffin cells. Extraadrenal Ph sympathetic ganglia are called Paraganggliomas Incidence 3-4th decades,autosomal dominat hereditary, malignant 10-15% cases Hypertension is caused by excessive plasma level epinephrine by tumor located either or both adrenals & anywhere along sympathetic nervus chain ( 90% adrenal)

Pheochromocytoma
Symptoms and Signs Usually lethal unless diagnosed and treated severe headache, perspiration, palpitation, anxiety, tremor, tachycardia Attack cyanosis, facial pallor Classical symptomatic triad: headache, sweating, palpitations Laboratory finding Urinary cathecolamines, metanephrine, creatinine, Urinary VMA

Common Symptoms in Patients with Hypertension Due to Pheochromocytoma. Symptoms during or following paroxysms Headache Sweating Forceful heartbeat with or without tachycardia Anxiety or fear of impending death Tremor Fatigue or exhaustion

Nausea and vomiting

Abdominal or chest pain Visual disturbances Dyspnea

Symptoms between paroxysms

Increased sweating Cold hands and feet Weight loss

Constipation

Pheochromocytoma
Localisation
CT scanning
Overall accuracy 90%-95% for adrenal tumours Less accurate for extra adrenal tumours

Isotope scintigraphy (MIBG scanning)

131I-MIBG stored in chromaffin granule Sensitivity 99% False negative 11% False positive 2%

Blood and Urine analysis

Plasma catecholamine levels > 1000micrograms Urinary VMA and Metanephrine levels

Pheochromocytoma
Treatment
Surgery Preoperative preparation To control hypertension & prevent CVS complications. Alpha adrenergic blockade
Phenoxybenzamine 10 mg qds 1-2 weeks before surgery Beta blockade propanolol 10 mg qds 2-3 days

Intraoperatively Phentolamine Sodium nitroprusside

Pheochromocytoma
Treatment Laparoscopic removal of the tumor treatment of choice, open laparatomy Prognosis Depends early diagnosis is made

HARSINEN SANUSI

THE THYROID GLAND

Thyroid cartilago Pyramidal lobe Left lobe Isthmus Right lobe Internal jugular vein

External carored arteri

THYROID GLAND HISTOLOGY

http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/anatomy.html

Thyroid hormone synthesis, storage and release

TRAPPING

ORGANIFICATION

PEROXIDASE H2O2

OXIDIZED IODIDE

MIT DIT T3 TGB TGB

Tyr

Tyr

Tyrosine?

COUPLING DIT DIT T4 TGB TGB

STORAGE

Iodinase
AA TGB Tyrosine

DEIODINATION RELEASE

MIT DIT

MIT

DIT

PROTEOLYSIS

TGB

T3 T4

T3 T4

Protease

T3 --TGB
T4 --TGB

CAPILLARY

FOLLICULAR CELL
Cryer PE. Diagnostic endocrinology 1976:35

COLLOID

HYPOTHALAMUS Basic elements in regulation of thyroid function TRH

T3
PORTAL SYSTEM

I
ANTERIOR PITUITARY

T4

+
TSH

FREE

T3 _

T4
TISSUE

T3

I
THYROID

+ T4

 Thyroid enlargement which may be diffuse or nodular Symptom of thyroid deficiency or Hypothyroidism Symptoms of thyroid hormon excess, or Hyperthyroidism

Usually Complain thyroid disease

Usually Complain thyroid disease

Complications of a Spesific form hyperthyroidism: Graves disease which may present which prominence of the eyes or exophthalmos and Thickening of the skin over the lower legs (rare) or thyroid dermopathy

Physical Examination
Inspection : Good light coming from behind the examiner, The patient is instructed to swallow a sip of water, Observe the gland as it moves up and down. Enlargement and nodularity can often be noted.

Physical Examination
Palpate the gland from behind the patient with the middle threes fingers on each lobe while the patients swallows. Nodules can be measured in a similar way.

Physical Examination
On physical examination the normal thyroid gland about 2cm in vertical dimension and about 1cm in horizontal dimention above the isthmus Enlarged thyroid gland is called Goiter The generalized enlargement is termed diffuse goiter, irreguler or lumpy enlargement is called nodular goiter

Diffuse goiter
Simple diffus goiter Hypertiroidism Hashimoto thyroiditis

Nodular goiter
1. Thyroid nodul 2. Thyroid cyst
3. Adenomatosa goiter 4. Subacut /chronis thyroiditis 5. Plummer thyroiditis

THYROID DISEASES
HYPERTHYROIDISM HYPOTHYROIDISM THYROIDITIS THYROID NODUL

THYROID DYSFUNCTION

PREVALENCE

Hypothyroidism Subclinical hypothyroidism Hyperthyroidism Subclinical hyperthyroidism

2% 5-7 % 0,2 % 0,1- 6,0%

 Thyrotoxicosis is the clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormone. Thyroxicosis is due to hyperactivity of the thyroid gland or hyperthyroidism Occasionally, thyrotoxicosis may be due to other causes such us excessive ingestion of the thyroid hormone or excessive thyroid hormon from ectopis site

Hyperthyroidism & Thyrotoxicosis

Conditions asscosiated with thyrotoxicosis

Diffuse toxic goiter (Graves disease) Toxic adenoma (Plummers disease) Toxic multinodular goiter Subacute thyroiditis Hyperthyroid phase of Hashimotos thyroiditis Thyrotoxicosis factitia Rare: Ovarian struma, metastatic thyroid carcinoma, hydatiform mole,

GRAVES DISEASE (DIFFUSE TOXIC GOITER)

GD is the most common form of thyrotoxicosis, may occur at any age, more commonly in females than in males (5X) The syndrome consist one or more of the following features: 1. THYROTOXICOSIS 2. GOITER 3.OPHTHALMOPATHY(Exophthalmos) 4. DERMOPATHY (Pretibial myxedema)

ETIOLOGY & PATHOGENESIS

GD is currently viewed as an autoimmun disease of unknown cause Ther is a strong familial predisposition in that about 15%. 50% GD have circulating thyroid autoantibodies Peak incidence 20-40-year T-lymphocytes sensitized to antigen within thyroid gland and stimulate B lymphocyte antibodies

Clinical features Gravess disease

Symptoms: in younger patients: palpitation, nervousness, easy fatigability, hyperkinesia, diarhhea, excessive sweating, intolerance to heat, weight loss, without loss appetite Signs: Thyroid enlargement, exophthalmos, tachycardia, muscle weakness, tremor Older patients cardiovascular & myopatic predominate clinical manifestation palpitatation, dyspnea on exersice, tremor, nervousness, weight loss

Ophtalmopathy Graves disease

Infiltrative sympathetic overstimulation
Lid retraction (Dalrymphes sign) Van Graves sign late palpebra sup Stellwats sign the wink eyes late Jefroys sign fold of forehead not see Mobiussign convergention of the eyes late

Infiltratif autoimmune
Exophthalmus, oculopathy congestif: cheimosis, conjunctivitis, periorbital edema Ulcerasi Cornea , neuritis optica, atrophi n opticus

The Eye signs of GravesDisease (ATA )

Class 0 1 2 3 4 5 6

Definition

No signs no symptoms Only signs, no symptoms, (signs limited to upper lid retraction, stare,lid lag) Soft tissue involvement (symptom & signs) Proptosis (measured with Hertel exophthalmometer) Extraocular muscle involvement Corneal involvement Sight loss (optic nerve involvement)

DISEASE SEVERITY
Thyroid eye disease can be divided into

MILD disease MODERATE disease SEVERE disease

MILD DISEASE
Usually young patient Dry eyes---->lubricants Lid retraction Lid malposition-entropion Mild proptosis

MODERATE DISEASE

Thyroid myopathy asymmetric involvement tends to involve vertical muscles in Asians

LID RETRACTION

HERTEL EXOPHTHALMOMETER
EXOPHTHALMOS : >18 MM

Computerised Axial Tomography

Thyroid Dermopathy
Thickening of the skin,over the lower tibia due to accumulation glycosaminoglicans , rare (2-3%) TSH-R Ab high titer Osteopathy in the metacarpal bones

Non Pitting oedema

Suspected hyperthyroidism TSH &FT4 Low TSH & Normal FT4 Measure FT3
TSH- secreting pituitary adenoma. Low TSH & high FT4 Normal / high TSH & high FT4

Normal FT4 &TSH

Hyperthyroidism excluded

Normal FT3 Subclinical hyperthyroidism Evolving Graves disease Or toxic nodular goiter Excess thyroxine replacement Non thyroidal illness

High FT3

Hyperthyroidism

Thyroid hormoneresistance syndrome

T3 Hyperthyroidism

Repeat tests in 2-3 months: annual follow-up if no progression

Laboratoy tests useful in DD of hyperthyroidism

Gravesdisease Toxic nodular goiter Thyroiditis Gestational Hyperthyroidism Factitious or iatrogenic hyperthyroidism Thyroid Carcinoma Struma Ovarii Tumor secreting Chorionic gonadotropin Familial nonautoimmun hyperthyroidism

Atypical fashion Graves Disease

Thyrotoxic periodic paralysis: usually Asian males, sudden attack flacid paralysis, hypokalemia, usualy subsides spontaneously. Prevention: K+ supplement & Betablockers Thyrocardiac disease: primarily with symptoms of heart involvement: refrsctory AF insensitif digoxin or high output heart failure, no evidence underlying heart disease (50%). Treatment of thyrotoxicosis cure

Atypical fashion Graves Disease

Apethetic hyperthyroidism:

Older patients: weight loss, small goiter, slow AF, severe depression with none clinical features

Treatment of Graves Disease

1. Antithyroid drug therapy: Young pts, small glands, mild disease Propylthiouracil, methimazole (6m-15 y), relaps 50-60%. PTU inhibits the conversion T4T3, effect more quickly compare Methimazole : longer duration of action, Single dose Therapy 3-6 months tapering dose and combination levothyroxin 0.1 mg/d 12-24 months Allergic reaction (rash, agranulocytosis)

Treatment of Graves diseae

Surgical treatment Surgical subtotal thyroidectomy treatment of choice for very large glands, or multinodular goiter, prepared wth anti thyroid drug (about 6 months) Complication:Hypothyroidism,recurent laryngeal nerve injury

Treatment of Graves disease

Radioactive iodine therapy USA NaI 131I euthyroid over 612 weeks, Complication hypothyroidism

Treatment of Graves disease

Other medical measures: Beta-adrenergic blocking agents Propranolol 10-40 mg every 6 hours, multivitamin supplements, phenobarbital as sedative + to lower T4 levels Cholestyramine, 4 gr orally 3X daily lower T4

Complication of Graves Disease

Thyrotoxic crisis (thyroid storm)
Acute exacerbation symptoms thyrotoxicosis. May be mild & febrile until life threatning. Etiology : after thyroid surgery in patients who has been inadequatlely prepared. RAI131, parturition in adequately controlled thyrotoxicosis or stressfull illnes.

Complication
Thyrotoxic crisis(thyroid storm):
Clinical manifestation:Fever,Sweating, flushing, tachycardia/AF, heart failure, agitation,delirium, coma, jaundice, nausea vomiting and diarhea. Treatment: Propranolol 1-2 mg IV, PTU 250 mg every 6 hours. Hydrocortison, supportive therapy

 Clinical manifestation marked hypermetabolism, excessive adrenergic response, fever, flushing, sweating, tachicardia, AF, heart failure, delirium , coma, GI Symptoms

HYPOTHYROIDISM

HYPOTHYROIDISM
Etiology
Primary:Hashimoto thyroiditis, Radio
active iodine therapy for Graves disease, Subtotal thyroidectomy, Excesive iodide intake, subacute thyyroiditis, Iodide deficiency

Secondary :
Hypopituitarism due to pituitary adenoma

Tertiary :
Hypothalamic disfunction (rare)

HYPOTIROIDISM
Clinical finding
Incidence : Various causes depending geographic & enviromental factors Hashimoto thyroiditis the most common cause of hyperthyroidism Newborn infants (Cretinism) Fatigue, coldness, weight gain, constipation, menstrual irregularities, muscle cramps

HYPOTIROIDISM
Physical findings: Cool,rough, dry skin, puffy face and hands, ahoarse voice, slow reflexes Cardiovascular sign: bradycardia, diminished CO, low voltage QRS, cardiac enlargement Pulmonary function: Respiratory failure Intestinal paralysis slowed , chronic constipation, ileus Renal function. Decresed GFR, renal impairement Anemia, Severe muscle cramp, parestesias, muscle weaknes CNS symptoms: fatigue, inability to concentrate

Pituitary- thyroid relationships in primary hypothyroidism TRH

Dopamine

Hypothalamus
Somatostatin

TSH

Pituitary

Tissues T3, T4

THYROID

Complication
Myxedema coma end stage of untreated hypothyroidism, Cause Radiotherapy in Graves Disease Myxedema & Heart disease CAD Hypothyroidism Neuropsychiatric disease depression, confuse, paranoid, manic

Treatment Hypothyroidism
Levothyroxine (T4), not liothyronine (T3) because rapid absorption, short half life, transient effect. Dosis T4, 1X in the morning to avoid insomnia 0.05 mg-0.2 mg/d Mixedema coma ICU, intubation & mechanical ventilation, Treat infection, heart failure, IV drips with caution, levothyroxin IV

EXAMPLES OF THYROID DISEASES

1 Hypothyroidism

Hyperthyroidism
www.hsc.missouri.edu/~daveg/thyroid/thy_dis.html

Complication
Myxedema coma end stage of untreated hypothyroidism, Cause Radiotherapy in Graves Disease Myxedema & Heart disease CAD Hypothyroidism Neuropsychiatric disease depression, confuse, paranoid, manic

Definition
Thyroiditis heterogenous group of inflamatory disorders the thyroid gland Etiologies range from autoimmune to infectious origins Clinical course Acute, subacute, or chronic. Can be euthyroid, transient phase thyrotoxicosis and / or hypothyroidism. Painless or painfull

Classification of thyroiditis
I. Autoimmune thyroiditis Chronic autoimune thyroiditis
Hashimotos thyroiditis Atrophic thyroiditis Focal thyroiditis Juvenile thyroiditis

Silent thyroiditis / Postpartum thyroiditis II. Subacute thyroiditis

III. Acute suppurative thyroiditis IV. Riedels thyroiditis

Classification of thyroiditis
Hystologic classification
Chronic lymphocytic

Synonims
Chronic lymphocytic thyroiditis, Hashimotos thyroiditis Subacut lymphocytic thyroiditis, Postpartum thyroiditis, Sporadic painless thyroiditis Subacut granulomatous thyroiditis De Quervains thyroiditis Suppurative thyroiditis Acut thyroiditis Riedels struma Riedels thyroiditis

Subacute lymphocytic Granulomatous

Microbial inflamatory Invasive fibrosis

Terminology for Thyroiditis.

Type Hashimotos thyroiditis thyroiditis goiter Painlesspostpartum thyroiditis Painless sporadic thyroiditis Painful subacute thyroiditis Synonim Chronic lymphocytic thyroiditis Chronic autoimmune Lymphadenoid Postpartum thyroiditis Subacute lymphocytic thyroiditis Silent sporadic thyroiditis Subacute lymphocytic thyroiditis Subacute thyroiditis de Quervains thyroiditis Giant-cell thyroiditis Subacute granulomatous thyroiditis Pseudogranulomatous thyroiditis

Terminology for Thyroiditis.

Type Suppurative thyroiditis Synonim Infectious thyroiditis Acute suppurative thyroiditis Pyogenic thyroiditis Bacterial thyroiditis -

Drug-induced thyroiditis (amiodarone, lithium, interferon alfa, interleukin-2) Riedels thyroiditis

Fibrous thyroiditis

Hashimotos thyroiditis (Chronic thyroiditis)

Hakaru Hashimoto (1912) 4 patients chronic disorder of the thyroid diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and eosinophilic change in some acinar cells

Dr Hakaru Hashimoto

Hashimotos thyroiditis Hashimoto thyroiditis is the most common cause of hypothyroidism & goiter in the United States
Statosky J et al. Am Acad of Family physicians 2000;61:1054

Hashimotos thyroiditis
Etiology & pathogenesis HT is immunologic disorder which lymphocytes become sensitized to thyroidal antigens and auto antibodies are performed. Thyroid antibodies in HT are: 1.Thyroglobulin antibody (Tg Ab) 2. Thyroid peroxidase antibody (TPO Ab) = Microsomal antibody) 3. TSH Receptor blocking antibody (TSHR Ab block)

Clinical Manifestation Hashimotos Thyroiditis

Symptom & Signs
HT usually presents with goiter , euthyroid or mild hypothyroidism. Sex distribution : F/M 4:1 Painless & patients may be anware of the goiter

Laboratory findings
T4 N/ low, TSH will be elevated. RAIU may be high, normal or low Tg Ab & TPO Ab positif Fine needle aspiration biopsy large infiltration lymphocytes Hurttle cells

Diagnostic procedures
Test of thyroid autoimmunity: TPOAb 95% + in Hashimoto thyroiditis & 90% Atrophic thyroiditis TgAb less frequently + Diagnostic specificity of thyroid antibody tests is not absolute. Test for thyroid function TSH, fT4 RAIU: normal, low or high. USG:diffusely reduced echogenecity. FNAB not necessary,excep. rapidly enlarging goiter

Diagnosis of Hashimotos thyroiditis

Diffuse goiter
Anti microsomal (or TPO) antibody Anti-thyroglobulin antibody

Positive

Sign symptom of hypothyroidism

Negative

Hashimotos thyroiditis

US Biopsy
*Simple goiter,
adenomatous goiter etc

Positive

Negative

Other diseases*

Treatment Hashimotos thyroiditis

Treatment
Goiter small & asymptomatic not require therapy Levo-thyroxine is given over hypothyroidism to supress TSH & decreased serum thyroid antibody. Levo-thyroxine in euthyroid, still controversial

Treatment
Corticosteroids : regression pain, reduction in size of the goiter, thyroid antibody, not recommended in benign disease.

Surgery indicated pain, cosmetic, or pressure symptoms after levothyroxine and corticosteroid therapy.

Riedels thyroiditis
Rare 1,06/100.000, middle age or elderly women Etiology unknown (autoimmune process or primary fibrotic disorder) Characterized fibrosis replaces normal thyroid parenchyma,1/3 cases multifocal fibrosclerosis

Riedels thyroiditis
Thyroid fibrosis (stony hard,woody), painless, progressive anterior neck mass, Generalized fibrosing (1/3 patients), pressure symptoms laryngeal nerve paralysis or hypoparathyroidism (rare) Usually euthyroidism, hypothyroidism (30%) Laboratorium : non spesific USG/CT-Scan inconclusive Difinitive diagnosis open Biopsy

Riedels thyroiditis
Treatment: Corticosteroids medical treatment of choice Tamoxipen, methotrexate inhibitor fibroblast proliferation ( early stages) Levothyroxine hypothyroidism Surgical care diagnosis, relieving tracheal compression Mortality asphyxia (6-10%), extrathyroidal fibrotic lesions may complicate the prognosis

Subacute thyroiditis
Cause unknown ( viral infection (?) preceded URT infection, coincidence viral disease (mumps, measles, Echo virus, adeno virus, epst. Barr virus, influenza) Women : Men (3-5:1) Onset: 20-60 yr Summer

Subacute thyroiditis
Palpation thyroid: enlarged, asymetrical, nodul, firm, tender & painful. Thyrotoxicosis during inflamatory phase euthyroidism hypothyroidism euthyroidism (4th phases) Laboratorium: ESR increase, leukocyt N/ increase, fT4,,TSH, RAIU Recovery 4-6 months, spontaneous

remitting

Changes in serum T4 & Radiactive iodine uptake in patients with subacute Thyroiditis
T4 ug/dL

24-hour 131 I uptake %

20

T4

40

15 10

30

20

5
I Eu 4 Hypo 11 Eu -

10
131

0 Phase : Weeks:

0
Woolf PD, Daly R :Am J Med 197;60:73

Hyper 1

Laboratory findings during different phases of subacute thyroiditis

Phase

T4 &/T3 Level

TSH level
Low

RAIU value
<5%

Thyrotoxicosis

High

Hypothyroid
Recovery

Low
Normal

Normal,or high
High to normal

Normal to high
High to normal

Treatment Subacute thyroiditis

Symptomatic: Acetaminophen 4X 0,5g, NSAID or glucocorticoid (prednison 3 X 20 mg (7-10 days) Betablockers symptoms of thyrotoxicosis L-thyroxine 0.1-0.15 mg /daily hypothyroid phase. Long-term L-thyroxine permanent hypothyroidism (10%)
Antibioticsno value

Thyroidectomy rarely

Clinical Differentiating of the Subtype Thyroiditis NECK PAIN

YES

N0

RAIU
INCREASED DECREASED

PRESENTING SYMPTOMS
HYPERTHYROIDISM
HYPOTHYROIDISM

MICROBIAL INFLAMMATORY THYROIDITIS

SUBACUTE GRANULOMATOUS THYROIDITIS

RAIU

CHRONIC LYMPHOCYTIC THYROIDITIS

GRAVES DISEASE

SUBACUT LYMPHOCYTIC THYROIDITIS

Statosky J et al. Am Acad of Family physicians 2000;61:1054

Acute suppurative thyroiditis

Rare, serious, bacterial inflamatory disease, children, 20-40 yr, sex ratio 1:1 Etiologi: Infectious: Staph. aureus, strep.pyogenes, strep. pneumonia, esch.coli, pseudomonas aeruginosa Infection by hematogenous, direct trauma

Symptoms & signs

Neck pain, warm, tenderness, the neck unable to extend Dysphagia, dysphonia, referred to ear, mandibula, lymphadenopathy Systemic manifestation: fever, chills, tachycardia, malaise Palpation: unilateral, erythematous

Acute suppurative thyroiditis

Thyroid function : Euthyroidism Laboratorium :TPO antibodies absent, ESR high, PMN leukocytosis 24-hour 123I uptake normal FNA Biopsy: purulent material

Treatment: antibiotics or surgical drainage

Chronic-pyogenic thyroiditis
Etiology : Salmonella typhosa, syphilis, tuberculosis,echinococcus, actinomyces Symptoms: Suppurative, non suppurative Treatment: antibiotic, drainage

Thyroid nodules & Thyroid cancer

Thyroid nodules - prevalence

Thyroid nodules common, increase with age 30-60% of thyroids have nodules at autopsy Palpation: 5-20% (>1cm) U/S: 15-50% (>2mm)

Diagnostic approach
Fine Needle Aspiration (FNA)
10-20% risk of suspicious cytology, therefore thyroid surgery 95% of histology will be benign, and surgery unnecessary

Isotop Scann(CT)
rarely used for evaluation 80% of nodules are cold small cold nodules may be missed hot nodules may be malignant

Ultrasonography (USG)

Diagnostic approach - ultrasound

Identifies solid v. cystic nodules Identifies MNG May aid FNA Does not exclude malignancy

Diagnostic approach - other tests

Calcitonin very high results diagnostic for MTC risk of borderline false positives not for routine use Thyroglobulin not helpful for exclusion of carcinoma: overlap with benign disease best for follow-up after thyroidectomy

Thyroid nodules & Thyroid cancer

In 95% of cases , thyroid cancer presents as a nodule or lump in the thyroid nodul thyroid. Thyroid nodule extremely common, particularly women.Prevelance in USA 4% in adult population. F:M ratio 4:1. Thyroid cancer rare. Incidence 0.004% per year

Diffrentiation benign & Malignant lesions

History : Family history of goiter suggests benign disease, endemic goiter Physical characteristics: Benign: older age, woman, soft nodule, multi nodular goiter. Malignant: Children, young, male, solitary, firm nodule, vocal cord paralysis, firm lymph nodes, distant metastasis

Malignant thyroid Carcinoma

Papillary Carcinoma Folliculare Carcinoma Medullary Carcinoma Anaplastic Carcinoma Lymphoma 75 % 16 % 5% 3% 5 -10 %

Management of the solitary nodule

True solitary nodule?
No Yes

FNAC

Benign

Malignant

Indeterminate

Follicular

Watch?

Surgery

Repeat FNAC

Surgery

Indeterminate

Surgery

Treatment
Thyroidectomi Jodium 131Radioactive Thyroxine supression

FNA POSITIF MALIGNANCY Differenteated Under 2cm, no invasion Lobectomy and isthmusectomy Levothyroxine for life Over 2cm, or multicentric, or invasive Near total thyroidectomy and modified neck dissection Liothyronine, 75-100 mcg/d for 3 mos, discontinue 2 week. Low iodine diet Scan with 2-5 mCi 131 I Negatitive scan Levothyroxine for life No recurence cure Recurrence + - Scan Local removal to prevent obstruction (palliative therapy) X-ray therapy or chemotherapy (or both) plus levothyroxine replacement therapy Undifferenteated

Repeat after 12 months

Positive scan 50-150 mCi131 I (therapeutic dose)

X Ray therapy or chemo therapy (or both)

Treatment of thyroid cancer

Papillary cancer
< 1.5 cms > 1.5 cms Lobectomy & isthmusectomy Total thyroidectomy Total thyroidectomy

Follicular cancer
Hurthle Medullary

Total thyroidectomy Total thyroidectomy & central neck dissection