ENDOCRINE DISORDERS

PREPARED by Mrs.C. Bascombe-Mc Cave

FUNCTIONS
• To regulate and integrate body functions via the release of
chemical substances /hormones into the bloodstream
• The Master Gland
• The pituitary gland

• Primary function is to control other glands.

• Produces many hormones.
• Secretion is controlled by the hypothalamus in the base of
the brain.
 Categories of Disturbances of Endocrine Function
• Hypofunction: underproduction of hormone
• Causes
• Congenital defects
• Disruption in blood flow, infection, inflammation,
autoimmune responses, or neoplastic growth
• Decline in function with aging
• Atrophy as the result of drug therapy or unknown reasons
• Receptor defects
Categories of Disturbances of Endocrine Function (cont.)
• Hyperfunction: excessive hormone production
• Causes
• Excessive stimulation and hyperplasia of the
endocrine gland
• Hormone-producing tumor of the gland
• Administration of exogenous hormones eg
glucocorticoids to suppress the inflammatory
response may lead to Cushing’s syndrome
 Categories of Endocrine Disorders
• Primary disorders
• Originate in the target gland responsible for producing the
hormone
• Secondary disorders
• The target gland is essentially normal, but its function is altered by
defective levels of stimulating hormones or releasing factors from
the pituitary system
• Tertiary disorders
• Result from hypothalamic dysfunction
• Both the pituitary and target organ are understimulated
 THYROID DISORDERS
Thyroid gland
• lies in the anterior neck just below the larynx.
• secretes hormones- thyroxine(T4 ) and
triiodthyronine (T3 ) and
• calcitonin secreted by the parathyroid glands
• Uses iodide to form thyroid hormones
• TH are bound to thyroxine-binding globulin (TBG) and
other plasma proteins for transport
 Three Major Thyroid-Binding Proteins
• Thyroid hormone–binding globulin (TBG)
• Carries approximately 70% of T4 and T3
• Thyroxine-binding prealbumin (TBPA)
• Binds approximately 10% of circulating T4 and lesser
amounts of T3
• Albumin
• Binds approximately 15% of circulating T4 and T3
Major Functions of Thyroid Hormone

• Regulates metabolism and protein

synthesis
• Influence growth and development in
children
• Mental development and attainment
of sexual maturity
 ALTERATIONS OF THYROID FUNCTION
Overactivity (Too much hormone)
-Increased metabolic rate
-Increased food intake but loss of weight
-Hyperthyroidism (Grave’s disease)
-Goitre (swollen neck, maybe bulging eyes)
 ALTERATIONS OF THYROID FUNCTION
Underactivity (Not enough hormone)
- Hypothyroidism (Hashimoto’s disease)
- Reduced metabolic rate
- Low food intake but gain of weight
- Myxoedema (when onset in adults)
- Cretinism (when onset in children)
- Can also cause a goitre
- Elevated serum cholesterol
 GOITER
• An enlargement of the thyroid gland
• Caused by inflammation/neoplasm
Adenoma ( Benign)
Carcinoma ( malignant-papillary,follicular,medullary or anaplastic)
• Can be toxic or non toxic
• Non toxic is most common among females
• Toxic occurs from long standing non-toxic goiter. More common in the
elderly
• Can be classified as endemic (caused by lack of iodine in diet) or
• sporadic (caused by ingestion of large amounts of goitrogenic foods or
use of goitrogenic drugs)
 GOITER (Cont’d)
• Goitrogenic food and drugs contain agents that
decrease T4 production

• Goitrogenic foods
Cabbage, soybeans, peanuts ,peaches, peas,
strawberries, spinach

• Goitrogenic drugs
Propylthiouracil, iodides,cobalt, lithium
 GOITER (cont’d)
PATHOPHYS
• Occurs when TG is unable to secrete TH to meet
metabolic needs
• May be as a result of impaired hormone production
or lack of iodine
• TG increases to compensate
 MANIFESTATIONS
• Single or multinodular, firm, irregular enlargement of TG
• Asymptomatic
• Respiratory distress-compression of trachea
• Stridor
• Dysphagia –compression of trachea
• Dizziness/syncope when arms are raised above head- obstructed
venous return
• Symptoms of hyperthyroidism
Measures Used to Diagnose Thyroid
Disorders
• Measures of T3, T4, and TSH
• Resin uptake test
• Assessment of thyroid autoantibodies
• Radioactive iodine uptake test
• Thyroid scans
• Ultrasonography
• CT and MRI scans
• Fine-needle aspiration (FNA) biopsy of a thyroid nodule
TREATMENT
• Hormone replacement –thyroxine
and Lugol’s iodine)
• Diet
• Radiation
• Surgery
Pancreas
• a key gland located in the folds of the duodenum
has both endocrine and exocrine functions
secretes several key digestive enzymes
 Tissue Types and Functions of the Pancreas
• The acini
• Secrete digestive juices into the duodenum
• The islets of Langerhans
• Secrete hormones into the blood
• Composed of beta cells that secrete insulin, alpha cells
that secrete glucagon, and delta cells that secrete
somatostatin
Islets of Langerhans
• specialized tissues in which the endocrine
functions of the pancreas occurs
• include 3 types of cells:
• alpha ( )
• beta ()
• delta ()
• each secretes an important hormone.
 Alpha () cells
• release glucagon, essential for controlling blood
glucose levels.
• When blood glucose levels fall,  cells  the
amount of glucagon in the blood
• The surge of glucagon stimulates the liver to
release glucose stores (from glycogen and
additional storage sites).
• Also, glucagon stimulates the liver to manufacture
glucose –glucogenesis
 Beta Cells ()
• release insulin (antagonistic to glucagon).
• Insulin  the rate at which various body cells take up
glucose.
• Thus, insulin lowers the blood glucose level.
• Insulin is rapidly broken down by the liver and must
be secreted constantly.
Delta Cells ()

•produce somatostatin, which inhibits both

glucagon and insulin.
Actions of insulin and Glucagon on Glucose
• Insulin
• Increases glucose transport into skeletal muscle and
adipose tissue
• Increases glycogen synthesis
• Decreases gluconeogenesis
• Glucagon
• Promotes glycogen breakdown
• Increases gluconeogenesis
 Actions of insulin on Protein
• Increases active transport of amino acids into
cells
• Increases protein synthesis by increasing
transcription of messenger RNA and accelerating
protein synthesis by ribosomal RNA
• Decrease protein breakdown by enhancing the
use of glucose and fatty acids as fuel
 Actions of Glucagon on Proteins

•Increases transport of amino acids into

hepatic cells
•Increases breakdown of proteins into amino
acids for use in gluconeogenesis
•Increases conversion of amino acids into
glucose precursors
Other Hormones Affecting Blood
Glucose
• Catecholamines
• Epinephrine and norepinephrine
• Help to maintain blood glucose levels during periods of stress
• Growth hormone
• Increases protein synthesis in all cells of the body, mobilizes fatty acids
from adipose tissue, and antagonizes the effects of insulin
• Glucocorticoids
• Critical to survival during periods of fasting and starvation
• Stimulate gluconeogenesis by the liver
 Diabetes Mellitus
• Disorder of carbohydrate, protein, and fat metabolism
• Results from an imbalance between insulin availability and
insulin need
• Can represent:
• An absolute insulin deficiency
• Impaired release of insulin by the pancreatic beta cells
• Inadequate or defective insulin receptors
• Production of inactive insulin or insulin that is destroyed
before it can carry out its action
 Types of Diabetes
• Type 1 results from:
• Loss of beta cell function
• An absolute insulin deficiency
• Type 2 results from:
• Impaired ability of the tissues to use insulin
• A relative lack of insulin or impaired release of insulin in
relation to blood glucose levels
 Subdivisions of Type 1 Diabetes
• Type 1A
• Immune-mediated diabetes
• Type 1B
• Idiopathic diabetes
Factors Involved in the Development of Type 1A
Diabetes
• Genetic predisposition (diabetogenic genes)
• A hypothetical triggering event that involves an environmental
agent that incites an immune response
• Immunologically mediated beta cell destruction
 Idiopathic Type 1B Diabetes
• Those cases of beta cell destruction in which no evidence of
autoimmunity is present
• Only a small number of people with type 1 diabetes fall into
this category; most are of African or Asian descent
• Type 1B diabetes is strongly inherited
• People with the disorder have episodic ketoacidosis due to
varying degrees of insulin deficiency with periods of absolute
insulin deficiency that may come and go
Metabolic Abnormalities Contributing to Hyperglycemia in Type 2
Diabetes

• Impaired beta cell function and insulin

secretion
• Peripheral insulin resistance
• Increased hepatic glucose production
 Causes of Beta Cell Dysfunction in Patients with
Diabetes
• An initial decrease in the beta cell mass
• Increased beta cell apoptosis/decreased regeneration
• Long-standing insulin resistance leading to beta cell exhaustion
• Chronic hyperglycemia can induce beta cell desensitization
(‘glucotoxicity’)
• Chronic elevation of free fatty acids can cause toxicity to beta
cells (‘lipotoxicity’)
• Amyloid deposition in the beta cell can cause dysfunction
 The Three Poly’s of Diabetes

• Polyuria
• Excessive urination
• Polydipsia
• Excessive thirst
• Polyphagia
• Excessive hunger
Other Symptoms of Hyperglycemia

• Weight loss
• Recurrent blurred vision
• Fatigue
• Paresthesias
• Skin infections
Blood Tests
• Fasting Blood Glucose Test (FBS)
• Random Blood Glucose Test (RBS)
• Glucose tolerance test (GTT)
• Capillary Blood Tests and Self-Monitoring of
Capillary Blood Glucose Levels
• Glycated Hemoglobin Testing
 Treatment Plans for Diabetes
• Nutrition therapy
• Exercise
• Anti-diabetic agents
 Oral Anti-diabetic Agents
• Sulfonylureas eg. Daonil, diabinese
• Repaglinide and nateglinide
• Biguanides eg metformin/glucophage
• α-Glucosidase Inhibitors (prevent digestion of
CHOs)
• Thiazolidinediones
 Three Principal Types of Insulin
• Short-acting
• Intermediate-acting
• Long-acting
 Acute Complications of Diabetes
• Diabetic ketoacidosis
• Hyperosmolar hyperglycemic state
• Hypoglycemia
 Major Metabolic Derangements in DKA

• Hyperglycemia
• Ketosis
• Metabolic acidosis
 Definitive Diagnosis of DKA
• Hyperglycemia (blood glucose levels >250 mg/dL)
• Low bicarbonate (<15 mEq/L)
• Low pH (<7.3)
• Ketonemia (positive at 1: 2 dilution)
• Moderate ketonuria
Characteristics of Hyperosmolar Hyperglycemic
State (HHS)
• Hyperglycemia (blood glucose >600
mg/dL)
• Hyperosmolarity (plasma osmolarity >310
mOsm/L)
• Dehydration
• The absence of ketoacidosis
• Depression of the sensorium
Factors Contributing to Hyperglycemia

• Increased resistance to the effects of

insulin
• Excessive carbohydrate intake
 Factors Precipitating an Insulin Reaction in
Type 1 Diabetes
• Error in insulin dose
• Failure to eat
• Increased exercise
• Decreased insulin need after removal of a stress
situation
• Medication changes
• Change in insulin site
• Alcohol
Chronic Complications of Diabetes
• Disorders of the microvasculature
• Neuropathies, nephropathies, and
retinopathies
• Macrovascular complications
• Foot ulcers
• Infection –UTI, Candida, Dental caries
 Chronic Complications of Diabetes (cont’d)
• Result from elevated blood glucose levels and associated
impairment of lipid and other metabolic pathway
• Diabetic neuropathy-leading cause of ESRD
• Diabetic retinopathy-leading cause of blindness
• Diabetic peripheral neuropathies-affect both somatic and
autonomic nervous systems-Major contributor to lower
extremity amputations
• Macrovascular disorders-CHD,stroke,PVD
Pathologic Changes Observed with Diabetic
Peripheral Neuropathies
• Thickening of the walls of the nutrient
vessels that supply the nerve
• Leading to the assumption that vessel
ischemia plays a major role in the
development of neural changes
• Segmental demyelinization process that
affects the Schwann cell
• Accompanied by a slowing of nerve
conduction
Classification of Diabetic Peripheral Neuropathies
• Somatic
• Polyneuropathies (bilateral sensory)
• Mononeuropathies
• Amyotrophy
• Autonomic
• Impaired vasomotor function
• Impaired gastrointestinal function
• Impaired genitourinary function
• Cranial nerve involvement