Survey of Some Human Endocrine Glands

Endocrine organs

Central Roles of the Hypothalamus and Pituitary

Pituitary Dwarfism

Gigantism and Acromegaly

Action of Steroid Hormones

Action of Peptide Hormones

Thyroid Gland P618-623

located over trachea inferior to larynx
Hormones: Thyroid hormone Calcitonin F16.7

Hypothalamus paraventricular nucleus TRH SRIF

+
Anterior Pituitary anterior pituitary TSH

T 4, T 3

+
Thyroid

Thyroid gland

Synthesis and secretion

Thyroid follicle Thyroid follicle

Thyroid follicle

Follicle epithelial cell

EC Space

Follicle Lumen

Oxidization and organification

Thyroid peroxidase:

ITPO

Oxidation Incorporation into thyroglobulin Monoiodotyrosine Diiodotyrosine Coupling of MIT and DIT within TG to form T3 and T4 Reabsorption of TG into follicle cell Proteolysis: release of T3, T4 Secretion
Peripheral conversion of T to T 4 3 Regulated by TSH

TPO

apical membrane

Clinical uses of thyroid hormone

Levothyroxine (synthetic T4) Drug of choice for routine replacement therapy

Identical to endogenous T4 and converted to T3

Long half-life allows once daily oral administration

Liothyronine (synthetic T3)

Rapid absorption, shorter T1/2 spiking, uneven blood levels, transient action

Frequent dosing required

Use limited to situations requiring rapid response

Hyperthyroidism (thyrotoxicosis)
Characterized by: Increased cardiac output Nervousness Muscle weakness Increased BMR Hyperglycemia Hypocholesterolemia Weight loss Graves' disease: Most common form of hyperthyroidism Thyroid-stimulating immunoglobulins (TSIg) interact with the TSH receptor, activate the thyroid Symptoms: Diffuse goiter Exophthalmus - protruding eyes, mucopolysaccharide infiltration of the extraocular tissue Other signs of hyperthyroidism (above)

Hypothyroidism
Characterized by: decreased cardiac output slow mental function muscle fatigue hypoglycemia decreased body temperature Causes: Primary hypothyroidism: Hashimoto's autoimmune thyroiditis radiation damage thyroidectomy iodine deficiency autosomal defects in hormone synthesis idiopathic Secondary hypothyroidism

Hypothyroidism
Myxedema:
Onset of hypothyroidism in the adult Named for characteristic thickening of subcutaneous tissue caused by deposition of mucopolysaccharides Once thought to be due to increased mucus ("myx") formation

Cretinism:
Onset in infancy Usually due to thyroid dysgenesis Impaired physical growth Impaired brain growth and myelination Mental retardation

Adverse effects
Nervousness Hypertension Vomiting and diarrhea Increased sensitivity to heat Impaired reproductive function Cardiotoxicity Iatrogenic hyperthyroidism Especially in the elderly Arrhythmias Shortness of breath

Contraindications to T4 therapy
Use with caution in presence of: Adrenal insufficiency: increases cortisol turnover Coumarin anticoagulants: increases catabolism of clotting factors Diabetes mellitus: increases insulin requirement Stimulates gluconeogenesis and glycogenolysis Cardiovascular disease: initiate therapy slowly, monitor closely because of effects on the heart

Thionamides: Clinical uses

Graves' hyperthyroidism: 100 to 600 mg propylthiouracil/day in divided doses or 10 to 40 mg methimazole /day as single dose Reduce dose for maintenance Continue for 6 months or longer, until remission Propylthiouracil: also partially inhibits T4 T3 May be used when fast action is desired Methimazole: longer duration of action Suitable for once daily dosing Propylthiouracil indicated for hyperthyroidism during pregnancy Use minimum dose that controls symptoms

Thionamides: Clinical uses

Following radioiodine treatment: To achieve euthyroid status until effects of radiation are observed Prior to subtotal thyroidectomy: Euthyroid status improves response to surgical stress

Thionamides: Adverse effects

Skin rashes Agranulocytosis (in 0.3 % of patients) reversible upon discontinuation Arthralgia and myalgia Hepatic abnormalities necrosis (propylthiouracil) cholestatic jaundice (methimazole)

Radioactive iodine (131I)

Most common treatment in U.S. Radioactive T1/2: 8 days Rapidly and efficiently trapped by the thyroid Dose is determined by preliminary uptake test Adjusted for complete or partial destruction of thyroid with no injury to adjacent tissue Adjunctive therapy: -adrenergic blocking agents (propanolol) or Ca2+ channel antagonists (verapamil) For relief of symptoms (tachycardia, hypertension, arrhythmias) until euthyroid