Thyroid gland The name "thyroid" comes from the Greek word which means "shield"
Thyroid gland , the largest single endocrine gland (20-25 g), is
located just below the level of the larynx
It has two lobes joined by a central isthmus at tracheal rings 2, 3, 4
Blood flow is ~ 5mL/min from superior and inferior thyroid arteries
Composed of numerous spherical follicles with outer layer of cuboidal
epithelium and filled with proteinous colloid ( proteinaceous depot of thyroid
hormone precursor )
A few C cells ( parafollicular cells ) are seen in the walls of the
follicles that produce calcitonin , a hypocalcemic hormone
About 80 μg/day of iodine is utilized for thyroid hormone synthesis
Activity of the gland is regulated by TRH-TSH axis
TRH ( a tripeptide ) thyrotrops
TSH T 4 , T 3
T 4 , T 3 TSH receptors on thyroid gland
T 4 , T 3
TSH stimulates all steps of thyroid hormones synthesis
TSH binds with membrane receptors adenylate cyclase
c-AMP protein kinases effects
T 4 , T 3 TSH secretion
Circulating T 4 & T 3 act directly on the anterior pituitary (negative
Hypothalamus receives input and sends a
signal to the Anterior Pituitary via TRH
Thyrotrophin Releasing Hormone .
TRH stimulates the Anterior Pituitary to
release TSH .
Thyrotrophin which travels in the blood to
the Thyroid Gland.
Thyrotrophin increases I- uptake and
stimulates production of M.I.T., D.I.T. And
hence production of T 3 and T 4 .
Somatostatin released by the Hypothalamus
inhibits TRH release .
Protirelin is a synthetic compound that mimics TRH.
Thyrotrophin There is negative feedback between Thyrotrophin and T 4 secreted by the Thyroid gland. Thyrotrophin stimulates follicle cell receptors, which leads to:
increased uptake of I- (main mechanism of action)
stimulates cAMP production inside the follicle cells
increases synthesis of thyroglobulin
leads to generation of H 2 O 2 for the iodination of iodine
Plasma Iodide Concentration
This has a pronounced effect on Thyroid function.
Daily intake of Iodide (70mg) is required to maintain T 4 production.
Decreased Iodide in the diet causes decreased hormone production and stimulates
Very slow response (weeks) to changed Iodide levels in the blood.
C an take a long time for imbalances to manifest in symptoms .
Iodine trapping and organification:
extracellular iodide is trapped into follicular cells oxidesed (peroxidase in
presence of H 2 O 2 ) iodine + tyrosine molecule in thyroglobulin
MIT & DIT
Coupling (peroxidase enzyme):
MIT + DIT T 3 ( triiodothyronine )
2 DIT T 4 ( thyroxine )
T 3 & T 4 remain stored in the colloid
T4, T3, MIT, DIT on thyroglobulin endocytosis lysosomes
(stimulated by TSH) proteolysis of the thyroglobulin molecule T 4 , T 3
- MIT & DIT are deiodinized iodine is reused for thyroid hormone synthesis
Steps of thyroid hormone synthesis Iodine trapping (using iodide pump); thyroglobulin synthesis; oxidation of iodide to iodine; iodination of tyrosine molecules within the thyroglobulin molecule to give MIT and DIT at the apical border of the cell; coupling of MIT and DIT to give T3 and T4 still within the thyroglobulin molecule in the colloid; pinocytosis of thyroglobulin and proteolysis of thyroglobulin and release of T3 and T4
Transport of Thyroid Hormones Once T 3 and T 4 are released into the blood they are bound to a serum protein, thyroxine-binding globulin (TBG) , albumin and prealbumin Only free (unbound) hormone is metabolically active Total hormone level increases when TBG increases (in pregnancy or with oral contraceptive treatment) Concentrations of T 3 and T 4 are quite different in blood and inside cells: T 3
Small pool in the body
Mostly found inside tissue cells
Fast turnover rate in the body
Large pool in the body
Mostly found in the blood
Slow turnover rate in the body
T 4 is often regarded as a prohormone as it is converted to T 3 once inside cells.
Effects of thyroid hormones
T 3 /T 4 enter the target cell cytoplasm T 3 binds to nuclear receptors
messenger RNA protein synthesis effects on cellular function
oxygen consumption (exception – brain, testes, pituitary) & heat production
basal metabolic rate (BMR)
cellular & gastrointestinal absorption of glucose, glycolisis & gluconeogenesis
catabolism of free fatty acids + depletion of fat stores & blood lipids (cholesterol)