Disorders Of The Thyroid Gland

Question 1

Main functions of the thyroid gland

Answer 1

Facilitate growth and development
Modulate heat production
Modulate energy production

Question 2

Regulation of Feedback

Answer 2

TRH at 3 center, TSH at 2 center.
TRH——Thyrotrophin
Stimulates the synthesis and release of TSH
T3, T4 negatively inhibits TRH and TSH release
TSH is released in a pulsatile manner with a diurnal rhythm that peaks at midnight
Other inhibitors of TSH release include:
Dopamine
Steroid
Somatostatin

Question 3

TSH Action

Answer 3

Seven transmembrane G-protein coupled receptor
Gs’-alpha
stimulates the production of Adenalase cyclase which increase production of Cyclic AMP
Other factors stimulating TSH action; Insulin-like Growth Factor-1, Endothelial growth factor, Transformin Growth Factor, Endothelin’s, cytokines

Question 4

Biosynthesis of Thyroid Hormones

Answer 4

Derived from thyroglobulin.
-> Dietary Iodine absorption (10-25%) increased to about 60-70% under TSH stimulation.
-> Absorption through NIS - sodium iodine transporter; through salivary, lactating breast, and placenta.
-> Iodine converted to iodide.
-> Active transport of iodide from blood stream across follicular basement membranes into follicle (trapping)
-> Iodide is oxidized by thyroid peroxidase
-> Thyroid peroxidase mediates iodination of thyroid residues in thyroglobulin to form mono-iodotyrosine and di-iodotyrosine(coupling)
-> These membranes couple to form tetra-iodothyronine (T4 ) and tri-iodothyronine (T3)

Question 5

Steps in the biosynthesis and secretion of thyroid hormones (in the thyroid follicular cells

Answer 5

Iodine transport
Thyroglobulin synthesis
Oxidation of iodine
Organification (iodination)
Coupling
Storage
Secretion

Question 6

Transport and Metabolism of Thyroid hormones

Answer 6

80% of thyroid hormones are bound to Thyroid binding globulin, followed by 10% bound to thyroxine binding prealbumin (TBPA) or transthyretin
10% bound to albumin

T4 binds at least 10 times more than T3 (So T4 is the storage hormone)

Question 7

Reason for Binding of Thyroid Hormones (Transport and Metabolism)

Answer 7

To delay clearance of hormones
Increase the pool of thyroid hormones
Modulate hormone delivery to active sites

Question 8

Abnormalities of Binding Proteins (affect thyroid function tests) - X-Linked thyroid binding globulin deficiency

Answer 8

Manifests as
Decrease Total T4
Decrease Total T3
Euthyroid
Normal TSH (Free T3 and T4 are normal, it’s just the binding to the TBG that is different)

Question 9

Abnormalities of Binding Proteins - Mutations of TBG, TTR, and Albumin (Leads to and manifests as)

Answer 9

Causes euthyroid hyperthyroidism or Familial dysalbuminemic hyperthyroidism (FDH)

Manifests as
Increased Total T4 and or Total T3
Unbound / Free hormone is normal
FDH is autosomal dominant