Endocrinology of the Thyroid Gland Flashcards
Describe the structure and function of a thyroid follicle
1) A sphere of follicular cells surrounding colloid inner core, mainly contains thyroglobulin
2) Basolateral membrane (exterior) contains G-coupled receptors for TSH
3) Produces thyroid hormone
Describe the synthesis of thyroid hormone (8 steps).
1) Iodide is taken up from blood by follicular iodide pump on basolateral membrane, coupled to Na/K ATPase
2) Iodide diffuses down gradient into the follicular space (through follicular cells)
3) Iodide is oxidized via thyroperoxidase + H2O2
4) Thioperoxidase then iodizes tyrosine residues on thyroglobulin (mono- or di-iodoTyr, aka MIT or DIT)
5) 2 DIT condense to form T4 OR 1 DIT + 1 MIT condense to form T3 on TG
6) TG is phagocytosed by follicular cell, degraded in lysosomes to amino acids, MIT, DIT, T3 and T4
7) T3/T4 are released into blood
8) MIT/DIT are deiodinated & recycled
- via thyroxine deiodinase, inhibited by PTU
What molecules modulate the activity of the iodide pump, thus affecting TH synthesis?
1) Stimulated by TSH
2) Inhibited by
- thiocyanate (inavtivation)
- Perchlorate (CI)
- Perrhenate (CI)
- Pertechnetate (CI)
Which inhibitor of TH synthesis is different from most others and why?
Propylthiouracil (PTU) inhibits most steps of TH synthesis, but does NOT inhibit the iodide pump.
How is thyroperoxidase regulated?
Stimulated by TSH, inhibited by PTU
What are the major functions of thyroxine deiodinase?
1) Recycles MIT and DIT in thyroid follicle
2) Converts T4 to T3 in periphery
- may remove wrong I to form inactive rT3
What are the 4 thiourea drugs? What is their function?
Antithyroid drugs:
1) thiourea
2) thiouracil
3) polythiouracil
4) methimazole
What are the indications for use of PTU vs/ methimazole?
1) Methimazole is drug of choice
- but causes 1st trimester birth defects
2) PTU causes severe liver damage
- used in 1st trimester of pregnancy
- methimazole allergy
- thyroid storm (met doesn’t prevent conversion of T4 to T3)
How are T3/T4 transported? How much hormone is free in bloodstream? How long are their half-lives?
T3/T4 bind TBG (thyroid binding globulin)
- 3% T3 is free, 1.5 day half-life
- 03% of T4 is free, 6.5 day half-life
How are TH levels regulated? What is the best measure for hyper/hypothyroidism?
1) TH is regulated by negative feedback, so high TH decreases levels of TRH & TSH, and low levels of TH increase levels of TSH & TRH
2) TSH is the best measure since circulating T3/T4 levels may fluctuate
Describe endemic goiter.
Enlarged thyroid gland caused by low levels of iodine in the diet.
-Low TH results in oversecretion of TSH leading to thyroid hypertrophy
Describe congenital hypothyroidism
Insufficient TH production due to dysfunctional thyroid gland.
-Leads to cretinism if untreated (severely stunted physical & mental growth & development)
Describe Grave’s disease
Autoimmune disorder that produces Thyroid Stimulating Immunoglobulins (TSI): bind TSH receptor regardless of TSH levels
- Leads to hyperthyroidism
- Also present with exophthalmos (eye bulging) due to immune rxn behind eye
What is the effect of taking exogenous Growth Hormone on thyroid activity?
GH upregulates somatostatin, which will inhibit TSH and lead to hypothyroidism
Describe Hashimoto’s thyroiditis
Autoimmune disorder characterized by production of autoantibodies against thyroglobulin or thyroperoxidase, leading to destruction of thyroid tissue and hypothyroidism.
- Often concurrent with Grave’s diseaese
- Here, hyper/hypothyroid determined by prevalence of respective antibodies
What is the Wolff-Chaikov effect?
While low iodine increases TH synthesis, HIGH intake of iodine will INHIBIT TH synthesis. May be used to treat thyroid storm.
What is a thyroid storm?
Rare occurrence in which a patient produces severely high levels of T3/T4 in response to physical stress such as surgery, leading to dangerous CV complications
What does “organification” refer to?
Iodination of tyrosine residues
What structure is left when T3/T4 is cleaved from thyroglobulin?
Dehydroalanine
What is the daily requirement for iodine?
30% of consumed iodine is absorbed
150µg needed daily for T3/T4 containing 50 µg iodide
What tissues can take up iodine?
Thyroid (can oxidize)
Salivary glands, mammary glands, chorion, & stomach can take up iodine but can’t oxidize
What is the concentration gradient of iodine inside and outside the follicular cell?
500:1
Describe thyroperoxidase
1) Requires H2O2, produced by NADPH-dependent enzyme resembling cytochrome C reductase
2) Occurs on luminal surface & inhibited by thiourea drugs (PTU)
3) Synthesis stimulated by TSH
How are thyroid hormones stored?
Stored in thyroid follicles as thyroglobulin (in colloid)
