Thyroid I

Question 1

What are the C cells?

Answer 1

cells in the thyroid that produce calcitonin

Question 2

How is iodine transported into the thyroid cell? What factors stimulate iodine transport into the thyroid?

Answer 2

NaI transporter or Na I symporter
located on the basolateral surface of the cell
stimulated by TSH and intracellular cAMP

Question 3

What drugs act on the NaI symporter?

Answer 3

perchlorate and thiocyanate

Question 4

How is iodine transported out of the cells? To where is it transported?

Answer 4

transported to the follicular lumen by Pendrin
this is on the apical membrane of follicular cells
also found in inner ear and kdiney
positively regulated by luminal thyroglobulin

Question 5

What problems are caused by pendrin mutations?

Answer 5

deafness and goiter

Question 6

How is thyroid hormone synthesized?

Answer 6

certain tyrosine of thyroglobulin are iodinated by TPO (thyroid peroxidase) and H2O2. This results in formation of MIT and DIT.
T3: MIT + DIT. coupled with H2O2 and TPO
T4: 2 DIT

Question 7

What does TSH do to the thyroid

Answer 7

stimuates thyroglobulin synthesis, NIS and TPO

Question 8

What is the Wolf-Chaikoff Effect?

Answer 8

high levels of ECF iodide increase iodide transport and organification up to a certain limit
then, there is a sudden decrease in synthesis: Wolf-Chaikoff effect
inhibition is brief- there is escape after a few days.
may be important, especially with contrast media or amiodarone

Question 9

What is important to know about relative secretion and metabolism of T3 and T4? Half-lives?

Answer 9

The thyroid mostly secretes T4. If you need T3, you can make it in the periphery by metabolism of T4. T4 can also be metabolised to rT3 in the periphery, which is inactive.
T3 half life: 4-7 min
T 4 half-life: 7 days. Takes at least a month to reach a steady state

Question 10

D1 deiodinase: location, role

Answer 10

primary peripheral deiodinase that converts T4 to T3

rapid kinetics- not easily saturated

Question 11

D2 deiodinase location, role

Answer 11

primary deiodinase in the brain and pituitary that converts T4 to T3

Question 12

D3 deiodinase location, role

Answer 12

deiodinase that inactivates T4 by conversion to rT3. helps keel brain T3 levels constant

Question 13

thyroid hormone binding proteins: important actors and differences btw T4 and T3

Answer 13

An even greater percentage of T4 is bound than T3. both bound by thyroid binding globulin and albumin (and thyroid-binding pre-albumin), though in different percentages

Question 14

Hypothalamic-pituitary axis and control of thyroid: stimulatory agents, other affects of stimulatory agents. What else is similar to TSH, structurally? What is the significance of that?

Answer 14

TRH released by hypothalamus and stimualtes TSH release. TRH also stimulates prolactin release
TSH is secreted by the pituitary. Has alpha and beta subunits. Alpha subunit is identical to alpha subunit of FSH, LH, and HCG, and there may be some cross-reactivity
TSH receptors on follicular cells stimulate thyroid hormone production

Question 15

What feedback exists for the hypothalamic pituitary axis?

Answer 15

T3 attenuates the ability of thyrotrophs in the pituitary to respond to TRH
T3 directly blocks TRH secretion by the hypothalamus
T3 decreases transcription of TSH genes and decreases transcription of pro-TRH gene

Question 16

What are some additional inhibitors of TSH secretion?

Answer 16

dopamine (esp. relavant in pts who are given dopamine as a pressor agent), somatostatin, and glucocorticoids

Question 17

To review: how is thyroid hormone regulated?

Answer 17

iodine uptake into the thyroid gland
iodination of thyroglobulin by TPO
release of thyroid hormone
de-iodination of thyroid hormone
thyroid hormone binding to protein
hypothalamus/pituitary action