Thyroid

Question 1

Anatomy of the thyroid gland

Answer 1

Follicles: balls consisting of a shell made of cells filled with colloid (where thyroglobulin is stored)

Parafollicular cells (synthesize calcitonin- not needed for normal physiology

Question 2

Chemistry of thyroid hormone

Answer 2

Tyrosine: amino acid precursor for thyroid hormone synthesis
Iodine+tyrosine= organified iodine
monoiodotyrosine= MIT one iodine attached
diiodotyrosine= DIT two iodines attached
Triodo thyronine= T3 formed as part of the thyroglobulin molecule from MIT and DIT
thyroxine= T4 formed as part of the thyroglobulin molecule from DIT and DIT

Question 3

Iodine mass balance

Answer 3

Intake must equal outtake in the steady state
500 ug is absorbed taken in thru intestines, absorbed and circulates as the ion iodide
about 1/4 is pumped into thyroid follicular cells (iodide pump) remaining is excreted in urine

of the 120ug thats pumped into thyroid follicular cells 60% is organified into thyroid hormones and 40 % leaks out into plasma to be excreted thru urine

of the 70 ug of iodide in thyroid hormones, 80% is deorganified in the tissues and excreted in urine and rest in feces

almost 97% of the absorbed iodide is eliminated thru urine

Question 4

Thyroid hormone synthesis

Answer 4

1. iodide is pumped into the follicular cells with sodium by the sodium iodide symporter (NIS) with the energy supplied by the NA/K ATPase
2. thyroglobulin is synthesized inside the follicular cell and secreted in the colloid space
3. Iodide is pumped indo the colloid and exchanged with CL via the pendrin transporter
4. As iodide passes thru to colloid its converted to I2
5. Peroxidase catalyzes several reactions:
   Peroxidase-> peroxide that make I2 very reactive so that it attaches to tyrosine on thyroglobulin (Tg)
   It catalyzes coupling of MIT and DIT and DIT and DIT to form T3 and T4 as part of the Tg molecule
6. when TSH stimulates the Follicular cell, pinocytosis of Tg as a colloid droplet stored in the colloid increases bringing in Tg with T3 and T4
7. Proteases in the follicular cell liberate TG and T3 and T4 and MIT and DIT from the Tg molecule
8. T3 and T4 is secreted in the extracellular space and MIT and DIT is recycled as iodide and tyrosine and other Tg

Question 5

Half life of Thyroid hormones

Answer 5

T4 and T3 are highly bound to circulating plasma proteins, so their half lives are very long
T4 has a half life of 7 days and T3 of about a day
Patients can miss a day of therapy without changes in T serum levels

Question 6

Binding of Thyroid hormones in plasma

Answer 6

T4 is bound to thyroid binding globulin (TBG), transthyretin and loosley bound to albumin so that less than .05% is free

T 3 doesnt bind to transthyretin so it circulates less tightly bound to plasma proteins than T4 so its half life is shorter

Question 7

Effects of thyroid hormone

Answer 7

1. T4 and T3 dissociate from the plasma binding protein, and diffuse directly into the target cell
2. T4 can be activated to T3 by target cell monodeiodinase and binds to thyroid hormone receptor in the nucleus (T3 binds more) and causes transcription and translation of new proteins
3. Growth and CNS development early in childhood
   Metabolic effect (increase in metabolic rate of O2 consumption in mito-> basal metabolic rate HOT
   Cardiovascular and Respiratory: increase in metabolism cardiac out put and ventilation

Thyroid hormones are sympathomimetic (they augment the sensitivity of catecholamines and sympathetic input to these tissues)

Question 8

Control of thyroid function

Answer 8

TSH is the regulator of Thyroid Function:
TSH stimulates Iodine uptake, thyroid hormone synthesis and secretion and thyroid growth
Increase in TH decreases TSH release
T4 is activated to T3 in target tissues
TRH (hypothalamic)

Question 9

Thyroid disease and treatment

Answer 9

Too little:
Primary/Hashimotos thyroditis - high TSH low TH (auto immune attach on glad)
secondary/hypopituitary- low TH, TSH not elevated

Too much: (ALMOST ALWAYS PRIMARY)
High free T4 and low TSH (Graves disease) (autoimmune diesase Thyroid stimulating immunoglobulins TSIs are produced that activate the TSH receptor, the increases in T4 in the blood suppress TSH

TSH secreting tumors are rare

Question 10

Maternal Thyroid hormone

Answer 10

Liver makes a lot of TBG due to estrogen
HcG goes up (has homology to TSH) and stimulates free TH, so TSH goes down
B/c TBG is high, adds to the total T4

At the end of pregnancy TSH and free T4 is normal (before pregnancy) (but total remains high)