1-28 Thyroid DSA

Question 1

What is thyroxine?

Answer 1

T4

Less affinity for thyroid hormone receptor

Question 2

What is triiodothyronine?

Answer 2

T3

Question 3

What is the regulatory hormone for thyroid hormone biosynthesis? Where is it produced, and what is it regulated by?

Answer 3

TSH, produced by ant. pit., controls production of thyroid hormone

TSH is under negative feedback inhibition of thyroid hormone

TSH controls each step in the synthesis of thyroid hormones

Question 4

What mediates hypothalamic/pituitary control of thyroid hormone secretion?

Answer 4

Starts with TRH

• called thyrotropin releasing hormone
• secreted by hypothalamus
• stimulates secretion of TSH by ant. pit.

Question 5

What is the mechanism for TSH?

Answer 5

Increases synthesis and secretion of thyroid hormones by follicular cells
- works via adenylate cyclase cAMP mechanism

Question 6

What role does T3 play in TSH secretion?

Answer 6

T3

• down-regulates TRH receptors in ant. pit.
• inhibits TSH secretion

Question 7

What role does IgG play in controlling thyroid hormone release?

Answer 7

IgG Ab to TSH receptors

Act in an agonist fashion

• stimulates thyroid gland to secrete T3 and T4
• works by binding TSH receptors

Question 8

What are the 8 steps in thyroid hormone synthesis, in a general sense?

Answer 8

1. Thyroglobin
   - synthesized and released into follicle cell lumen
2. I-/Na+ Cotransport
   - pulls I- into follicle cell for thyroid hormone
3. Oxidation of I- to I2
   - done by peroxidase enzyme
   - allows incorporation of I2 onto thyroid hormone
4. Organification of I2
   - tyr residues from thyroglobulin incorporate I2 onto hormone structure

5. Coupling of MIT and DIT
MIT - 1 iodine DIT = 2 iodines
2 DITs = T4
1 DIT + 1 MIT = T3
More T4 is made, generally

6. Stimulation of cells by TSH
   - pulls T4 or T3 back into follicle cells so that carrier protein (thyroglobin) is pulled off by lysosomes
   - T3 or T4 released into circulation
7. Binding of T3 and T4
   - in circulation, done by thyroxine binding globin
8. Conversion of T4 to T3
   - T3 more biologically active
   - done via 5’ iodinase

Question 9

What are the cellular locations for thyroid hormone biosynthesis?

Answer 9

Most synthesis takes place in thyroid follicular cells

- some final modifications take place on target cells

Question 10

How is thyroid hormone transported in circulation?

Answer 10

Most thyroid hormone is bound to thyroxine binding globulin (TBG)
- increases half life of thyroid hormone

Only free thyroid hormone is active, so changes in TBG levels change fraction of free circulating thyroid hormone
- free circulating hormone has negative feedback on TSH secretion, affecting synthesis of more T3 & T4

Question 11

What can lead to decrease of TBG levels?

Answer 11

Hepatic failure

• decrease in hepatic TBG production
• normal levels of free hormone, but with transient increase in free hormone
• leads to negative feedback on TSH

Question 12

What can lead to an increase of TBG levels?

Answer 12

Pregnancy

• impaired hepatic breakdown of TBG
• decreased free thyroid hormone
• increase in TSH synthesis

Question 13

What is the action of 5’ iodinase?

Answer 13

Converts T4 to T3 in peripheral tissues

• T3 more biologically active than T4
• can also make rT3, which is inactive

Question 14

What are the actions of thyroid hormone, in a basic sense?

Answer 14

1. Growth
   - height and bone formation
2. CNS
   - perinatal - development of CNS
   - adulthood - hyper and hypothyroidism
3. ANS
   - upregulates beta 1 adrenergic receptors in heart
4. BMR
   - increases it
   - increases O2 consumption, Na+/K+ ATPase
5. CV and respiratory systems
   - increases CO and ventilation
6. Metabolic effects
   - increased glycogenolysis, gluconeogenesis, glucose oxidation
   - increased catabolic effects due to need for substrates for exergonic reactions due to increased O2 intake