Unit 5 - Thyroid and Antithyroid Drugs

Question 1

how does iodine get into the thyroid?

Answer 1

through an Na-I symporter
-since there is high extracellular Na+, and an Na/K pump keeps intracellular Na+ low, I can get inside at a constant rate

Question 2

what are diseases caused by defective Na-I smporters?

Answer 2

• symporter gene mutation - congenital hypothyroidism

- autoimmune (Hashimoto’s) thyroiditis) - Ab against the symporter itself

Question 3

what are the steps to thyroid hormone synthesis?

Answer 3

1. iodination of tyrosine to make DIT
2. addition of two DIT together to make T4 (thyroxin)

both are done by thyroid peroxidase enzyme

Question 4

how are thyroid hormones secreted?

Answer 4

iodinated thyroglobulin (T4) travels thru apical membrane to follicular cell in endosome, which combines with lsosome to free the T4 molecules, and diffuse into blood thru basal membrane
-free T4 binds with thyroxin-binding globulin for travel thru blood

Question 5

how is gene expression of thyroid hormones regulated?

Answer 5

T4 converts to T3 (more potent and lipophilic) to pass membranes to nucleus

• TH receptor (heterodimer made of TR monomer and RXR monomer), which is bound to TH response element (TRE)
• T3 binds TH-RXR-TRE complex to exert expression

Question 6

what are physiological effects of TH?

Answer 6

• O2 consumption
• metabolism of fat, CHO, PRO, vits
• secretion and breakdown of other hormones
• growth and differentiation

Question 7

what can Hashimoto’s thyroiditis be caused by?

Answer 7

-production of Ab against thyroid peroxidase, Na-I symporter, or thyroglobulin or TSH receptor

Question 8

what is myxedema?

Answer 8

severe form of hypothyroidism, especially in older women

Question 9

what are problems associated with treating hypothyroidism with hormone replacement therapies?

Answer 9

1. contains T3 (acts rapidly, causes variable blood levels)
2. varies in potency (not stable products, hard to control dose)
3. some patients are allergic to animal products

Question 10

what are 2 reasons TH replacement therapy is used?

Answer 10

1. replace function of gland

2. prevent further growth of thyroid tissue

Question 11

when should readjustment of TH dosage be done?

Answer 11

after 4-6 weeks of therapy with proper clinical and laboratory evaluation (serum levels of T4 and TSH)

Question 12

relationship between thyroid hormone and pregnancy?

Answer 12

a pregnant hypothyroid patient getting TH therapy needs to be monitored carefully
-too high or low levels could cause abnormal development

Question 13

what are strategies for hyperthyroid treatment?

Answer 13

1. subtotal thyroidectomy + replacement of T4
2. irradiate thyroid gland (I-131) + replacement of T4
   - I-131 is specific for thyroid, so not too much toxicity)
3. inhibit thyroid peroxidase activity (antithyroid drugs)
4. interfere with thyroid hormone facilitation of sympathetic activity (B-blockers)