Thyroid Drugs

Question 1

Thyroid hormone synthesis early steps

Answer 1

• Iodine converted to iodide in gut
• Taken up into follicular cell via Na+/I- symporter (NIS) = Iodide Trapping
• Transported by pendrin into colloid

Question 2

Later steps of thyroid hormone synthesis

Answer 2

• Iodination of thyroglobulin - thyroid peroxidase (TPO) causes organification of iodide by oxidizing it and then I is attached to tyrosine residues of thyroglobulin to form MIT (mono-I) and DIT (di-I)
• Coupling - TPO catalyzes formation of T3 (MIT+DIT) and T4 (DIT+DIT)
• Storage in colloid
• Release via pinocytosis of Tg, lysosomes with peptidases digest Tg and T3/T4 released

Question 3

In blood, T3/T4 bound to

Answer 3

• TBG - thyroxine binding globulin; increased with estrogen/oral contraceptives; carries most
• Transthyretin
• Albumin
• Normally only ~.1% unbound and accessible

Question 4

T3 entered cells directly

Answer 4

T4 converted to T3 by seleno-deiodinases first

then T3 binds nuclear receptor

Question 5

TRH

Answer 5

Hypothalamus peptide

• Release in response to cold temperatures
• Inhibited by dopamine, somatostatin, glucocorticoids

Question 6

TSH activates

Answer 6

GPCR on thyroid, increasing cAMP which increases biosynthesis of T3/T4 by up regulating virtually all the involved components

Question 7

Levothyroxine, Liothyronine, Thyrolar, Armour Thyroid

Answer 7

Thyroid hormone replacement for hypothyroidism

• Levothyroxine (T4) - long half-life takes 6-8 weeks for steady state concentration
• Liothyronine (T3) - quick onset/offset, can cause tachycardia or jitteriness
• Thyrolar - T3/T4 combination
• Armour thyroid - natural preparation of T3/T4

Question 8

Autoimmune Polyglandular Syndrome/Schmidt’s Syndrome

Answer 8

Hypothyroid + adrenal insufficiency

- Treat adrenal insufficiency first with glucocorticoids since LT4 will exacerbate it

Question 9

Hypothyroid women when pregnant require

Answer 9

more LT4 replacement because of estrogen increasing TBG, so less free hormone

Question 10

Atenolol, propranolol

Answer 10

Beta-blockers treat the symptoms of hyperthyroid

• Atenolol - B1 selective
• Propranolol - also decreases T3 concentration via inhibition of Type 1 5’-deiodinase which converts T4 to T3; this is a small effect though

Question 11

Radiotherapy (131-I as sodium iodide salt)

Answer 11

• Not for children or pregnant women; but virtually all take up by thyroid
• Destroys thyroid so lifetime hormone replacement after
• Treat Graves’ disease

Question 12

Thionamide Therapy - propylthiouracil (PTU) or methimazole (MMI)

Answer 12

“anti-thyroid drugs”

• PTU inhibits TPO & Type I 5’-deiodinase; good for pregnant/nursing b/c only small amount crosses placenta/milk; risk of hepatic failure
• MMI - only inhibits TPO; teratogenic during pregnancy
• Narrow therapeutic windows, cross-allergies from one to the other

Question 13

Iodine (potassium iodide solutions or potassium iodide-iodine)

Answer 13

• Must give thionamide first to block TPO
• blocks thyroid hormone release, inhibits iodine organifiction, decreases vascularity of gland
• used before thyroidectomy, for thyroid storm, and to victims of radioactive fallout

Question 14

Lithium

Answer 14

Inhibits thyroid hormone secretion by inhibiting iodide transport into thyroid; may decrease pinocytosis

Question 15

Dexamethasone

Answer 15

Inhibits T4 to T3 conversion

- Useful in thyroid storm

Question 16

Thyrogen/Thyrotropin Alfa

Answer 16

synthetic TSH used to stimulate thyroid cancer cells ~6 months after surgery so they “reveal themselves”
- Also used to stimulate uptake of radioactive I-131 to kill leftover thyroid or cancer cells