Thyroid Pharmacology

Question 1

what activates HPT axis?
what inhibits HPT axis?
how is thyroid hormone synthesized?

Answer 1

Hypothalamic-pituitary-thyroid axis can be activated by circadian rhythms, prolonged cold exposure or acute psychosis; severe stress can suppress activation
Pituitary release of TSH stimulated by hypothalamic TRH and inhibited by somatostatin, dopamine and glucocorticoids

Biosynthesis of Thyroid Hormones.

• controlled at all steps by TSH.
  1. Uptake of I- (iodide ion) into thyroid gland is stimulated by TSH via a Gs receptor
• blocked by SCN-, ClO4-, and I- Lithium ions

2. Iodide organification. I- oxidized and incorporated into tyrosine residues on thyroglobulin [Tg] molecules (mono-[MIT] and di-iodinated [DIT] tyrosine) via TPO
3. Coupling of precursors occurs on Tg (T4 / T3 ratio of 5:1 on thyroglobulin molecule); also mediated via thyroid peroxidase. MIT + DIT –> T3, DIT + DIT –> T4
   Retrieved from storage in lumen (large capacity) by pinocytosis; slowly released from gland by proteolysis (in T4/T3 ratio of 12-14:1)
   -proteolysis blocked by I

Question 2

2. Explain the treatment of hypothyroidism.

Answer 2

Replacement therapy - levothyroxine (T4)

-Free T4 and TSH should be monitored
Resolution of symptoms begins within 2-3 weeks of initiating therapy, but requires 6-8 weeks after starting with given dose to reach steady-state plasma levels.

Thyroid function tests (TSH levels) should be assessed 6-8 weeks after dosage adjustments are made

and then every 6-12 months after euthyroid state obtained

Pregnancy may require increased dose due to increased levels of TBG (via elevated estrogen) and increased placental metabolism of T4-T3.

Question 3

Drugs that mess with thyroid hormone

Answer 3

lithium, amiodarone, cholestyramine, phenytoin, carbamazepine

Question 4

activating enzyme (T4–> T3) inhibited by

Answer 4

GCorticoids, Beta blockers, amiodarone, Propylthiouracil

Question 5

whats avg. dose increase in pregnancy

Answer 5

25%

Question 6

Myxedema Coma

Answer 6

acute medical emergency, large doses of T4 required, hydrocortisone to prevent adrenal crisis

Question 7

Levothyroxine

Answer 7

synthetic T4, low cost

Question 8

Clinical considerations in medical management of Graves disease include:

A. Concern for agranulocytosis with use of thionamides
B. More rapid achievement of euthyroid state with methimazole vs PTU
C. Possibility of life-threatening hepatotoxicity with methimazole
D. Thionamides are more effective in patients with low uptake (RAIU)
E. Beta-blockers are used to control cardiovascular symptoms while euthyroidism is being achieved
F. PTU has a greater level of binding to plasma proteins than methimazole which may be advantageous in pregnant patients

Answer 8

A. Concern for agranulocytosis with use of thionamides
B. More rapid achievement of euthyroid state with methimazole vs PTU

E. Beta-blockers are used to control cardiovascular symptoms while euthyroidism is being achieved
F. PTU has a greater level of binding to plasma proteins than methimazole which may be advantageous in pregnant patients

Question 9

Relative to levothyroxine (T4), triiodothyronine (T3):

A. Has greater oral bioavailability
B. Has a longer duration of action
C. Has a greater affinity for thyroid hormone receptors
D. Is considered a prohormone for levothyroxine
E. Is required for most patients to adequately reduce symptoms of hypothyroidism
F. Has a greater potential for cardiovascular side effects during initiation of therapy
G. Is more expensive

Answer 9

A. Has greater oral bioavailability
C. Has a greater affinity for thyroid hormone receptors
F. Has a greater potential for cardiovascular side effects during initiation of therapy
G. Is more expensive

Question 10

Liothyronine

Answer 10

good bioavailability
short t1/2
avoid in patients with CVD
high cost

Question 11

Liotrix

Answer 11

4:1 mix of T4 and T3

not recommended

Question 12

Thyroid USP

Answer 12

dessicated porcine thyroid extract containg T3 and T4
variable ratio and content
use should be avoided

Question 13

DDI of T4

Answer 13

synergisitc adrenergic effect when taken with sympathmimetics like psuedoephedrine-phenylephrine

Question 14

Methimazole-Propylthiouracil

Answer 14

Thioamides
inhibits synthesis of thyroid hormone (TPO)

Methimazole more rapid achievement of euthyroid state than TPU
-rash, agranulocytosis

caution in pregnancy (PTU safer-because it has higher plasma protein bindings
-PTU-hepatotoxic rare but can be fatal

Question 15

Beta blockers

Answer 15

reduce hyperadrenergic state

Question 16

radioactive I 131

Answer 16

kills cells by Beta radiation in weeks to months

can cause release of stored T3 “radiation thryroiditis”

Question 17

SSKI/Lugol’s solution

Answer 17

inhibits T4/T3 synthesis and release
rapid onset and can be used in thryoid storm
cn be used prior to thyroid surgery since it decreases size and vascularity of thyroid

Question 18

Multiple medications are utilized in the management of thyroid storm. Which agent is most effective in blocking the release of preformed thyroid hormone from the gland?

Hydrocortisone
Metoprolol
Potassium Iodide
Propranolol
Propylthiouracil
Sodium Iodide

Which of the above is utilized to “protect” the thyroid gland from exposure to radioactive iodine following a nuclear plant “meltdown”?

Answer 18

Potassium Iodide
Sodium Iodide

KI