What medication is appropriate for a patient with hyperthyroidism, indicated by high Triiodothyronine (T3) and Thyroxine (T4) levels?

Antithyroid Medication for Hyperthyroidism

For a patient with elevated T3 and T4 indicating hyperthyroidism, methimazole is the preferred first-line antithyroid medication in most situations due to its superior efficacy, longer half-life allowing once-daily dosing, and lower risk of severe adverse effects compared to propylthiouracil. 1, 2, 3

Primary Treatment Selection

Methimazole should be the default choice for treating hyperthyroidism except in specific circumstances outlined below 2, 3:

• Methimazole inhibits thyroid hormone synthesis more effectively than propylthiouracil 1, 2
• The longer half-life permits once-daily administration, improving adherence 2
• Methimazole has fewer severe adverse effects, particularly lower risk of hepatotoxicity 2, 3
• Both medications have similar cost profiles 2

When Propylthiouracil Is Preferred

Switch to propylthiouracil in these specific clinical scenarios 4, 5, 6:

First Trimester Pregnancy

• Propylthiouracil is the mandatory choice during pre-pregnancy planning and the first 16 weeks of gestation 2, 5
• Methimazole carries risk of severe teratogenic effects including aplasia cutis congenita (123-fold increased risk) and exomphalos (22-fold increased risk) 6
• After the first trimester, consider switching back to methimazole for the second and third trimesters to avoid maternal hepatotoxicity risk from propylthiouracil 4

Thyroid Storm or Severe Thyrotoxicosis

• Propylthiouracil has the additional benefit of blocking peripheral conversion of T4 to T3, which methimazole does not provide 7
• In patients treated with propylthiouracil plus iodide, serum T3 decreased more rapidly (to 326 ng/100 mL on day 1) compared to methimazole plus iodide (568 ng/100 mL on day 1) 7
• The T4/T3 ratio increased more substantially with propylthiouracil (from 43 to 88 by day 2) versus methimazole (from 35 to 52 by day 2), confirming inhibition of peripheral T3 production 7

Mechanism of Action

Both medications work by inhibiting thyroid hormone synthesis but do not affect existing circulating hormones 1:

• Neither drug inactivates thyroxine or triiodothyronine already stored in the thyroid or circulating in blood 1
• Neither interferes with effectiveness of exogenous thyroid hormones given orally or by injection 1
• Both are readily absorbed in the gastrointestinal tract, metabolized in the liver, and excreted in urine 1

Critical Safety Monitoring

For Methimazole

Monitor for agranulocytosis (4-fold higher risk than propylthiouracil) 6:

• Instruct patients to immediately report sore throat, fever, or signs of infection 4
• Obtain white blood cell count with differential if any symptoms of illness develop 4

For Propylthiouracil

Monitor for hepatotoxicity and ANCA-associated vasculitis 4, 6:

• Check liver function tests (bilirubin, alkaline phosphatase, ALT/AST) particularly in the first 6 months 4
• Patients must report symptoms of hepatic dysfunction: anorexia, pruritus, jaundice, light-colored stools, dark urine, right upper quadrant pain 4
• ANCA-associated vasculitis has 29.84-fold higher risk with propylthiouracil, including rapidly progressive glomerulonephritis (6.44-fold) and pulmonary alveolar hemorrhage (7.77-fold) 6
• Instruct patients to report new rash, hematuria, decreased urine output, dyspnea, or hemoptysis immediately 4

Common Pitfalls to Avoid

• Never use methimazole in the first trimester of pregnancy due to severe teratogenic risks including congenital malformations 2, 6
• Do not continue propylthiouracil long-term in non-pregnant patients when methimazole would be safer, as propylthiouracil carries higher hepatotoxicity risk 4, 2
• Avoid assuming both drugs are interchangeable - propylthiouracil's unique ability to block peripheral T4 to T3 conversion makes it specifically valuable in thyroid storm 7
• Do not overlook the need for close surveillance - both drugs require monitoring for agranulocytosis, with patients instructed to report any signs of infection immediately 4