Peter S. Bernstein, MD, MPH, FACOG; Karen L. Koscica, DO

Disclosures

June 19, 2003

Question

What is the maximum dose of propylthiouracil (PTU) that one can prescribe to a pregnant patient?

Response from Peter S. Bernstein, MD, MPH, FACOG and Karen L. Koscica, DO

Hyperthyroidism complicates approximately 0.2% of pregnancies. It is the second most common endocrine disorder seen in pregnancy, second only to diabetes mellitus. The most common cause is Graves disease, which accounts for approximately 85% of the cases. It is an important entity to consider during pregnancy because of the increased risk to mother and fetus.[1]

The laboratory diagnosis of hyperthyroidism consists of a screening serum thyroid-stimulating hormone (TSH) level and serum levels of free triiodothyronine (T3) and free thyroxine (T4).The TSH is low when measured levels are < 0.1 mlU/L. In normal first trimester pregnancies, levels can be as low as 0.1-0.5 mlU/L; the diagnosis of hyperthyroidism in this situation can only be diagnosed if the free T3 and free T4 levels are elevated.[2]

The mainstays of hyperthyroidism treatment are antithyroid drugs. The thioamides are the drugs used in treatment during pregnancy. The 2 principal medications are propylthiouracil (PTU) and methimazole. Their function is to block thyroid hormone biosynthesis. The dosage of methimazole sufficient to control hyperthyroidism is 15-100 mg daily, administered as divided doses 3 times daily. The appropriate dosage of PTU can range from 300 mg daily to a maximum dose of 1200 mg daily in divided doses 3 times daily. Once serum thyroid hormone levels return to normal, it is necessary to decrease the dosage to 5-20 mg daily of methimazole or 50-300 mg daily for PTU in divided doses. When doses of PTU are > 300 mg/day or > 20 mg/day for methimazole are taken long term, fetal goiter and hypothyroidism may result.[2] This is why it is important to decrease the dosage after levels return to normal. TSH levels should be checked every 3-4 weeks to assess thyroid function. The free T3 and T4 levels should be just above the normal range.

Adverse reactions may occur with these medications. Approximately 10% of patients will experience a skin rash. The most rare complication is agranulocytosis, which occurs in approximately 1 in 200 pregnancies. This is reversible once the medication is discontinued. A baseline white blood cell count is recommended.[2] Both drugs cross the placenta, but PTU does so less readily than methimazole. Aplasia cutis was described in 20 infants exposed in utero to methimazole. The risk of this occurrence when using this medication is unknown, but no such adverse reactions to the fetus have been described with the use of PTU. This is a reason why PTU is preferred over methimazole.[2]

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