The effect of propylthiouracil on subsequent radioactive iodine therapy in Graves' disease

Antithyroidal drugs (ATD) are used in the management of Graves' disease either as primary therapy for several months while awaiting remission of the disease or as pretreatment for several weeks prior to definitive radioactive iodine therapy (RAI). We have reported previously that pretreatment with propylthiouracil (PTU) before definitive RAI therapy is associated with a higher RAI treatment failure rate than RAI therapy alone. The objectives of the current study were 2-fold. First, to verify the results of our prior study regarding the effect of PTU used as pretreatment before RAI in a cohort of patients from a different institution and, secondly, to better define the relationship between the number of days off PTU before RAI therapy and therapeutic efficacy of RAI dosing.

A retrospective review of Graves' disease patients treated from 1980 to 1994.

Study patients had to meet the following inclusion criteria: radionuclide studies and thyroid hormone values consistent with Graves' disease, at least 1 year of follow-up data available and discontinuation of the ATD at least 4 days before RAI administration. Exclusion criteria included therapy with any ATD other than PTU or ATD therapy during or following RAI dosing.

Effectiveness of RAI therapy, days on PTU, days off PTU and calculated RAI dose to the thyroid were recorded for each subject. We compared the efficacy of RAI therapy in patients treated with PTU (used either as pretreatment in preparation for RAI therapy or as primary long-term therapy) before RAI administrations to those treated with RAI alone with special attention to the number of days on and off PTU before RAI dosing. Patients were considered RAI treatment failures if a second dose of RAI was required to achieve a euthyroid or hypothyroid state.

One hundred and sixteen patients met our study criteria. Forty patients received PTU therapy for a mean of 221 +/- 59 days. The PTU was discontinued for a mean of 60 +/- 25 days before RAI dosing. Persistent hyperthyroidism was seen in 9% (7/76) of patients treated with RAI alone. The failure rate of a single dose of radioactive iodine was significantly increased when PTU was discontinued between 4 and 7 days before the administration of RAI (29% vs 9% for RAI alone, P = 0.039). PTU discontinued for at least 1 week before RAI dosing was associated with a nearly 2-fold increase in failure rate, but this difference did not achieve significance (17% vs 9% for RAI alone, P = 0.24). Examining only those patients receiving PTU, patients who had successful single dose RAI therapy tended to receive a higher dose of RAI than patients failing RAI therapy (480 +/- 30 vs 410 +/- 40 MBq administered dose, P = 0.18; and 8.0 +/- 0.9 vs 5.5 +/- 1.1 MBq/g thyroid tissue calculated dose, P = 0.21). Furthermore, total serum thyroxine at diagnosis was significantly higher in patients failing RAI therapy after PTU administration than in patients successfully treated with RAI after receiving PTU (316 +/- 40 vs 225 +/- 13 nmol/L, P = 0.03).

Propylthiouracil discontinued 4-7 days before radioiodine dosing is associated with a significant increase in the failure rate of a single dose of radioiodine. Discontinuation of the propylthiouracil for at least a week before radioiodine administration is associated with a higher, although not statistically significant, radioiodine failure rate. In patients that require treatment with propylthiouracil before radioiodine therapy, a higher total serum thyroxine level at diagnosis is associated with an increased rate of radioiodine failure. Consideration should be given to increasing empirically the dose of radioiodine administered to Graves' disease patients that have received propylthiouracil within a week of radioiodine administration in an effort to decrease the radioiodine failure rate to an acceptable level.