THE EFFECT OF PROPYLTHIOURACIL ON SUBSEQUENT RADIOACTIVE IODINE THERAPY IN GRAVES-DISEASE

OBJECTIVE Antithyroidal drugs (ATD) are used in the management of Grav es' disease either as primary therapy for several months while awaitin g remission of the disease or as pretreatment for several weeks prior to definitive radioactive iodine therapy (RAI). We have reported previ ously that pretreatment with propylthiouracil (PTU) before definitive RAI therapy is associated with a higher RAI treatment failure rate tha n RAI therapy alone. The objectives of the current study were 2-fold. First, to verify the results of our prior study regarding the effect o f PTU used as pretreatment before RAI in a cohort of patients from a d ifferent institution and, secondly, to better define the relationship between the number of days off PTU before RAI therapy and therapeutic efficacy of RAI dosing. DESIGN A retrospective review of Graves' disea se patients treated from 1980 to 1994. PATIENTS Study patients had to meet the following inclusion criteria: radionuclide studies and thyroi d hormone values consistent with Graves' disease, at least 1 year of f ollow-up data available and discontinuation of the ATD at least 4 days before RAI administration. Exclusion criteria included therapy with a ny ATD other than PTU or ATD therapy during or following RAI dosing. M EASUREMENTS Effectiveness of RAI therapy, days on PTU, days off PTU an d calculated RAI dose to the thyroid were recorded for each subject. W e compared the efficacy of RAI therapy in patients treated with PTU (u sed either as pretreatment in preparation for RAI therapy or as primar y 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 hypothyroi d state. RESULTS One hundred and sixteen patients met our study criter ia. 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 dosi ng. Persistent hyperthyroidism was seen in 9% (7/76) of patients treat ed with RAI alone. The failure rate of a single dose of radioactive io dine was significantly increased when PTU was discontinued between 4 a nd 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 as sociated with a nearly 2-fold increase in failure rate, but this diffe rence did not achieve significance (17% vs 9% for RAI alone, P=0.24). Examining only those patients receiving PTU, patients who had successf ul single dose RAI therapy tended to receive a higher dose of RAI than patients failing RAI therapy (480 +/- 30 vs 410 +/- 40 MBq administer ed dose, P=0.18; and 8.0 +/- 0.9 vs 5.5 +/- 1.1 MBq/g thyroid tissue c alculated dose, P=0.21). Furthermore, total serum thyroxine at diagnos is was significantly higher in patients failing RAI therapy after PTU administration than in patients successfully treated with RAI after re ceiving PTU (316+/-40 vs 225 +/- 13 nmol/L, P=0.03). CONCLUSIONS Propy lthiouracil discontinued 4-7 days before radioiodine dosing is associa ted with a significant increase in the failure rate of a single dose o f radioiodine. Discontinuation of the propylthiouracil for at least a week before radioiodine administration is associated with a higher, al though not statistically significant, radioiodine failure rate. In pat ients that require treatment with propylthiouracil before radioiodine therapy, a higher total serum thyroxine lever at diagnosis is associat ed with an increased rate of radioiodine failure. Consideration should be given to increasing empirically the dose of radioiodine administer ed to Graves' disease patients that have received propylthiouracil wit hin a week of radioiodine administration in an effort to decrease the radioiodine failure rate to an acceptable level.