Current diagnostic studies [radioiodine uptake and serum thyroglobulin (Tg) levels] for residual or metastatic thyroid tissue in patients with differentiated thyroid carcinoma require a hypothyroid status necessary for adequate endogenous TSH stimulation. However, almost all patients have symptoms of clinical hypothyroidism during this period. As shown in the present study, recombinant human TSH (rhTSH) allows stimulation of 131I uptake and Tg release from residual thyroid tissue in euthyroid patients. To assess safety, dosage, and preliminary efficacy, comparison was made of the stimulation of 131I uptake and Tg release after rhTSH administration and after T3 withdrawal in 19 patients after a recent thyroidectomy for differentiated thyroid carcinoma. Various doses (10-40 U) of rhTSH were injected im for 1-3 days in patients receiving suppressive doses of T3. Twenty-four hours after the last dose of rhTSH, 1-2 mCi 131I were administered, followed by a neck and whole body scan 48 h later. After discontinuing T3 for a median period of 19 days (range, 15-28), endogenous serum TSH levels were markedly elevated, and the patients were given a second dose of 131I and rescanned 48 h later. The injections of rhTSH were tolerated well. No major adverse effects were reported; nausea was reported in 3 (16%) and vomiting in 1 of the patients treated with high doses. The quality of life, as measured by two psychometric scales, was far better during rhTSH treatment than after T3 withdrawal. The peak levels of serum TSH (mean +/- SD) after a single dose of 10, 20, or 30 U were 127 +/- 19, 309 +/- 156, and 510 +/- 156 mU/L, respectively, and occurred 2-8 h after injection. Twenty-four hours after the injection, TSH levels decreased to 83 +/- 31, 173 +/- 73, and 463 +/- 148 mU/L in these treatment groups, respectively. The quality of the thyroid scans and the number of sites of abnormal 131I uptake were similar after rhTSH treatment and in the hypothyroid scans in 12 (63%) patients. Two additional sites of uptake in the chest and one in the thyroid bed, not visible on the hypothyroid scans, were identified in 3 (16%) patients after rhTSH. In 1 patient a focus of uptake was better visualized after rhTSH than after withdrawal. In 3 (16%) other patients, 1 lesion in the chest and 2 in the neck were seen only after T3 withdrawal.(ABSTRACT TRUNCATED AT 400 WORDS)