Evaluation of various doses of recombinant human thyrotropin in patients with multinodular goiters.

OBJECTIVE: To assess the safety, adverse effects, and radioactive iodine uptake (RAIU) of recombinant human thyrotropin (rhTSH) using a range of doses in patients with multinodular goiters.

METHODS: In this open-label study conducted between June 2002 and December 2004, euthyroid patients with small nontoxic multinodular goiters and normal thyrotropin concentrations were recruited from 4 sites in the United States. Baseline assessments included thyroid function tests, electrocardiogram, Holter monitoring, hyperthyroid symptom scale, flow-volume loop, and measurement of thyroglobulin and thyroperoxidase antibodies. Patients had a baseline 24-hour scan and thyroid iodine I 123 ((123)I) uptake evaluated at 6, 24, and 48 hours after rhTSH administration. Each patient received a single intramuscular injection of 0.03-mg, 0.1-mg, or 0.3-mg rhTSH followed 24 hours later by 400 microCi (123)I orally. Iodine 123 uptakes were again measured 6, 24, and 48 hours later, and a scintigram scan was performed at 24 hours. Thyroid function tests, flow-volume loop, Holter monitoring and/or electrocardiograms, and thyroid ultrasonography to assess thyroid size were performed serially.

RESULTS: Twenty-eight patients participated. Median goiter size was 20 mL (range, 7-79 mL). After each rhTSH dose, the radioiodine uptake approximately doubled at each time point compared with baseline uptake. Small rises in serum thyroxine and triiodothyronine were seen in some patients, especially after 0.3-mg rhTSH, and mild symptoms of hyperthyroidism developed in several patients. Flow-volume loop showed transient, mild asymptomatic worsening in 1 patient with a 35.2 mL goiter, although thyroid volume measurements were unchanged. Minor electrocardiogram and/or Holter changes were seen in several patients.

CONCLUSIONS: A flat dose-response curve exists over the range of rhTSH doses tested, with an approximate doubling of thyroid RAIU. All patients tolerated rhTSH well, but the rise in thyroid hormone levels and adverse effects after rhTSH doses of 0.1 mg or higher theoretically might not be well tolerated in older or sicker patients and appear unjustified given the lack of a greater rise in RAIU compared with the 0.03-mg dose. Future studies evaluating rhTSH doses less than 0.1 mg in patients with multinodular goiter are justified.