Transient goiter enlargement after administration of 0.3 mg of recombinant human thyrotropin in patients with benign nontoxic nodular goiter: a randomized, double-blind, crossover trial.

Abstract

Recombinant human (rh) TSH, in doses from 0.01 to 0.9 mg, has been used to augment the effect of radioiodine ((131)I) therapy in patients with a benign nontoxic nodular goiter. Transient thyroid enlargement and thyrotoxicosis may be seen following (131)I therapy. The aim of the study was to investigate whether rhTSH per se causes goiter enlargement, until now an issue evaluated only in healthy nongoitrous subjects. In random order, 10 patients with nontoxic nodular goiter [mean 39.8 +/- 20.5 (sd) ml] received either 0.3 mg rhTSH or isotonic saline in a double-blinded crossover design. Thyroid volume (by ultrasound) and function were closely monitored during the following 28 d. Saline injection did not affect thyroid function or size. After rhTSH, median serum TSH increased from baseline 0.97 mU/liter (range 0.39-1.56) to 37.0 mU/liter (range 18.5-55.0) at 24 h (P < 0.01), with a subsequent decline to subnormal levels at d 7. Mean free T(4) and free T(3) increased significantly from baseline to a maximum at 48 h. Twenty-four hours after rhTSH, the mean goiter volume was significantly increased by 9.8 +/- 2.3% (sem) (P = 0.01) and after 48 h by 24.0 +/- 5.1% (P = 0.002). The goiter enlargement had reverted at d 7. Nine patients had symptoms of hyperthyroidism and/or cervical compression after rhTSH, as opposed to one during placebo treatment (P < 0.02). A transient average goiter enlargement of up to 24% is seen after 0.3 mg rhTSH. This may lead to a significant cervical compression when used for augmentation of (131)I therapy in patients with goiter. The use of lower doses of rhTSH needs to be explored.