Lack of evidence for pituitary thyrotroph down-regulation after 1 week of oral thyrotrophin-releasing hormone and metoclopramide under conditions of constant peripheral thyroid hormone levels

Department of Medicine, Wellington School of Medicine, New Zealand.

We investigated the pituitary thyrotrophin (TSH) response to repeated oral (non-pulsatile) thyrotrophin-releasing hormone (TRH) administration and potential modifying effects of dopamine antagonist treatment under conditions of constant peripheral thyroid hormone levels. In a randomized double-blind crossover trial, seven hypothyroid subjects, euthyroid on L-thyroxine, received 1 week each of oral TRH (40 mg, 12 hourly) plus metoclopramide (10 mg, 8 hourly) and TRH (40 mg, 12 hourly) plus placebo (one capsule, 8 hourly). At the beginning and end of each treatment period five samples of blood for estimation of serum TSH were taken over 1 h before ("baseline") and seven samples over 2 h after the treatment combination was given ("stimulated"). Serum free thyroxine, free triiodothyronine and prolactin levels also were measured. Mean log10 +/- SEM (log10 mIU/l) "baseline" serum levels TSH were -0.177 +/- 0.183 (median 0.345 mIU/l (untransformed); range (r) 0.03-10.11 mIU/l; first quartile (1q) 0.22 mIU/l; third quartile (3q) 2.48 mIU/l) before and 0.182 +/- 0.107 (median 1.385 mIU/l; r = 0.45-19.8 mIU/l; 1q = 0.9 mIU/l; 3q = 1.78 mIU/l) after 1 week of treatment (p < 0.02). There were no significant differences between oral TRH plus metoclopramide and oral TRH plus placebo. Peripheral thyroid hormone levels and the "stimulated" TSH response (expressed as area under curve after TRH and metoclopramide or placebo; min.log10 mIU/l) remained unchanged after 1 week. In the absence of changes in peripheral thyroid hormone levels, oral TRH over 1 week may not result in down-regulation of anterior pituitary thyrotrophs.2+ f2p4