Dopaminergic modulation of circadian thyrotropin rhythms and thyroid hormone levels in euthyroid subjects

Basal TSH levels are known to rise during the evening, but the mechanism by which this rise occurs is poorly understood. The rise in TSH in response to dopamine (DA) receptor blockade with metoclopramide in the morning in normal subjects and hypothyroid patients has provided evidence for a tonic inhibitory role for DA in the control of TSH secretion. We have tested the hypothesis in normal, euthyroid volunteers (14 females, aged 20--40 yr; 12 males, aged 22--45 yr) that the nocturnal elevation of serum TSH levels might result from a reduction in DA action on the thyrotroph, in which case a reduced TSH response to metoclopramide would be expected. We found, however, that the TSH response to DA receptor blockade with metoclopramide (10 mg, iv) was significantly greater at 2300 h than at 1100 h [net incremental response over 120 min, 14.9 +/- 2.5 vs. 6.7 +/- 1.6 mU/liter (mean +/- SE); P < 0.001], indicating greater DA inhibition of TSH release at night. Thus, the nocturnal elevation of TSH is not due to decreased DA action on the thyrotroph; rather, increased DA tone is present and may limit the TSH response to other as yet unknown factors. Thyroid hormone levels also rose significantly after metoclopramide at both 1100 and 2300 h compared with control values after placebo [incremental difference (in nanomoles per liter) between 0 and 120 min values (mean +/- SE): 1100 h, T3, 0.24 +/- 0.09 vs. -0.05 +/- 0.08 (P < 0.02); T4, 19.4 +/- 6.1 vs. -1.8 +/- 2.5 (P < 0.01); 2300 h, T3 +/- 0.53 +/-0.07 vs. 0.04 +/- 0.07 (P < 0.01); T4 20.9 +/- 5.6 vs. 2.8 +/- 3.2 (P < 0.01)]. Incremental thyroid hormone and TSH responses to metoclopramide were directly related (T3 vs. TSH, r = 0.59 and P < 0.001; T4 vs. TSH, r = 0.41 and P < 0.01), suggesting that the thyroid hormone responses were mediated by TSH and illustrating the sensitivity of the thyroid gland to even small increases in endogenous TSH levels.