Effects of Metoclopramide on Fasting-Induced TSH Suppression

Abstract

Short-term caloric deprivation leads to suppression of TSH secretion in healthy subjects, but the mechanism of this effect is unknown. Since dopamine inhibits TSH secretion at physiologic levels, increased endogenous dopamine activity may cause the TSH suppression observed during fasting. To test this hypothesis, 11 healthy subjects underwent four studies: (1) Baseline-subjects were allowed ad libitum food. (2) MCP-subjects were allowed ad libitum food and received iv metoclopramide (MCP) at 30 micrograms/kg/h over 48 h. (3) Fasting-subjects received no caloric intake for 56 h. (4) Fasting+MCP-subjects fasted for 56 h, and received iv MCP during the final 48 h of the study. Serum TSH levels were measured every 15 min during the final 24 h of each study, and a TRH stimulation test was performed at the conclusion of each study: 56 h of fasting decreased 24 h mean TSH levels and TSH pulse amplitude by 40%, with blunting of the TSH response to TRH. MCP infusions increased 24 h mean TSH levels and TSH pulse amplitude 26-34%, with no differences between the fasting and nonfasting studies. MCP infusions did not normalize TSH levels, TSH responses to TRH, or serum T3 levels during fasting. These data suggest that endogenous dopaminergic activity does not play a major role in fasting-induced TSH suppression in healthy subjects.

Mutations in IRS4 are associated with central hypothyroidism

“…42 Additionally, 56-hour fasting in healthy men and women was shown to decrease TSH responses to TRH by 43% below baseline responses. 43 In the present study, IRS4-mutated patients showed remarkably similar TSH baseline concentrations, 24-hour TSH secretion patterns and TRH test results. These data may suggest that the central downregulation of the HPT axis in patients with IRS4 mutations is mediated by subtle hypothalamic LEPR dysfunction.…”

Fatores Interferentes na Interpretação de Dosagens Laboratoriais no Diagnóstico de Hiper e Hipotireoidismo

“…Apesar disto, o tratamento crônico com drogas dopaminérgicas em pacientes criticamente enfermos não leva ao hipotireoidismo (69). O efeito inverso é observado com metoclopramida, um antagonista dopaminérgico, que aumenta a secreção de TSH (70). importante diminuição do T 3 e uma modesta elevação de T4, por uma marcada ação de inibição das enzimas 5'-desiodase do tipo 1 e 2 (37).…”

Central Nervous System Control of Thyrotropin Secretion during Sleep and Wakefulness

“…Dopaminergic or somatostatinergic factors are likely candidates for such changes as thyroid hormones with their long metabolic half-life are unlikely to act as rapid modulators of the system. Studies in fasting and nonfasting volunteers applying the dopamine receptor antagonist, metoclopramide, could not detect a difference in TSH increase in both groups and therefore modulation of dopamine should not be the mediating factor [31]. TRH infusion could not compensate the TSH reduction, thus arguing against an important role of TRH.…”