Evidence for ACTH-unrelated mechanisms in the regulation of cortisol secretion in man

In an attempt to elucidate the significance of ACTH independent mechanisms in the regulation of cortisol secretion in man, the dynamics of plasma ACTH and cortisol levels were studied in response to different stimuli. The cortisol response to small amounts of exogenous ACTH and to insulin induced hypoglycemia was preceded by an increase in ACTH levels appropriate to explain the increase in cortisol. In contrast, after administration of methamphetamine, there was an increase in cortisol levels in the absence of any changes in ACTH concentrations. Apparently, the methamphetamine induced cortisol secretion was not mediated by radioimmunoassayable ACTH. A diurnal rhythm was observed for the responses to hypoglycemia and to methamphetamine with larger cortisol responses in the evening as compared to the forenoon. These changes were not accompanied by parallel changes in the ACTH responses. From these differences, additional evidence is provided for the importance of ACTH independent mechanisms in the regulation of cortisol secretion.