Metyrapone: an agent for melatonin as well as ACTH and cortisol secretion

The metyrapone-test was used to study the influence of pituitary-adrenal activity on the pineal function in man. We recorded in blood the circadian rhythmicity of melatonin, ACTH and cortisol and the excretion of melatonin, cortisol and Porter-Silber chromogens in urine before, during and after the administration of 750 mg metyrapone every 4 h during 24 h in two healthy volunteers and in two patients with asymptomatic, moderate hyperparathyroidism and a prolactin-secreting microadenoma, respectively. The present study confirmed our previous report on an increased excretion of melatonin per 24 h and per mmol creatinine during the administration of metyrapone. The excretory maximum preceded the maximal ACTH-adrenal response. Serum melatonin remained unchanged during the administration of metyrapone. A second finding was depressed serum melatonin the night after the test in the subjects with the most marked ACTH-cortisol response following the metyrapone-test indicating suppression of melatonin secretion when ACTH-cortisol secretions were increased. A third finding was a late increase in diuresis appearing the day after metyrapone-administration while glomerular filtration rates did not show significant alterations. Thus, it is shown that the metyrapone-induced cortisol inhibition stimulates both ACTH and melatonin secretion, while high ACTH and cortisol levels are accompanied by reduced S-melatonin levels.