Extra-Adrenal Action of Metyrapone upon Human Growth Hormone Secretion in Man

Extra-adrenal action of metyrapone (Metopiron, SU-4885, CIBA) upon HGH and ACTH secretion was investigated in four control subjects and three patients with hypoadrenalism. The administration of metyrapone caused the increase in plasma HGH not only in control subjects but also in three patients with hypoadrenalism. Plasma ACTH levels following the administration of metyrapone increased in a patient with Addison's disease and in an adrenalectomized patient due to Cushing's syndrome. Metyrapone did not cause the significant change in blood sugar levels during the test period. Plasma cortisol levels fell rapidly for 2 hr and reached a plateau and then increased at 4 hr after metyrapone administration in control subjects. In three patients with hypoadrenalism, plasma cortisol levels were low at resting time and became lower to an undetectable level after the administration. All subjects complained of side effects, such as gastric pain, fatigue etc. These findings demonstrate that there is an extra-adrenal action of metyrapone upon HGH secretion and suggest that metyrapone may stimulate directly the release of ACTH by the pituitary. Its action may not be mediated by glucose metabolism and cortisol metabolism, but may be a direct action on the central nervous system. Our experiment does not make clear whether a direct action of metyrapone on the central nervous system is a specific effect or not.