Abnormal pituitary function during melancholia: Reduced α-melanocyte-stimulating hormone secretion and increased intact ACTH non-suppression

In order to investigate pituitary α-melanocyte-stimulating hormone (α-MSH), intact (1–39 structure) adrenocorticotropic hormone (ACTH), and adrenal cortisol secretion, we measured 8 a.m. plasma levels of those hormones before and after administration of 1 mg dexamethasone in 39 depressed inpatients and 10 healthy controls. We found a significantly lower baseline α-MSH secretion in melancholic patients as opposed to healthy controls. There were no significant relations between α-MSH secretion on the one hand and ACTH or cortisol secretion on the other. Dexamethasone did not affect the 8 a.m. α-MSH circulating levels. The post-dexamethasone intact ACTH and cortisol values were significantly higher in melancholics as compared with healthy, minor and simple major depressed subjects. ACTH non-suppression was defined as post-dexamethasone intact ACTH ⩾ 12 pg/ml. ACTH non-suppression was found to be more sensitive (70%) and specific (100%) for melancholia than cortisol non-suppression. By means of pathway analysis we have established that cortisol non-suppression during a severe depression is completely determined by an augmented ACTH escape from suppression by dexamethasone. It is concluded that the assay of post-dexamethasone intact ACTH could, in the future, replace post-dexamethasone cortisol determination.