Primary depression can be associated with substantial
hypercortisolism, thus prompting some researchers to suggest that depression shares pathophysiologic features with
Cushing's disease. Clinically, depression can be difficult or impossible to distinguish from mild or early
Cushing's disease that is associated with depressive features. The purpose of this study was to evaluate whether the pituitary-adrenal responses to ovine
corticotropin-releasing hormone could help to clarify the mechanism of
hypercortisolism in depression and in
Cushing's disease and to assist in the differential diagnosis of these disorders. As compared with controls (n = 34), depressed patients (
n = 30) had basal
hypercortisolism (P less than 0.001) that was associated with attenuated plasma
ACTH responses to ovine
corticotropin-releasing hormone (P less than 0.001). This indicates that in patients with depression, the corticotroph cell in the pituitary responds appropriately to the negative feedback of high
cortisol levels. In contrast, patients with
Cushing's disease (n = 29) had plasma
ACTH hyperresponsiveness to ovine
corticotropin-releasing hormone (P less than 0.001), despite basal
hypercortisolism (P less than 0.001), which indicates a gross impairment of the mechanism by which
cortisol exerts negative feedback on the pituitary. Less than 25 percent of the patients with depression or
Cushing's disease had peak
ACTH responses that overlapped. We conclude that the pathophysiologic features of
hypercortisolism in depression and
Cushing's disease are distinct in each of the disorders and that the ovine
corticotropin-releasing hormone stimulation test can be helpful in their differential diagnosis.