OBJECTIVES: I. Evaluate whether chronic hypercortisolemia is specifically toxic to hippocampal cells and causes structural reduction of hippocampal volume in patients with Cushing's syndrome.

II. Determine whether reduced hippocampal volume is associated with specific memory dysfunction.

III. Examine the relationships of adrenal androgen to hippocampal volume and memory dysfunction.

IV. Examine the reversibility of hippocampal structural changes and cognitive dysfunction after cortisol levels are normalized.

PROTOCOL OUTLINE: Patients undergo a psychiatric evaluation for mood and cognition during confirmation of diagnosis. Neuropsychologic exams include pencil and paper test and a cognitive assessment.

Endocrine studies include dexamethasone and corticotropin-releasing hormone stimulation tests. The hippocampal complex volume is assessed with coronal magnetic resonance imaging.

There is a follow-up 1 year after the initiation of treatment.

PROTOCOL ENTRY CRITERIA:

• Adults and teenagers with untreated, spontaneous active Cushing's syndrome
• Diagnosis verified at the University of Michigan Medical Center, including the following: Excessive cortisol secretion measured by urinary-free cortisol, cortisol secretion rate, and plasma cortisol level
• Lack of normal circadian cortisol secretion and failure to suppress following 2 mg of dexamethasone