OBJECTIVES: I. Study the relationship between dysregulation of the
hypothalamic-pituitary-adrenal (HPA) axis and disorders of mood, vegetative function, and
cognition in patients with Cushing's disease.
II. Identify subgroups of patients with Cushing's disease who differ in the presence and
severity of the depressive syndrome, and uncover HPA axis dysregulation differences among
them using corticotropin-releasing hormone, metyrapone, and dexamethasone challenge testing.
PROTOCOL OUTLINE: All patients receive a psychiatric evaluation at baseline, as well as
assessments of plasma adrenocorticotropin, beta lipotropin, beta endorphin, and cortisol,
and urinary cortisol. Peptide and steroid assays are performed, alone and in response to
corticotropin-releasing hormone, metyrapone, and dexamethasone. Patients are given sleep
electroencephalograms at baseline and 1 year following treatment.
A weight maintenance diet is prescribed for all patients.
PROTOCOL ENTRY CRITERIA:
- Patients aged 20 to 60 with spontaneous active Cushing's syndrome
- At least 2 weeks since medication with psychoactive effects or influence on cortisol
metabolism by hepatic hydroxylating enzyme induction
- Antihypertensives allowed for severe hypertension
- No barbiturates
- No phenytoin