The clinical conditions associated with hypercortisolism can be divided into two broad categories: Cushing's syndrome and Pseudo-Cushing' s syndrome. Cushing ' s syndrome is hypercortisolism leading to a predictable pattern of clinical sequelae, including obesity, hypertension, glucose intolerance, amenorrhea, osteoporosis, and immune compromise. Pseudo-cushing's syndrome is hypercortisolism in the absence of these clinical manifestations of glucocorticoid excess. With the ability to make the diagnosis of Cushing's syndrome at progressively earlier points in the clinical course, differentiating Cushing's syndrome from pseudo- Cushing's syndrome has become an important clinical issue. Currently, there is no easy way to do this, short of waiting to see if the clinical manifestations of Cushing's syndrome develop in the patient.The common causes of pseudo-Cushing's syndrome include depression, alcoholism, and caloric or physical stress. Recent data suggest that Cushing's syndrome is always CRH independent, while pseudo- Cushing's syndrome is always CRH dependent. This application is based on a hypothesis proposing that two groups can be separated based upon the plasma- adrenocorticocotropic hormone (ACTH) response to an opiate antagonist such as naloxone. Blocking endogenous opiate tone has been shown to enhance ACTH secretion in several animal species. Hence the hypothesis that Naloxone will stimulate ACTH release when CRH are high, and will not affect ACTH secretion when blood level of CRH are low, a strategy likely to separate patients with Cushing's syndrome from those with pseudo-Cushing's syndrome. The results of this study could provide further evidence for a direct role of hypothalamic CRH in the three major disorders of pseudo- Cushing's syndrome and yield new insights into the pathogenesis of these disorders. The investigators also propose to study the recovery of the hypothalamic pituitary-adrenal-axis function following suppression by endogenous or exogenous hypercortisolism.
| Orth, D N (1995) Cushing's syndrome. N Engl J Med 332:791-803 |
| Orth, D N (1994) The Cushing syndrome: quest for the Holy Grail. Ann Intern Med 121:377-8 |
