Pathophysiology and diagnosis of Cushing's syndrome

Abstract

Prolonged exposure of every tissue in the body to an excess of cortisol produces Cushing's syndrome. Endogenous causes of Cushing's syndrome are ACTH-dependent, including Cushing's disease, ectopic ACTH-producing tumors. CRH-producing tumors, and ACTH-independent Cushing's syndrome, including cortisol-producing adrenal benign or malignant tumors, and rare micronodular adrenal hyperplasia. In Japan the incidence of ACTH-dependent Cushing's syndrome due to endogenous causes is about 60%, in which autonomous pituitary ACTH secretion is responsible for 95%, and the rest are ectopic ACTH-producing tumors. Cortisol-secreting tumors are responsible for about 40% of endogenous causes, in which benign adenoma is 90% and adrenocortical carcinoma is 10%. The first step for the diagnosis of Cushing's syndrome is to demonstrate the presence of hypercortisolism biochemically by determining 24-hour urinary free cortisol excretion and low-dose dexamethasone suppression test. The next step is to identify the precise etiologic causes. To differentiate Cushing's syndrome, the most important procedures are dynamic endocrine tests to check the integrity of hypothalamic-pituitary-adrenal function by high dose dexamethasone suppression test, CRH test arid measurement of steroid hormone profile. Imaging techniques can help to determine the etiology of Cushing's syndrome.