Recent advances in the evaluation of Cushing's syndrome

The diagnostic evaluation of Cushing's syndrome has been the subject of review and debate ever since its original description by Harvey Cushing in 1932 [1]. In the past 5 years, several new tests have been introduced into the diagnostic algorithm for patients with suspected Cushing's syndrome. In the first section, dealing with the diagnosis of Cushing's syndrome, we will examine several recent noninvasive tests that have been proposed to distinguish Cushing's syndrome from pseudo-Cushing states. These include the dexamethasone-suppressed corticotropin-releasing hormone test [2], diurnal sampling of serum cortisol levels [3], and measurement of central CRH levels [7]. The second section discusses pitfalls in determining whether or not the excess cortisol secretion in Cushing's syndrome is ACTH dependent. In the third section, the use of invasive tests to distinguish pituitary-dependent Cushing's disease from the ectopic ACTH syndrome, including high jugular [5], inferior petrosal sinus sampling [6], and cavernous sinus sampling [7], will be discussed. The fourth section reviews the efficacy of sampling and imaging procedures for the intrapituitary localization of pituitary adenomas. Finally, we compare various imaging procedures for localizing ectopic ACTH- secreting tumors. In addition to evaluating the efficacy of these new tests, we recommend an appropriate place for each of these evaluations in the diagnostic algorithm of Cushing's syndrome and comment on the cost-effective work-up of the patient with Cushing's syndrome with particular attention to the unusual problems of cyclic Cushing's syndrome, CRH-dependent corticotroph hyperplasia, and nodular adrenal disease.