Ectopic cushing's syndrome

Abstract

Ectopic Cushing's syndrome refers to endogenous hypercortisolism originating from adrenal stimulation by ACTH produced inappropriately by a variety of extrapituitary tumors. On very rare occasions ectopic Cushing's syndrome is due to pituitary ACTH secretion driven by ectopic CRH secretion. Although the first extrapituitary tumor associated with hypercortisolism was reported as early as in 1928, it was in 1962 when ectopic Cushing's syndrome was characterized as a disorder of ACTH production by neoplastic cells [44].In the following years it became evident that there are two types of ectopic ACTH syndrome (EAS). One is associated with overt malignancies, the prototype being small-cell lung cancer (SCLC) and the other with more indolent neoplasms, represented mainly by bronchial and other carcinoid tumors.Although EAS is rare, it is the underlying cause in a substantial proportion (10-20%) of patients presenting with ACTHdependent Cushing's syndrome [57, 86]. Differentiation of ectopic ACTH secretion from "eutopic" overproduction by pituitary corticotroph adenomas is of paramount importance and represents,on many occasions, one of the most challenging problems in clinical endocrinology. In recent years efforts have been directed to understanding the pathophysiology of EAS and developing effective diagnostic tests to differentiate between EAS and Cushing's disease. Our current knowledge related to these issues is summarized in this chapter.