Pathology of Adrenocorticotropic Hormone Excess

Adrenocorticotropic hormone (ACTH) excess may give rise to severe clinical symp-toms and marked laboratory alterations that, if not properly treated, can lead to irre-versible organ damage and patient death. This issue of Endocrinology Rounds presents an overview of the causes and pathology of ACTH hypersecretion, which is generally associ-ated with Cushing’s disease. The most common morphologic abnormality associated with this disorder is a basophilic microadenoma of the pituitary gland, accompanied by Crooke’s hyaline change in the cytoplasm of nontumourous corticotrophs. Tumour cells exhibit cytoplasmic PAS positivity and are immunoreactive for ACTH and related proopio-melanocortin (POMC)-derived peptides. Other tumour variants include chromophobic macroadenomas and Crooke’s cell adenomas. Corticotroph carcinomas are rare and gen-erally diagnosed only when cerebrospinal and/or systemic metastases are documented. Patients with Nelson’s syndrome usually have rapidly growing, invasive, aggressive corti-cotroph adenomas. Cushing’s disease may rarely be the result of a nodular or diffuse corti-cotroph hyperplasia. ACTH oversecretion may also be caused by ectopic ACTH and/or corticotropin-releasing hormone (CRH) production by various tumours, as well as smal