LAUSR

Endogenous Cushing syndrome is a rare endocrine disorder with serious health implications. The July 2018 Endocrinology and Metabolism Clinics of North America issue is an update on pathogenesis, diagnosis, management, and prognosis of this challenging condition. The articles were written with a clinical focus by a group of international experts in the field. A review on Cushing syndrome is timely as more patients are screened for hypercortisolism in context of increased prevalence of obesity, diabetes, and adrenal incidentaloma. Differentiation of mild Cushing syndrome from reactive hypercortisolism (or “pseudo-Cushing”) entails a thorough understanding of the available tests and their caveats. Substantial evidence has accumulated regarding outcomes of patients with “subclinical Cushing syndrome.” Several factors must be considered when identifying patients who might benefit from surgical removal of adrenal incidentalomas. Children and pregnant women are rarely affected by Cushing syndrome; however, these patient categories pose urgent and unique diagnostic and management problems. Cushing syndrome is classified in two main categories: ACTH dependent (Cushing disease and ectopic Cushing syndrome) and ACTH independent. Syndromic presentation of hypercortisolism is infrequent and may affect patients with McCune-Albright syndrome, Carney complex, and multiple endocrine neoplasia. Recognizing these entities has implications for clinical management and genetic counseling. In addition, Cushing disease can rarely occur in the setting of familial isolated pituitary adenomas. Recent studies point to germline loss-of-function mutations in the aryl hydrocarbon receptor interacting protein gene as the most frequent abnormality in these cases. Cushing disease, the most frequent type of Cushing syndrome, is caused by an ACTH-secreting pituitary adenoma. Transsphenoidal adenomectomy by an expert neurosurgeon leads to biochemical remission in most cases, but carries a substantial risk of recurrence. Additional treatments with curative intent include pituitary