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The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

Program on Reproductive and Adult Endocrinology (L.K.N.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Neuroendocrine Unit/Massachusetts General Hospital (B.M.K.B.), Boston, Massachusetts 02114; Medical College of Wisconsin (J.W.F.), Milwaukee, Wisconsin 53226; University of Sheffield (J.N.-P.), Sheffield S102JF, United Kingdom; William Harvey Research Institute, Queen Mary, University of London (M.O.S.), London EC1M6BQ, United Kingdom; University of Birmingham (P.M.S.), Birmingham B15 2TT, United Kingdom; and Mayo Clinic (V.M.M.), Rochester, Minnesota 55905 Co-sponsoring Association: European Society of Endocrinology

Address all correspondence to: The Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, Maryland 20815. E-mail: govt-prof{at}endo.society.org. Address all reprint requests for orders of 101 and more to: Heather Edwards, Reprint Sales Specialist, Cadmus Professional Communications, 8621 Robert Fulton Drive, Columbia, Maryland 21046. E-mail: endoreprints{at}cadmus.com. Address all reprint requests for orders of 100 or less to Society Services. E-mail: societyservices{at}endo-society.org.

Objective: The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome.

Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.

Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments.

Conclusions: After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.