The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline

Abstract

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.

Figure 1

Algorithm for testing patients suspected of having Cushing's syndrome (CS). All statements are recommendations except for those prefaced by suggest. Diagnostic criteria that suggest Cushing's syndrome are UFC greater than the normal range for the assay, serum cortisol greater than 1.8 μg/dl (50 nmol/liter) after 1 mg dexamethasone (1-mg DST), and late-night salivary cortisol greater than 145 ng/dl (4 nmol/liter).