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Cushing's Syndrome: Rapid Evidence Review

David L. Maness, DO, MSS
Grant Studebaker, MD
Christopher M. Knight, MD

American Family Physician. 2024;110(3):270-280.

Author disclosure: No relevant financial relationships.

This clinical content conforms to AAFP criteria for CME.

Cushing's syndrome is a rare, multisystemic disease caused by chronic exposure to supraphysiologic levels of cortisol. Prolonged hypercortisolism is associated with significant multisystem morbidity and mortality and decreased quality of life. Diagnosis of Cushing's syndrome is often delayed by several years due to its insidiously progressive course, diverse clinical presentation, overlap of symptoms with many common conditions, and testing complexity. Exogenous glucocorticoid use must be excluded as the primary etiology. Excessive endogenous cortisol production can be caused by an overproduction of adrenocorticotropic hormone (ACTH) through pituitary tumors or ectopic sources (ACTH-dependent cases), or it can be caused by autonomous cortisol overproduction by the adrenal glands (ACTH-independent cases). The recommended diagnostic approach includes appropriate screening, confirmation of hypercortisolism, and determination of etiology. First-line treatment is surgical removal of the source of cortisol overproduction. Lifelong posttherapy monitoring is required to treat comorbidities and detect recurrence.

DAVID L. MANESS, DO, MSS, FAAFP, is a retired U.S. Army colonel and a professor at the University of Tennessee Family Medicine Residency Program, Jackson.

GRANT STUDEBAKER, MD, FAAFP, is the program director of the Department of Family Medicine at the University of Tennessee Health Science Center, Jackson.

CHRISTOPHER M. KNIGHT, MD, FAAFP, is an assistant professor in the Department of Family Medicine at the University of Tennessee Health Science Center, Jackson.

Address correspondence to David L. Maness, DO, MSS, at dmaness@uthsc.edu.

Author disclosure: No relevant financial relationships.

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