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Cushings syndrome

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Cushing's syndrome refers to the set of clinical features resulting from persistently and inappropriately elevated levels of glucocorticoid. Usually the condition is iatrogenic.

  • estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually (1)

Spontaneous Cushing's syndrome is rare, more common in females, and in about two-thirds of cases, due to Cushing's disease, that is due to pituitary-dependent adrenal hyperplasia

  • can be broadly divided into adrenocorticotropic hormone (ACTH)-dependent (approximately 80%; Cushing's disease (CD), ectopic ACTH secreting tumors, corticotropin-releasing hormone (CRH)-secreting tumors) and ACTH-independent (20%; adrenal tumor, carcinoma, and macronodular hyperplasia (AIMAH)) (2)
    • CD refers to a rare disorder caused by pituitary corticotroph tumors and represents the most common cause (nearly 70% in adults) of endogenous CS

Identification of the cause of the condition is essential to effective management.

Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use

  • screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose
  • plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels)
  • pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism

Management of Cushing syndrome

  • surgical intervention to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers.
  • radiation therapy and bilateral adrenalectomy may be appropriate if patient does not respond to surgery and medical treatment (1)


  • Reincke M, Fleseriu M. Cushing Syndrome: A Review. JAMA. 2023;330(2):170–181. doi:10.1001/jama.2023.11305
  • Nishioka H, Yamada S. Cushing's Disease. J Clin Med. 2019 Nov 12;8(11):1951. doi: 10.3390/jcm8111951. PMID: 31726770; PMCID: PMC6912360.

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