Cushing Disease and Cushing Syndrome



  • Cushing syndrome is defined as excessive glucocorticoid exposure from exogenous (steroid medications) or less commonly from endogenous sources (pituitary, adrenal, pulmonary, etc.).
  • Cushing disease is glucocorticoid excess due to excessive adrenocorticotropic hormone (ACTH) secretion from a pituitary tumor.
  • System(s) affected: endocrine/metabolic, musculoskeletal, skin/exocrine, cardiovascular; neuropsychiatric

Pediatric Considerations

  • Rare in infancy and childhood
  • The most common presenting symptom is lack of growth and weight gain.

Pregnancy Considerations
Pregnancy may exacerbate the disease.



  • An estimated 10 to 15 cases per million people are affected yearly.
  • Cushing disease most commonly affects adults aged 20 to 50 years and females.
  • 2–5% prevalence reported in difficult-to-control diabetics with obesity and hypertension (HTN)

Etiology and Pathophysiology

  • Cortisol is a steroid hormone produced by the zona fasciculata of the adrenal cortex. It is classically a catabolic hormone released during periods of stress. The excess causes increased free glucose, insulin resistance, and protein catabolism.
  • Prolonged glucocorticoid use such as in asthma and chronic obstructive pulmonary disease is the most common exogenous source.
  • Endogenous cause is either ACTH-dependent or ACTH-independent, as
    • ACTH is typically secreted by the pituitary which stimulates adrenal release. As such, release of ACTH from any source will result in increased cortisol level.


  • Multiple endocrine neoplasia (MEN)
  • McCune-Albright syndrome (mutation of GNAS1 gene)

Risk Factors

Prolonged use of corticosteroids

General Prevention

Avoid corticosteroid exposure.

Commonly Associated Conditions

Psychiatric disorders, diabetes, HTN, hypokalemia, infections, dyslipidemia, osteoporosis, and poor physical fitness

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