Cushing Syndrome

Definitions

Cushing syndrome: Elevated cortisol levels from any cause (exogenous or endogenous, ACTH-dependent or independent)

Cushing disease: Hypercortisolism specifically due to an ACTH-secreting pituitary adenoma

Signs/Symptoms

• Hypertension
• Hyperglycemia
• Abdominal striae
• Lipid re-distribution
  • Central obesity
  • “Moon” facies
  • “Buffalo hump” on back of neck
• Fatigue/weakness

Workup

Management:

Cushing’s Disease (ACTH-secreting pituitary adenoma) ₍₁₎

1st Line

• Surgical resection (works in ~2/3 of patients) is first line

2nd Line

• Pituitary radiotherapy (may induce pituitary insufficiency)
• Adrenal surgery (induces adrenal insufficiency)
• Medical therapy
  • Ketoconazole (inhibits steroid production) is the most commonly used drug
  • Mifepristone (glucocorticoid receptor antagonist) mainly for glucose intolerance
  • Cabergoline (dopamine agonist)
  • Pasireotide (somatostatin analog)

Adrenal hyperplasia/tumors

• Referral for adrenalectomy

Ectopic ACTH production ₍₂₎

• Tumor excision
• Medical therapy if surgery is not possible or if the source of ACTH secretion is unknown
  • Metyrapone, mitotane, ketoconazole, or etomidate (steroidogenesis inhibitors)

References:

1. Pivonello, R., De Leo, M., Cozzolino, A., & Colao, A. (2015, August). The treatment of cushing’s disease. Retrieved March 31, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523083/
2. Sakihara, S., Kageyama, K., Yamagata, S., Terui, K., Daimon, M., & Suda, T. (2014). A case of ectopic acth syndrome treated with intermittent administration of dopamine agonists. Retrieved March 31, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3965275/