Maester’s Collection: Cushing Syndrome

  • Central obesity, arterial hypertension, proximal muscle weakness, diabetes, oligomenorrhea, hirsutism, thin skin, and ecchymosis
  • Today, obesity is common. Anti-androgenic effects of Cushing syndrome can help differentiate it from obesity
    • +LR thin skin 112
    • +LR osteopenia 18
    • +LR ecchymoses 4
    • All 3 have a specificity of 95%
  • Prevalence of Cushing in obese/metabolic type patients 0.2%
    • 24,000 cases of Cushing/12 million patients with metabolic syndrome = 0.2%
  • 24 hour urinary free cortisol
    • 2-forms: 1) unbound to protein or 2) cortisol unconjugated to sulfuric or hyaluronic acid
    • Unbound cortisol is filtered and reabsorbed. 3% remains in urine.
    • Should measure 24-hour urine creatinine with cortisol to ensure adequate collection
      • Repeat if creatinine is less than 1.5g/day for men and 1g/day in women
    • 24-hour urine cortisol > 62mg/day has +LR 11
  • Dexamethasone Suppression test is used to differentiate ACTH dependent from ACTH independent Cushing syndrome.
    • This is now done by directly measuring ACTH levels
    • Should not be used to diagnose or screen for Cushing syndrome
      • Obese patients with depression will fail to suppress cortisol in response to dexamethasone challenge
  • For Cushingoid exam, but low or zero urinary free cortisol and suppressed ACTH levels suggests exogenous steroid and should prompt a review of medications.
  • ACTH-dependent Cushing syndrome can be due to pituitary secretion from an adenoma or ectopic secretion from a malignant source – typically in the chest.
  • Some experts recommend always doing petrosal sinus sampling due to the high prevalence of non-functioning pituitary adenomas and mortality associated with surgery. Some series report the prevalence of asymptomatic pituitary adenomas as high as 15-40%. Mortality associated with transsphenoidal micro-adenectomy is 1%.
  • ACTH-independent Cushing syndrome is usually caused by an adrenal neoplasm.
    • Characteristics of benign tumors: small (<5cm), <10 Hounsfield units, and have > 60% contrast washout at 15 minutes.
      • Benign tumors can be treated laparoscopically, while malignant tumors typically are resected with an open technique.
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