Cushing Syndrome

Snapshot

  •  A 42-year-old obese woman who does not smoke presents with diastolic hypertension and menstrual irregularities. Physical exam shows a full, plethoric-appearing face, increased facial hair, truncal obesity, and purple striae around the abdomen. Scattered echymoses are present over the entire body. Labs show a Hgb of 18 g/dL and a WBC of 18,000/mm^3. The leukocyte differential shows an absolute neutrophillic leukocytosis. CXR is normal.

Introduction

  • A condition that refers to the manifestations of hypercortisolism
    • results in hyperplasia of the adrenal cortex 
      • specifically the fasiculata
  • There are several types
    • iatrogenic Cushing’s
      • patients taking steroids is the most common cause of Cushing’s syndrome
    • pituitary adenoma (Cushing’s disease)
      • most common pathogenic cause (70%)
      • majority of adenomas are benign
      • cause bilateral hyperplasia of the adrenal glands
        • associated increase in conversion of norepinephrine to epinephrine in medulla 
          • enzyme involved is phenylethanolamine n-methyltransferase
    • adrenal Cushing’s 
      • adenoma of the adrenals
    • ectopic Cushing’s
      • ectopic ACTH secretion
      • extremely high ACTH
      • most commonly from small cell carcinoma of the lung
  • less commonly thymic cancer

Presentation

  • Symptoms
    • depression and psychological changes
    • oligomenorrhea
    • growth retardation
    • weakness
      • catabolism of muscle for gluconeogenesis
    • symptoms of diabetes (polydipsia, polyuria, and dysuria)
  • Physical exam
    • diastolic hypertension
    • central obesity
    • muscle wasting
    • thin skin that easily bruises/purple abdominal striae
      • due to weakening of collagen
    • hirsutism
    • moon facies
  • buffalo hump

Evaluation

  • Labs
    • hyperglycemia
      • cortisol is gluconeogenic
    • hypokalemia
      • at high concentrations cortisol can have partial activity at the aldosterone receptor
    • screen for 24-hour free urinary cortisol as well as a serum cortisol level
      • high positive and negative predictive value
    • serum ACTH to localize lesion  
      • iatrogenic
        • ↓ ACTH
      • pituitary
        • ↑ ACTH
      • adrenal
        • ↓ ACTH
      • ectopic
        • ↑ ACTH
    • if ACTH is high, then use high dose dexamethasone suppression test 
      • pituitary
        • ↓ cortisol production (i.e. production is suppressible) 
      • ectopic
        • no change in cortisol (i.e. production is NOT suppressible)