Cushing's Disease

Aka: Cushing's Disease, Cushing's Syndrome, Cushing Disease, Cushing Syndrome

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II. Etiologies

  1. Iatrogenic
    1. Steroid therapy (most common cause)
  2. Central Cause
    1. Pituitary Adenoma
  3. Adrenal Cause
    1. Adrenal Adenoma
    2. Adrenal Hyperplasia
    3. Adrenal Malignancy (15%)
  4. Ectopic Source
    1. Malignancy (Small Cell Carcinoma of the lung: 15%)

III. Symptoms

  1. Mood changes (depression and euphoria)
  2. Easy Bruising
  3. Weakness
  4. Weight gain
  5. Amenorrhea
  6. Back pain

IV. Signs

  1. Truncal Obesity (90%)
  2. Hypertension (85% when Cushing Disease is caused by tumors, 20% when iatrogenic)
  3. Glucose Intolerance (80%)
  4. Hirsutism (70%)
  5. Wide, purple abdominal and thigh striae (65%)
  6. Osteoporosis (55%)
  7. Moon facies
  8. Buffalo hump (Thoracic kyphosis)
  9. Myopathy
  10. Plethoric face
  11. Supraclavicular fat pad development
  12. Hypertrichosis
  13. Peripheral Edema
  14. Hypertension

V. Labs

  1. Screening Test
    1. 24-hour Urinary free cortisol level (preferred)
      1. Urine 17-Ketosteroid excretion
      2. Urine 17-Hydroxysteroid excretion
    2. Serum Cortisol
    3. Low dose Dexamethasone Suppression Test
      1. Dexamethasone 1 mg at 11pm
      2. Plasma Cortisol in following 8 AM
    4. Night-time Salivary Cortisol testing
  2. Distinguish between pituitary, adrenal or ectopic cause
    1. Plasma ACTH
    2. High dose Dexamethasone Suppression Test (8 mg)

VI. Radiology

  1. CT or MRI Cone down Sella Turcica
    1. Pituitary Adenoma
  2. CT Abdomen
    1. Adrenal Adenoma

VII. Management

  1. Exogenous Cushing Syndrome (Iatrogenic Cushing Syndrome, most common cause)
    1. Stop Corticosteroids or decrease dose
    2. Change steroid dosing to every other day with drug holiday
  2. Endogenous Cushing Syndrome
    1. Surgically excise adenoma (in pituitary or adrenal)

VIII. References

  1. Magiakou (2006) Best Pract Res Clin Endocrinol Metab 20(3): 467-82 [PubMed]
  2. Orth (1995) N Engl J Med 332:791-803 [PubMed]

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