Cushing's Disease

Question 1

What is Cushing’s disease?

Answer 1

• Hyper-cortisolism from a variety of causes
• Usually due to a corticotropin (ACTH)-producing benign pituitary tumor `(micro adenoma) (Cushing’s tumor)

Question 2

What causes Cushing’s disease?

Answer 2

• 90% of Cushing’s syndrome cases are non-iatrogenic
• 70% caused by benign pituitary micro adenomas
• 10-15% of cases caused by adrenal neoplasms
  
  • Women are affected more often than men
• 15% of cases caused by non-pituitary neoplasms, such as small cell lung cancer
• Iatrogenic: causes by excessive glucocorticoid administration, including prolonged/chronic use

Question 3

What are the subjective/physical exam findings associated with Cushing’s disease?

Answer 3

More common:

• Central Obesity
• Round (Moon) face
• Decreased libido
• Menstrual changes
• Hirsutism
• Hypertension
• Fragile, ecchymotic skin
• Lethargy/depression
• Buffalo hump – dorsal fat pad
• Abnormal glucose tolerance test

Less Common:

• Acne
• Proximal muscle atrophy
• Purple striae
• Backache
• Headache
• Osteopenia/Osteoporosis/Fractures
• Female balding
• EKG abnormalities/atherosclerosis

Question 4

How do you diagnose a patient with Cushing’s syndrome?

Answer 4

The diagnosis of Cushing’s Syndrome (CS) is established when at least 2 different first-line tests are unequivocally abnormal. Once the diagnosis is established, additional evaluation is done to identify the cause of the hypercortisolism.

Question 5

What are the 3 first line diagnostic tests to diagnose Cushing’s syndrome?

Answer 5

1. Late-night salivary cortisol (2 measurements must be abnormal for the test to be considered abnormal because the hypercortisolism in CS may be variable),
2. 24-hour urinary free cortisol (UFC) excretion (2 measurements), OR
3. Overnight 1 mg dexamethasone 1mg suppression test (DST)

Question 6

How is a Dexamethasone suppression test (DST) performed?

Answer 6

• Administer dexamethasone 1mg at 11pm, check serum cortisol at 8am the next day
  
  • Cortisol levels > 1.8 mcg/dL is suggestive of CS OR
  • Administer dexamethasone 2mg/day for 48 hours DST (0.5 mg po every 6 hours x 8 doses)
• On day 2, at least 2-6 hours after the last dose, obtain serum cortisol level, serum dexamethasone and ACTH level)
  
  • Cortisol levels greater than 1.8mcg/dL is suggestive of CS

Cannot be used as sole criterion for diagnosis- must be have at least one additional test to establish diagnosis

Question 7

How is a Urine Free Cortisol test conducted?

Answer 7

• Measures 24-hour urinary cortisol excretion
• UFC is usually less than 50 mcg/24 hours
• UFC greater than the normal range for the assay is considered diagnostic

Question 8

How do you manage patients with Cushing’s syndrome?

Answer 8

• Dependent upon etiology of hypercortisolism
• Treat underlying cause
• Resection of pituitary adenoma- Transphenoidal
• Surgical resection of adrenal neoplasms
• Discontinuation of exogenous glucocorticoids
• Manage fluid and electrolyte imbalances – restrict sodium intake
• Manage complications- i.e. osteoporosis
• Endocrinology referral