What laboratory tests are recommended for diagnosing Cushing's syndrome and hyperaldosteronism?

Laboratory Tests for Diagnosing Cushing's Syndrome and Hyperaldosteronism

For diagnosing Cushing's syndrome and hyperaldosteronism, the recommended initial laboratory tests are 1 mg overnight dexamethasone suppression test for Cushing's syndrome and plasma aldosterone/renin ratio for hyperaldosteronism. 1

Cushing's Syndrome Diagnostic Tests

Initial Screening Tests

• 1 mg overnight dexamethasone suppression test (DST)

  • Patient takes 1 mg dexamethasone at 11:00 PM
  • Blood drawn for cortisol at 8:00 AM the next morning
  • Interpretation:
    • Normal: Cortisol <1.8 μg/dL (50 nmol/L) excludes Cushing's
    • 51-138 nmol/L: Possible autonomous cortisol secretion

    • 138 nmol/L: Evidence of cortisol hypersecretion 1, 2

• Late-night salivary cortisol (LNSC)

  • Collect at bedtime (22:00-24:00)
  • Perform ≥2 tests on consecutive days
  • Highly specific test that assesses loss of normal circadian rhythm 1

• 24-hour urinary free cortisol (UFC)

  • Average of 2-3 collections recommended
  • Elevated levels indicate Cushing's syndrome 1

Confirmatory Tests

• ACTH level measurement

  • To differentiate ACTH-dependent from ACTH-independent Cushing's
  • Low ACTH suggests adrenal cause
  • Normal/high ACTH suggests pituitary or ectopic source 1

• Dexamethasone-CRH test

  • For differentiating true Cushing's from pseudo-Cushing's
  • CRH-stimulated cortisol >87 nmol/L after dexamethasone suppression strongly suggests true Cushing's 1, 3

Hyperaldosteronism Diagnostic Tests

Initial Screening Test

• Plasma aldosterone/renin ratio (ARR)

  • Collect in morning after patient has been upright for 2 hours and seated for 5-15 minutes
  • Ratio >30 suggests primary hyperaldosteronism
  • Patient should be potassium-replete and off interfering medications 1

• Serum electrolytes

  • Check for hypokalemia and mild hypernatremia
  • Excessive aldosterone causes sodium retention and potassium excretion 1

Confirmatory Tests

• Saline suppression test or salt loading test

  • Confirms diagnosis when ARR is positive
  • Failure to suppress aldosterone with volume expansion confirms diagnosis 1

• 24-hour urinary aldosterone measurement

  • Particularly with salt loading to confirm diagnosis 1

Important Considerations

For Cushing's Testing

• Withdraw interfering medications when possible
• Measure dexamethasone level along with cortisol after DST to improve test interpretation
• Consider cyclic Cushing's if initial tests are negative but clinical suspicion remains high 1
• False positives can occur with:
  • Severe obesity
  • Uncontrolled diabetes
  • Pregnancy
  • Depression
  • Alcoholism 1

For Hyperaldosteronism Testing

• Medication effects on ARR:

  • Beta-blockers, NSAIDs, and clonidine can cause false positives
  • ACE inhibitors, ARBs, and diuretics can cause false negatives
  • Ideally withdraw these medications 2-4 weeks before testing 1

• Potassium status:

  • Hypokalemia lowers aldosterone and can cause false negatives
  • Correct hypokalemia before testing 1

Common Pitfalls to Avoid

1. Not standardizing collection conditions for ARR
2. Testing during acute illness or stress
3. Not considering medication effects on test results
4. Relying on a single test rather than using multiple complementary tests
5. Not confirming positive screening tests with confirmatory tests 1

Diagnostic Algorithm

1. For Cushing's syndrome:

   • Start with 1 mg DST and/or late-night salivary cortisol
   • If positive, confirm with 24-hour UFC
   • Measure ACTH to determine source (adrenal vs. pituitary/ectopic)
   • Use imaging after biochemical confirmation 1

2. For hyperaldosteronism:

   • Start with ARR and electrolytes in patients with hypertension
   • If ARR >30, proceed to confirmatory testing
   • Use adrenal imaging and possibly adrenal vein sampling to determine if unilateral or bilateral disease 1

Remember that proper test interpretation requires consideration of clinical context, medication use, and potential confounding conditions to avoid misdiagnosis.