How do you test the adrenal glands for dysfunction?

Testing the Adrenal Glands for Dysfunction

The cosyntropin (ACTH) stimulation test is the primary screening test for adrenal insufficiency, using 0.25 mg administered intravenously or intramuscularly, with serum cortisol measured at baseline, 30, and 60 minutes post-injection; a peak cortisol below 550 nmol/L (approximately 18-20 μg/dL) indicates adrenal insufficiency. 1, 2

Initial Clinical Assessment

When evaluating for adrenal dysfunction, first determine the clinical presentation:

• For suspected adrenal insufficiency: Look for orthostatic hypotension, hyperpigmentation (primary only), unexplained hypoglycemia, hyponatremia, hyperkalemia, fatigue, weight loss, and hypotension 1, 3
• For suspected hyperfunction: Assess for resistant hypertension, unprovoked hypokalemia, cushingoid features, or paroxysmal hypertensive episodes 1

Biochemical Testing Algorithm

For Adrenal Insufficiency

Step 1: Morning cortisol and ACTH measurement

• Morning cortisol <83 nmol/L (3 μg/dL) confirms adrenal insufficiency 3
• Morning cortisol >524 nmol/L (19 μg/dL) excludes adrenal insufficiency 3
• Intermediate values require dynamic testing 3

Step 2: Cosyntropin stimulation test (if cortisol intermediate)

• Administer 0.25 mg cosyntropin IV or IM 2
• Measure serum cortisol at 0,30, and 60 minutes 2
• Peak cortisol <550 nmol/L indicates adrenal insufficiency 1
• Critical: Stop glucocorticoids and spironolactone on the day of testing; discontinue long-acting glucocorticoids for a longer period beforehand 2

Step 3: Distinguish primary from secondary adrenal insufficiency

• Primary: High ACTH with low cortisol, plus hyponatremia and hyperkalemia 1
• Secondary: Low or normal ACTH with low cortisol 1, 4

For Primary Aldosteronism (Hyperfunction)

Step 1: Screening

• Measure aldosterone-to-renin ratio (ARR) under standardized conditions 1, 5
• Screen patients with resistant hypertension or unprovoked hypokalemia 1

Step 2: Confirmatory testing

• Fludrocortisone suppression test: failure to suppress plasma aldosterone after 4 days confirms diagnosis 1
• Alternative: saline infusion test or oral sodium loading 1, 5

Step 3: Localization

• CT or MRI imaging of adrenal glands 1, 6
• Critical caveat: Adrenal venous sampling is necessary to confirm lateralization, as CT alone leads to 25% unnecessary adrenalectomies due to non-functioning adenomas 1

For Pheochromocytoma

• Measure plasma or 24-hour urine metanephrines 1
• Must be excluded even in patients with known malignancy and suspected adrenal metastases 1

Etiologic Investigation After Diagnosis

For Primary Adrenal Insufficiency

First-line test: 21-hydroxylase autoantibodies (21OH-Ab)

• Positive result confirms autoimmune etiology (85% of cases in Western Europe) 1, 7
• If positive in young females, screen for APS-1 components: hypoparathyroidism, candidiasis, autoimmune hepatitis 1, 7

If 21OH-Ab negative:

• CT scan of adrenal glands to identify tumors, calcifications (tuberculosis), hemorrhage, or metastases 1
• In males: measure very long-chain fatty acids to screen for adrenoleukodystrophy 1
• Consider infectious workup: tuberculosis testing, HIV, fungal infections 1, 7
• Urine steroid profile and genetic testing for congenital adrenal hyperplasia 1

Imaging Modalities

CT scan is the primary imaging modality for adrenal masses 1, 6

• Use contrast washout analysis for indeterminate lesions 8
• MRI with chemical shift imaging can differentiate adenomas from other masses 6
• Isotopic techniques using radiolabeled cholesterol for functional assessment 1

Critical Pitfalls to Avoid

1. Never delay treatment for testing: If acute adrenal crisis is suspected, immediately administer IV hydrocortisone 100 mg and 0.9% saline; obtain cortisol and ACTH samples before treatment if possible, but do not delay therapy 1

2. Medication interference: Glucocorticoids, spironolactone, and estrogen-containing drugs falsely elevate cortisol levels; stop on day of testing (estrogen requires 4-6 weeks discontinuation) 2, 9

3. Imaging misinterpretation: Non-functioning adenomas and nodular hyperplasia can mimic functioning tumors; always correlate imaging with biochemical testing and consider adrenal venous sampling before surgery 1

4. Timing matters: The standard 250 μg ACTH test may miss early secondary adrenal insufficiency before adrenal atrophy occurs 3, 9

5. Cortisol-binding globulin effects: Conditions affecting CBG levels (pregnancy, estrogen therapy, liver disease) alter total cortisol measurements without affecting free cortisol 2, 9