Diagnostic Workup for Congenital Adrenal Hyperplasia in Adults
Initial Clinical Assessment
- The American College of Cardiology recommends screening for clinical manifestations of CAH including hypertension with hypokalemia, virilization in females, or incomplete masculinization in males and primary amenorrhea in females 1
- Evaluate for signs of cortisol deficiency including fatigue, weakness, weight loss, and hypotension, as recommended by the Journal of Internal Medicine 2
Laboratory Testing
- First-line testing should include measurement of serum electrolytes, morning cortisol, and ACTH levels to assess for adrenal insufficiency, according to the Journal of Internal Medicine 2, 3
- Perform ACTH stimulation test to evaluate cortisol response, with a normal response being cortisol exceeding 550 nmol/L at one of the timepoints, as recommended by the Journal of Internal Medicine 3
- Measure specific adrenal steroid precursors based on suspected enzyme deficiency, such as elevated deoxycorticosterone (DOC), 11-deoxycortisol, and androgens for 11-beta-hydroxylase deficiency, as recommended by the American College of Cardiology 1
Genetic Testing
- Perform genetic analysis of steroidogenic genes, including CYP21A2 gene testing for 21-hydroxylase deficiency, as recommended by the Journal of Internal Medicine 2
Imaging Studies
- Perform adrenal CT scan to evaluate for adrenal hyperplasia, rule out adrenal tumors, and check for adrenal calcifications, as recommended by the Journal of Internal Medicine and the American College of Cardiology 2, 3, 5
Differential Diagnosis
- Rule out other causes of primary adrenal insufficiency, such as autoimmune adrenalitis, adrenal hemorrhage or infarction, infiltrative disorders, and infections, as recommended by the Journal of Internal Medicine 2, 3
- In males with hypogonadism, consider X-linked adrenoleukodystrophy by measuring very long-chain fatty acids (VLCFA), as recommended by the Journal of Internal Medicine 2, 3
Management Implications
- Once diagnosed, adults with CAH require lifelong hormone replacement therapy with glucocorticoids and often mineralocorticoids, as recommended by the Journal of Internal Medicine 2