What is the diagnostic workup for congenital adrenal hyperplasia (CAH) in adults?

Diagnostic Workup for Congenital Adrenal Hyperplasia in Adults

The diagnostic workup for congenital adrenal hyperplasia (CAH) in adults should include specific hormone testing, genetic analysis, and imaging studies to confirm the diagnosis and determine the subtype.

Initial Clinical Assessment

• Screen for clinical manifestations of CAH including hypertension with hypokalemia, virilization in females (11-beta-hydroxylase deficiency), or incomplete masculinization in males and primary amenorrhea in females (17-alpha-hydroxylase deficiency) 1
• Evaluate for signs of cortisol deficiency including fatigue, weakness, weight loss, and hypotension 1
• Assess for signs of androgen excess in females: hirsutism, acne, menstrual irregularities, or infertility 2
• Check for short stature, which is common in adults with undiagnosed CAH 2
• Screen for metabolic complications including insulin resistance and obesity, which are frequently present in adults with CAH 2

Laboratory Testing

• First-line testing should include measurement of serum electrolytes, morning cortisol, and ACTH levels to assess for adrenal insufficiency 1
• Perform ACTH stimulation test (cosyntropin/synacthen test) to evaluate cortisol response:
  • Administer 0.25 mg cosyntropin intramuscularly or intravenously
  • Measure serum cortisol at baseline, 30 minutes, and 60 minutes
  • Normal response: cortisol should exceed 550 nmol/L at one of these timepoints 1
• Measure specific adrenal steroid precursors based on suspected enzyme deficiency:
  • For 11-beta-hydroxylase deficiency: measure elevated deoxycorticosterone (DOC), 11-deoxycortisol, and androgens 1
  • For 17-alpha-hydroxylase deficiency: measure decreased androgens and estrogen, elevated deoxycorticosterone and corticosterone 1
• Evaluate aldosterone and renin levels, which are typically low or normal in CAH 1

Genetic Testing

• Perform genetic analysis of steroidogenic genes:
  • CYP21A2 gene testing for 21-hydroxylase deficiency (most common form) 1, 2
  • CYP11B1 gene for 11-beta-hydroxylase deficiency 3
  • CYP17A1 gene for 17-alpha-hydroxylase deficiency 3
• Consider comprehensive panel testing for all steroidogenic enzyme defects if clinical picture is unclear 2

Imaging Studies

• Perform adrenal CT scan to:
  • Evaluate for adrenal hyperplasia
  • Rule out adrenal tumors or other causes of symptoms
  • Check for adrenal calcifications (which may indicate other conditions like tuberculosis) 1
• Consider pelvic ultrasound in females to evaluate for polycystic ovaries and reproductive tract abnormalities 3

Differential Diagnosis

• Rule out other causes of primary adrenal insufficiency:
  • Autoimmune adrenalitis (check for 21-hydroxylase antibodies) 1
  • Adrenal hemorrhage or infarction 1
  • Infiltrative disorders (amyloidosis, hemochromatosis) 1
  • Infections (tuberculosis, fungal infections) 1
• In males with hypogonadism, consider X-linked adrenoleukodystrophy by measuring very long-chain fatty acids (VLCFA) 1

Special Considerations

• Adults with non-classic CAH may present with milder symptoms and partial enzyme deficiencies 4, 5
• Fertility issues are common in adults with CAH and should be assessed 3
• Metabolic complications including obesity, insulin resistance, and cardiovascular risk factors should be evaluated 2
• Bone mineral density assessment is recommended due to increased risk of osteopenia/osteoporosis 3

Management Implications

• Once diagnosed, adults with CAH require lifelong hormone replacement therapy with glucocorticoids and often mineralocorticoids 1
• Regular monitoring of metabolic parameters, blood pressure, and bone health is essential 2, 3
• Fertility treatment may be necessary in both males and females 3

By following this systematic diagnostic approach, clinicians can accurately diagnose CAH in adults, determine the specific enzyme deficiency, and initiate appropriate management to improve clinical outcomes and quality of life.