Congenital Adrenal Hyperplasia - CAH

Diagnosis

Indications for Testing

• Ambiguous genitalia or unexplainable electrolyte results in infancy
• Premature sexual development in older children
• Hirsutism and irregular menses in adult females

Laboratory Testing

• Initial testing
  • 17-OHP
    • If elevated, perform ACTH stimulation (cosyntropin)
      • Often unnecessary when there is marked elevation of 17-OHP
      • 17-OHP remains increased after stimulation in classic CAH
    • If nonclassic form is suspected in adult female, obtain 17-OHP at 0800 hours and during follicular phase of menstrual cycle
    • Further evaluation should include assessment of salt wasting
      • Serum sodium, potassium, and renin activity: expect hyponatremia, hyperkalemia, and increased renin in classic 21-hydroxylase deficiency CAH
• Secondary testing
  • Adrenal steroid quantitative panel: if ACTH stimulation is abnormal or if a marked elevation of 17-OHP is noted
    • 21-hydroxylase deficiency
      • Characterized by markedly elevated plasma 17-OHP
    • 11-beta-hydroxylase deficiency
      • Indicated by increased 11-deoxycorticosterone and 11-deoxycortisol levels
    • 17-hydroxylase (17-OH) deficiency
      • Characterized by increased pregnenolone, 11-deoxycorticosterone, and corticosterone, and decreased 17-hydroxypregnenolone (17-OH-pregnenolone)
    • 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency
      • Indicated by increased pregnenolone, 17-OH pregnenolone, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS)
• Testing in infants
  • Karyotyping to rule out chromosomal disorder
  • Pelvic ultrasonography to assess internal genital organs in females
  • Assess glucose, electrolytes, liver function, and blood gases in infants suspected of acute adrenal insufficiency

Screening

• Newborn screening for CAH in most states: 17-OHP
  • Threshold for positive tests is set relatively low to prevent missing true positives
  • False positives common in premature infants, who tend to have increased 17-OHP
    • Markedly increased 17-OHP confirms disease
      • Follow up positive results with ACTH stimulation in all infants
  • False negative may occur if maternal glucocorticoids are administered
• Prenatal diagnosis
  • Chorionic villus sampling or amniocentesis, 90-95% sensitive
  • Allows for prenatal treatment of disease through administration of maternal glucocorticoid​

Monitoring

• For assessment of glucocorticoid replacement
  • 17-OHP, androstenedione, and testosterone
    • Every 3 months during infancy and every 3-6 months thereafter
• For assessment of mineralocorticoid replacement
  • Blood pressure measurement
  • Plasma renin/renin activity
  • Aldosterone and potassium levels may also be helpful