Congenital Adrenal Hyperplasia (CAH)

Pathophysiology & Presentation

• Most common cause: 21-hydroxylase deficiency (>90% of cases), leading to decreased cortisol and aldosterone, and increased androgens.
• Classic Salt-Wasting form: Presents at 1-2 weeks of life with adrenal crisis (hypotension, shock, vomiting, severe dehydration).
• Electrolyte derangement: Hyponatremia (Na < 130 mEq/L), Hyperkalemia (K > 6.0 mEq/L), metabolic acidosis, and hypoglycemia.
• Genital presentation: Virilized external genitalia in 46,XX females (ambiguous genitalia, clitoromegaly, labial fusion). 46,XY males have normal-appearing genitalia but may have hyperpigmented scrotum/enlarged phallus.
• State newborn screening targets 17-hydroxyprogesterone (17-OHP), but premature infants often have false positives due to immaturity and stress.

Rigorous Diagnostic Workup

• Stat labs: Serum electrolytes, blood glucose, blood gas.
• Endocrine panel: Stat serum 17-OHP, cortisol, rennin activity, androstenedione, and ACTH levels.
• Karyotype (Chromosomal Microarray): Mandatory for any infant with ambiguous genitalia.
• Pelvic/Abdominal Ultrasound: Identify presence of uterus/ovaries or cryptorchidism.

Acute Adrenal Crisis Management

• Immediate fluid resuscitation: Isotonic normal saline bolus 20 mL/kg over 1 hour. Repeat as needed for shock.
• Dextrose: Give D10W bolus 2 mL/kg if hypoglycemic, then maintain with D5 or D10 normal saline continuous infusion.
• Glucocorticoid replacement: Hydrocortisone 25-50 mg/m2/day IV divided every 6-8 hours (or 1-2 mg/kg IV stat push in crisis).
• Mineralocorticoid replacement: Fludrocortisone 0.05-0.1 mg PO daily (once PO feeds tolerated).
• Sodium supplementation: 1-2 mEq/kg/day of NaCl added to feeds.

Diagnostic & Management Algorithm

• CAH Crisis Algorithm: [START] Shock + Hyponatremia + Hyperkalemia -> [ACTION] NS Bolus + Draw 17-OHP -> [PHARMACOLOGY] Hydrocortisone 50-100 mg/m2 IV Stat -> [MONITOR] Glucose and ECG

References

1. Speiser PW, Arlt W, Auchus RJ, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab.