What is the recommended initial management for a newborn with classic salt‑wasting 21‑hydroxylase deficiency (congenital adrenal hyperplasia)?

Management of Classic Salt-Wasting 21-Hydroxylase Deficiency in Newborns

Immediate treatment of a newborn with classic salt-wasting congenital adrenal hyperplasia requires three components: intravenous hydrocortisone 100 mg followed by stress-dose glucocorticoid replacement, fludrocortisone 100-200 µg daily, and aggressive fluid resuscitation with isotonic saline if the infant presents in adrenal crisis. 1, 2

Acute Stabilization (First 24-48 Hours)

If Presenting in Adrenal Crisis

• Administer IV hydrocortisone 100 mg bolus immediately—do not delay for diagnostic testing 3, 1
• Infuse 0.9% normal saline at 1 L/hour (or age-appropriate rate) until hemodynamic stability is achieved 3, 1
• Continue hydrocortisone 100 mg IV every 6-8 hours until the infant is stable and able to take oral medications 1
• Draw blood for cortisol and ACTH before giving steroids if possible, but never delay treatment 3

If Diagnosed Before Crisis (e.g., Newborn Screening or Ambiguous Genitalia)

• Start oral hydrocortisone immediately at stress doses (approximately 25-100 mg/m² per day in divided doses) 4, 5
• Begin fludrocortisone 100-200 µg daily as a single morning dose 2, 6, 5
• Add oral sodium chloride supplementation (1-2 g daily in divided doses) 7, 5

Maintenance Therapy (After Stabilization)

Glucocorticoid Replacement

• Hydrocortisone is the only appropriate glucocorticoid for infants and children with CAH—never use dexamethasone or long-acting steroids 8, 1, 4
• Target maintenance dose: 10-15 mg/m² per day (approximately 6-10 mg/m² per day), divided into 3 doses 1, 4
• Typical dosing schedule: give the first dose immediately upon awakening, second dose at midday, and third dose 4-6 hours before bedtime 8, 1
• For a newborn, this translates to approximately 2.5 mg three times daily initially, adjusted based on body surface area 4, 5

Mineralocorticoid Replacement

• All infants with classic salt-wasting CAH require fludrocortisone—this is not optional 2, 5
• Starting dose: 100-200 µg daily as a single morning dose 2, 6, 5
• Infants typically require higher doses per body surface area than older children or adults 7, 6
• A practical dosing algorithm based on age: 6
  • 0-6 months: 200 µg daily
  • 7-18 months: 150 µg daily
  • 19-24 months: 125 µg daily

Sodium Supplementation

• Add oral sodium chloride 1-2 g daily in divided doses during infancy 7, 5
• Sodium needs are highest in the first 6 months and decrease as the infant matures 6
• Advise unrestricted salt intake in the diet as the child grows 8, 7

Monitoring Parameters

Biochemical Monitoring

• Check serum sodium, potassium, and glucose at diagnosis and during the first month, then monthly for the first 6 months 6, 5
• Measure plasma renin activity (PRA) to guide fludrocortisone dosing—target is upper normal range 7, 6
• Monitor 17-hydroxyprogesterone (17-OHP) and androstenedione every 3 months to assess glucocorticoid adequacy 4, 5
• The absence of hyperkalemia does not rule out inadequate mineralocorticoid replacement, as hyperkalemia occurs in only 50% of cases 3

Clinical Monitoring

• Assess blood pressure in supine and standing positions at each visit—orthostatic hypotension indicates under-replacement 7
• Monitor for salt craving, which suggests inadequate mineralocorticoid replacement 8, 7
• Track growth velocity and weight gain monthly—over-replacement causes excessive weight gain and growth suppression 1, 4
• Check for peripheral edema or hypertension, which indicate fludrocortisone over-replacement 7

Critical Pitfalls to Avoid

Dosing Errors

• Never use prednisolone, prednisone, or dexamethasone as maintenance therapy in infants—only hydrocortisone is appropriate 8, 1, 4
• Do not under-dose fludrocortisone out of fear of hypertension—under-replacement predisposes to recurrent adrenal crises 7
• Never stop fludrocortisone completely even if mild hypertension develops—reduce the dose instead 7

Monitoring Failures

• Do not rely on electrolytes alone to assess adequacy—hyponatremia may be mild and hyperkalemia is absent in 50% of cases 3
• Never fast an infant with CAH for more than 4-6 hours—check blood glucose hourly if fasting exceeds 4 hours 8
• Do not delay treatment of suspected adrenal crisis to obtain diagnostic tests—mortality is high if untreated 3, 1

Drug Interactions

• Avoid medications that interfere with fludrocortisone: diuretics, acetazolamide, NSAIDs, and liquorice 8, 7
• Avoid grapefruit juice and liquorice, which potentiate mineralocorticoid effects 8, 7

Stress Dosing and Emergency Preparedness

Sick Day Rules

• Triple the hydrocortisone dose during fever >38.5°C, vomiting, diarrhea, or significant illness 1, 4
• If the infant cannot tolerate oral medications due to vomiting, administer hydrocortisone 100 mg IM immediately and seek emergency care 1
• Continue fludrocortisone at the usual dose during illness—only glucocorticoid needs increase 7

Family Education

• Train parents to administer IM hydrocortisone 100 mg and provide an emergency injection kit 1
• Ensure the infant wears a medical alert bracelet indicating adrenal insufficiency 1, 7
• Provide a steroid emergency card with dosing instructions for healthcare providers 8, 1

Surgical Stress Dosing

For Feminizing Genitoplasty or Other Major Surgery

• Administer hydrocortisone 2 mg/kg IV at induction of anesthesia 8
• Continue hydrocortisone 2 mg/kg IV every 4 hours postoperatively, or use a continuous infusion of 50 mg/m²/day 8
• Resume oral hydrocortisone at double the maintenance dose once enteral intake is established, then taper to normal dosing over 48 hours 8
• Resume fludrocortisone at the usual dose once oral intake is established 7