Acute and Ongoing Management of Classic Salt‑Wasting 21‑Hydroxylase Deficiency in Newborns

1. Immediate Stabilization in Adrenal Crisis

Administer an intravenous bolus of hydrocortisone 100 mg without waiting for laboratory confirmation, followed by 100 mg IV every 6–8 hours until the infant is hemodynamically stable and can tolerate oral medication. [@2]
Begin rapid isotonic saline infusion (0.9 % NaCl) at approximately 1 L / hour (age‑adjusted rate) until circulatory stability is achieved. [@2]
If feasible, obtain baseline cortisol and ACTH levels before steroid administration, but do not postpone treatment for testing. [@2]

Provide oral sodium chloride supplementation of 1–2 g per day in divided doses to meet early sodium requirements. [@3]

Hydrocortisone is the sole glucocorticoid recommended for infants and children with classic salt‑wasting CAH; long‑acting steroids such as dexamethasone, prednisolone, or prednisone must be avoided. [@4]
Target a maintenance dose of 10–15 mg / m² per day (approximately 6–10 mg / m² per day) divided into three equal doses. [@1]
Schedule doses as follows: first dose upon awakening, second dose at midday, and third dose 4–6 hours before bedtime. [@4]

All infants with classic salt‑wasting CAH require fludrocortisone; under‑dosing predisposes to recurrent adrenal crises. [@3]
Infants typically need higher fludrocortisone doses per body surface area than older children; dosing is usually 100–200 µg daily as a single morning dose. [@3]
Oral sodium chloride 1–2 g daily should be continued throughout infancy, with unrestricted dietary salt intake encouraged as the child grows. [@4]

Measure plasma renin activity (PRA) regularly to guide fludrocortisone dosing, aiming for values in the upper normal range. [@3]
Recognize that the absence of hyperkalemia does not exclude inadequate mineralocorticoid therapy; hyperkalemia is present in only ~50 % of under‑replaced infants. [@2]
At each visit, assess supine and standing blood pressure; orthostatic hypotension signals glucocorticoid or mineralocorticoid under‑replacement. [@3]
Monitor for salt craving, which indicates insufficient mineralocorticoid effect. [@4]
Track growth velocity and weight gain monthly; excessive weight gain or growth suppression suggests glucocorticoid over‑replacement. [@1]
Observe for peripheral edema or hypertension as markers of fludrocortisone over‑replacement. [@3]

Do not use prednisolone, prednisone, or dexamethasone for maintenance therapy in infants; hydrocortisone remains the only appropriate agent. [@4]
Do not withhold or stop fludrocortisone even if mild hypertension develops; instead, reduce the dose. [@3]
Do not rely solely on electrolyte panels to assess mineralocorticoid adequacy, because hyponatremia may be subtle and hyperkalemia absent in half of cases. [@2]
Avoid fasting infants with CAH for longer than 4–6 hours; if fasting exceeds 4 hours, monitor blood glucose hourly. [@5]
Do not delay treatment of a suspected adrenal crisis to obtain diagnostic tests, as untreated crisis carries high mortality. [@2]

Medications that can diminish fludrocortisone effectiveness include diuretics, acetazolamide, NSAIDs, and licorice‑containing products. [@4]
Grapefruit juice and licorice can potentiate mineralocorticoid effects and should be avoided. [@4]

Triple the usual hydrocortisone dose during fever > 38.5 °C, vomiting, diarrhea, or any significant illness. [@1]
If oral intake is impossible due to vomiting, give an immediate intramuscular injection of hydrocortisone 100 mg and seek emergency medical care. [@1]
Maintain the regular fludrocortisone dose during illness; only glucocorticoid dosing is increased. [@3]

Train caregivers to administer a 100 mg intramuscular hydrocortisone injection and provide them with an emergency injection kit. [@1]
Ensure the infant wears a medical‑alert bracelet indicating adrenal insufficiency. [@1]
Supply a steroid emergency card containing clear dosing instructions for healthcare providers. [@4]

At induction of anesthesia for major surgery (e.g., feminizing genitoplasty), give hydrocortisone 2 mg / kg intravenously. [@5]
Continue hydrocortisone 2 mg / kg IV every 4 hours post‑operatively, or use a continuous infusion of approximately 50 mg / m² per day. [@5]
Once enteral feeding resumes, restart oral hydrocortisone at double the usual maintenance dose, then taper back to the standard dose over the next 48 hours. [@5]
Reinstate fludrocortisone at the usual daily dose once oral intake is re‑established. [@3]