Salt-Wasting Crisis

Definition & Background

A salt-wasting crisis is an acute, life-threatening adrenal emergency characterized by severe mineralocorticoid (aldosterone) and glucocorticoid deficiency. It is most commonly a presentation of classic congenital adrenal hyperplasia (CAH) - specifically the salt-wasting variant due to 21-hydroxylase deficiency (CYP21A2 mutations) - though it can also occur in any form of primary adrenal insufficiency.

21-Hydroxylase deficiency accounts for 90-95% of CAH cases. Major loss-of-function mutations cause combined glucocorticoid AND mineralocorticoid deficiency (classic CAH).
75% of infants with classic CAH manifest the salt-losing, virilizing variant.
In countries without neonatal CAH screening, boys (who lack virilization signs at birth) typically present with life-threatening salt-wasting crisis in the first few weeks of life.

(Harrison's Principles of Internal Medicine 22E; Guyton and Hall Textbook of Medical Physiology)

Pathophysiology

The core mechanism involves deficiency of 21β-hydroxylase, which impairs synthesis of both cortisol and aldosterone:

Cortisol deficiency - removes negative feedback on the hypothalamic-pituitary axis → ACTH rises dramatically → adrenal hyperplasia → cortisol precursors (17-hydroxyprogesterone) and androgens accumulate
Aldosterone deficiency - loss of sodium retention in the collecting duct → urinary salt wasting → volume depletion → circulatory collapse
Precursor steroids are shunted into the androgen pathway, causing virilization of females (clitoromegaly, labial fusion)

The result: hyponatremia + hyperkalemia + metabolic acidosis + hypotension + hypoglycemia = adrenal crisis

(Tintinalli's Emergency Medicine; Guyton and Hall)

Clinical Features

Timing: Salt-wasting crisis typically presents in the second week of life (range: days 7-14 after birth).

Symptoms (vague and easily missed):

Lethargy, irritability
Poor feeding, vomiting
Poor weight gain
Progressive dehydration → shock

Signs on examination:

Hypotension, tachycardia
Signs of dehydration
Hyperpigmentation (scrotal/labial folds, nipples) - from elevated ACTH
Females: clitoromegaly, labial fusion
Males: genitalia may appear normal (diagnostic trap)
Possible altered mental status

Differential diagnosis includes: sepsis, congenital heart disease, other inborn errors of metabolism

(Tintinalli's Emergency Medicine, pp. 1012)

Laboratory Findings

Parameter	Finding
Sodium (Na+)	LOW (hyponatremia)
Potassium (K+)	HIGH - typically 6 to 12 mEq/L
Blood glucose	LOW (hypoglycemia possible due to poor feeding/vomiting)
Acid-base	Metabolic acidosis
17-Hydroxyprogesterone	Markedly elevated (diagnostic marker)
ACTH	Elevated

Key investigations:

Bedside glucose - urgent
Serum electrolytes (Na, K)
12-lead ECG - hyperkalemic changes (peaked T waves, widened QRS) may alter management
Steroid profile (17-OHP, ACTH) - obtain before treatment if possible, but do not delay treatment
Newborn screening result (if available)

Treatment (Emergency Management)

1. Vascular Access

Establish IV or IO access immediately.

2. Fluid Resuscitation

Normal saline 10-20 mL/kg IV bolus - fluid loss in CAH is isotonic, so NS is the appropriate replacement fluid
Repeat as needed for circulatory collapse

3. Treat Hypoglycemia

Dextrose 10%, 5 mL/kg IV if hypoglycemic

4. Steroid Replacement (urgent - do not delay)

Hydrocortisone (has both glucocorticoid AND some mineralocorticoid effect at high doses):
- Neonates: 25 mg IV/IO
- Toddlers/school-age: 50 mg IV/IO
- Adolescents: 100 mg IV/IO

High-dose hydrocortisone partially compensates for mineralocorticoid deficiency while providing urgent glucocorticoid replacement.

5. Manage Hyperkalemia

If ECG changes present, manage hyperkalemia aggressively (calcium gluconate, insulin/dextrose, etc.)
Monitor cardiac rhythm continuously

6. Avoid Hypotonic Fluids

Do NOT use hypotonic saline or free water - this worsens hyponatremia

Disposition

All infants with salt-wasting crisis require hospital admission
ICU admission for infants with: shock, severe hyperkalemia with ECG changes
Definitive long-term management: glucocorticoid + mineralocorticoid replacement (hydrocortisone + fludrocortisone) with sodium supplementation in infancy

(Tintinalli's Emergency Medicine, p. 1013)

Quick Summary Table

Feature	Detail
Most common cause	21-Hydroxylase deficiency (classic CAH)
Typical age of onset	Week 2 of life
Core deficiency	Aldosterone + cortisol
Classic electrolytes	Hyponatremia + hyperkalemia
Emergency drug	Hydrocortisone IV
Emergency fluid	Normal saline
Pitfall	Boys have normal genitalia - diagnosis often delayed

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