Salt-Depletion Syndrome

Adrenal crisis or salt-losing signs most often associated with genital anomalies. Adaptation of steroid therapy, fluid management, and blood pressure monitoring are imperative.

Salt-Losing Syndrome; Fibiger-Debré Von Gierke Syndrome; De Crecchio Syndrome; Fibiger-Debré Syndrome; Gallais Syndrome; Pirie Syndrome; Adrenal Virilizing Syndrome; Female Pseudohermaphroditism; Macrogenitosomia Praecox; Pseudosexual Precocity; Suprarenal Genital Syndrome; Suprarenal Pseudohermaphroditism-Virilism-Hirsutism Syndrome; Virilizing Adrenocortical Hyperplasia.

Congenital Adrenal Hyperplasia has an incidence about 1:5000 live births; Salt-Losing Syndrome incidence has been evaluated at 1:26,292 live births.

Autosomal recessive.

The gene is located on 6p21.3. The disease is closely linked to HLA and results from deficiency in one or another of the enzymes involved in the cortisol biosynthesis. In approximately 95% of cases, 21-hydroxylation is impaired in the zona fasciculata of the adrenal cortex which prevent the conversion to 11-deoxycortisol, resulting in overproduction of adrenocorticotropic hormone (ACTH) and cortisol precursors. Three principal biochemically distinct types have been described: virilizing adrenal hyperplasia, mixed adrenal hyperplasia, and nonvirilizing adrenal hyperplasia. A fourth one, often defined as acquired, is sometime considered. Of these children, 75% have salt-losing syndrome.

Evocated shortly after birth in cases of salt-losing signs (vomiting, dehydration, electrolyte changes, cardiac arrhythmias, and even adrenal crisis) or virilization signs. Biological signs include elevated urinary 17-ketosteroids, normal or decreased urinary 17-hydroxycorticosteroids, elevated 17-OH progesterone in blood, elevated serum dehydroepiandrosterone (DHEA) sulfate, and abnormal blood and urinary sodium levels.

Salt-losing signs can be associated with hypertension, recurrent fever, and hypoglycemia. Adrenal crisis can occur spontaneously in patients affected with severe adrenal hyperplasia. It includes various signs (headache, weakness, vomiting, low blood pressure, dehydration, fever, coma, tachycardia, joint and abdominal pain, weight loss, tachypnea) and can lead to death. Clinical features can also include genital signs (hypospadias, masculinizing female sexual characteristics, testicular tumors in adults, virilization, gynecomastia in adults). Growth is accelerated but adult stature is often short.

Evaluate salt-loss severity (clinical, history, weight, blood and urinary electrolytes, urea, creatinine) and cardiac implications (clinical, iterative cardiac blood measurement, ECG, echocardiography). Laboratory investigations should include glycemia, cortisol, and blood gas analysis.

Electrolyte balance should be obtained before surgery. Blood pressure should be closely supervised during the perioperative period. An indwelling arterial catheter is recommended for major procedures or in case of emergency. Strict asepsis is necessary in patients with steroid therapy. Glycemia and electrolytes should be regularly measured during the perioperative period.

Steroid therapy must be adapted to the importance of the surgical stress and consist in the administration of hydrocortisone 2 mg/kg. Prophylactic antibiotics are indicated in immunodeficient patients. Hypnomidate is contraindicated because of its effect on the adrenal gland. Succinylcholine should be avoided in patients presenting electrolytes instability (risk of hyperkalemia). Adrenal crisis can require vasoactive drugs (to support low blood pressure), supplementary hydrocortisone, and appropriate fluid regiment with extra sodium.

Wilkins Disease: Individuals affected with this medical condition present with pseudospasm of the pylorus, vomiting, severe dehydration, and death.

3β-Hydroxysteroid Dehydrogenase Deficiency: Characterized by the evidence of less virilization but more severe salt wasting.

17Alpha-Hydroxylase Deficiency: Characterized by similar symptomalogy previously described and in addition, the association with significant hypertension and hypochloremic, hypokalemic alkalosis.