Case In Point: Infant With Aldosterone Deficiency

A 45-day-old boy was referred for evaluation of persistent hyponatremia and hyperkalemia. On the 9th day of the boy's life, his serum potassium level was elevated (8 mEq/L) and on the 12th day, his serum sodium level was low (131 mEq/L). Supplementation with sodium chloride was initiated.

The patient was born at 30 weeks gestation to a 39-year-old woman. Delivery was by cesarean section because of the fetus's breech presentation and because of premature membrane rupture, which had occurred 6 weeks earlier. The mother was given dexamethasone during labor and the baby received intratracheal surfactant during neonatal resuscitation.

At birth, the baby weighed 1470 g (50th percentile); his head circumference was 28.5 cm (50th percentile); and length was 41 cm (50th percentile). Apgar scores were 5 and 7 at 1 and 5 minutes, respectively. Respiratory distress subsequently developed, and the patient was intubated in the delivery room and transferred to the neonatal ICU. Hyaline membrane disease was diagnosed, and the patient was placed on ventilatory support until day 6 of life.

He received total parenteral nutrition (TPN) exclusively until day 6. He was then fed breast milk with human milk fortifier (HMF); this was supplemented with TPN on day 7. By day 10, the child was fed breast milk with HMF exclusively. Sodium supplementation was started at 1 mEq/ feed on day 12; this was gradually increased to 4 mEq/4h on day 40.

The patient had no history of seizure-like activity, irritability, drowsiness, excessive or decreased urination, altered feeding patterns, diuretic use, head trauma, or abdominal distention. There was no family history of similar illness or of ambiguous genitalia.

On examination, the patient was alert, responsive, and comfortable. Both his weight and length had dropped to 10th percentile, however. His temperature was 36.1°C (97°F); heart rate, 154 beats per minute; respiratory rate, 52 breaths per minute; oxygen saturation, 98% on room air; and blood pressure, 70/36 mm Hg. Results of a systemic examination were normal. The genitourinary examination showed normal male genitalia with bilateral descended testicles.

Laboratory evaluation at the referring hospital showed that in addition to low serum sodium and a high serum potassium level, the patient's serum 11-deoxycortisol level was 120 ng/mL. Results of a newborn metabolic screen were negative for congenital adrenal hyperplasia. Plasma renin activity (PRA) was 113.18 ng/mL/h (normal, 2.0 to 3.7 ng/mL/h). Serum aldosterone was 29.7 ng/dL; this was thought to be low given the low serum sodium levels and high PRA.17-OH progesterone was 136 ng/dL (normal, 53 to 186 ng/dL for this age). Renal sonograms were normal.

On the day of presentation at our hospital (day 45 of life), the patient's serum sodium was 135 mEq/L; serum potassium, 6.5 mEq/L; blood urea nitrogen, 10 mg/dL; creatinine, 0.4 mg/dL; urinary sodium, 87 mEq/L; and urinary potassium, 48.6 mEq/L. Serum aldosterone level was 34 ng/dL (normal, 1 to 31 ng/dL); serum cortisol, 6.2 µg/dL (normal, 4 to 29 µg/dL); PRA, 299.3 ng/mL/h (normal, 2 to 3.7 ng/mL/h); 11-deoxycortisol, 67 ng/dL (normal, less than 30 ng/dL); deoxycorticosterone, 31 ng/dL (normal, 7 to 57 ng/dL); 17-OH progesterone, 134 ng/dL (normal, 40 to 200 ng/dL); 18-OH corticosterone, 950 ng/dL (normal, 5 to 220 ng/dL); and corticosterone, 535 ng/dL (normal, 80 to 1500 ng/dL). Head and renal sonograms were normal.

Breast milk analysis showed sodium and potassium levels of less than 75 and 13.6 mEq/L, respectively. An adrenocorticotropic hormone (ACTH) stimulation test showed the pre-ACTH aldosterone level to be 34 ng/dL; the post-ACTH aldosterone level was 37 ng/dL (not a significant increase).

The diagnosis of aldosterone deficiency, or corticosterone methyl oxidase (CMO) type II deficiency,was made. This diagnosis was based onthe increased 18-OH corticosterone level, the inappropriatelylow aldosterone level relative to the degree of hyponatremia and high PRA, and the increased ratio of 18-OH corticoste- rone to aldosterone.

Sodium chloride supplementation was given at 2 mEq/L with every feeding along with a low-iron infant formula (Similac PM 60/40). The patient had a partial response; fludrocortisone, 0.1 mg/d, was therefore added to the regimen. He responded well to this combination and his sodium level remained stable at 138 to 140 mEq/L.

At follow-up visits, the baby showed good catch-up growth.

ALDOSTERONE DEFICIENCY

The first 3 steps of aldosterone biosynthesis from cholesterol to progesterone are identical to those of cortisol biosynthesis. However, aldosterone synthase (CYP11B2) is only expressed in the zona granulosa of adrenal glands.^1,2 The most common cause of aldosterone deficiency is congenital adrenal hyperplasia (CAH) from 21-hydroxylase (CYP21) deficiency. In CAH, cortisol deficiency is associated with increased levels of sex steroids that can present as ambiguous genitalia in female infants.^1-4

Aldosterone deficiency is an autosomal recessive disorder characterized by a defect in the terminal step of aldosterone. Affected persons appear to be homozygous for 2 different mutations--Arg 181 Trp and Val 1385 Ala. Family members who are homozygous for only 1 of these mutations remain unaffected. This effect is associated with biochemical evidence of chronic salt depletion.^3-6

Two forms of aldosterone synthase deficiency are described--CMO deficiency types I and II. Clinical features of patients with either syndrome are identical; the only differences are found in the intermediate steroid profiles (Table).^7,8

The clinical presentation of aldosterone synthase deficiency and the severity of presentation vary with age. Newborns (within the first several weeks of life) exhibit a salt-wasting syndrome, which can present as failure to gain weight followed by signs of dehydration.⁴ Affected adults are usually asymptom- atic but may experience problems during periods of stress or acute illness (such as gastroenteritis) or in very hot climates where they may not tolerate salt losses.^1,2,5,7

If aldosterone deficiency is not corrected, the result may be hypotension from hypovolemia, shock, and sometimes death associated with hyponatremia, hyperkalemia, and hyperreninemia. Patients usually present with serum levels of sodium of 120 to 130 mEq/L and potassium of 6.0 to 8.5 mEq/L. Their PRA is markedly elevated and aldosterone levels are inappropriately low.

Diagnostic laboratory findings are hyponatremia, hyperkalemia, hyperreninemia, with hypoaldosteronemia. Other very important laboratory findings are normal cortisol and sex steroid levels that are appropriate for the infant's age. Patients with aldosterone synthase deficiency who present after infancy usually have anorexia, mild dehydration, and abnormal growth. Electrolyte abnormalities may be present, but most of the children older than 4 years have normal serum electrolyte levels at the time of diagnosis.^3,7,8

TREATMENT

Treatment of affected infants includes oral sodium supplementation (sodium chloride 1 to 2 g/d) and fludrocortisone (0.1 to 0.3 mg/d). Establishing normal fluid and electrolyte balance will result in rapid catch-up growth. Mineralocorticoid therapy (fludrocortisone) and sodium supplementation should be continued and the child should be monitored regularly throughout childhood. Older patients can be treated with fludrocortisone alone.^1-5

References:

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