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Hypoaldosteronism in three sibs due to 18-dehydrogenase deficiency
Insights
Congenital adrenal hyperplasia patients with isolated aldosterone deficiency require only mineralocorticoid treatment. Fludrocortisone is the preferred oral therapy for this salt-losing syndrome.
Area of Science:
- Endocrinology
- Genetics
- Pediatrics
Background:
- Congenital adrenal hyperplasia (CAH) is a group of genetic disorders affecting adrenal hormone synthesis.
- The salt-losing form of CAH presents with severe electrolyte imbalances in neonates.
Observation:
- Three siblings presented with a neonatal salt-losing syndrome, diagnosed as CAH.
- Treatment with glucocorticoids, mineralocorticoids, and salt was initiated.
- With age, steroid replacement needs decreased, prompting re-evaluation.
Findings:
- Re-investigation revealed normal cortisol synthesis but a block in aldosterone synthesis due to 18-dehydrogenase deficiency.
- This specific defect isolates aldosterone production failure.
Implications:
- Treatment for isolated aldosterone deficiency should focus solely on mineralocorticoid replacement.
- Oral fludrocortisone is recommended for long-term management over intramuscular deoxycorticosterone.
- Low-dose fludrocortisone is unlikely to suppress the hypothalamic-pituitary-adrenal axis.
Abstract:
Three sibs all presented in the early neonatal period with a salt-losing syndrome. The salt-losing form of congenital adrenal hyperplasia was diagnosed and appropriate treatment with glucocorticosteroids, mineralocorticosteroids, and additional dietary salt started. Although early life was maintained with difficulty, with age all 3 children required decreasing amounts of replacement steroids to maintain normal plasma electrolyte balance. They were reinvestigated at the ages of 15 years and 8 years (twins), when cortisol synthesis and metabolism proved normal, but aldosterone synthesis was blocked by deficiency of 18-dehydrogenase. Rational treatment of these cases of a salt-losing syndrome in which aldosterone synthesis alone is blocked due to lack of the enzyme 18-dehydrogenase requires the administration of a mineralocorticosteroid drug only. Since deoxycorticosterone (acetate or pivalate) requires intramuscular administration, as life-long therapy oral fludrocortisone is preferable. Although fludrocortisone has glucocorticoid activity, the "hydrocortisone equivalent" effect of the small dosage used was unlikely to inhibit either pituitary corticotrophin or growth hormone production.