Mineralocorticoid replacement during infancy for salt wasting congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Abstract

OBJECTIVE:The protocols for glucocorticoid replacement in children with salt wasting 21-hydroxylase deficiency are well established; however, the current recommendation for mineralocorticoid replacement is general and suggests individualized dose adjustments. This study aims to retrospectively review the 9-∝-fludrocortisone dose regimen in salt wasting 21-hydroxylase deficient children who have been adequately treated during infancy.METHODS:Twenty-three salt wasting 21-hydroxylase deficient patients with good anthropometric and hormonal control were followed in our center since diagnosis. The assessments of cortisone acetate and 9-∝-fludrocortisone doses, anthropometric parameters, and biochemical and hormonal levels were rigorously evaluated in pre-determined intervals from diagnosis to two years of age.RESULTS:The 9-∝-fludrocortisone doses decreased over time during the first and second years of life; the median fludrocortisone doses were 200 μg at 0-6 months, 150 μg at 7-18 months and 125 μg at 19-24 months. The cortisone acetate dose per square meter was stable during follow-up (median = 16.8 mg/m2/day). The serum sodium, potassium and plasma rennin activity levels during treatment were normal, except in the first month of life, when periodic 9-∝-fludrocortisone dose adjustments were made.CONCLUSIONS:The mineralocorticoid needs of salt wasting 21-hydroxylase deficient patients are greater during early infancy and progressively decrease during the first two years of life, which confirms that a partial aldosterone resistance exists during this time. Our study proposes a safety regiment for mineralocorticoid replacement during this critical developmental period.

A Case of Salt-Wasting 21-Hydroxylase Deficiency With Resistance to Aldosterone due to Urinary Tract Infection

“…The diagnosis/treatment guidelines for 21-OHD by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology recommend administering 0.025-0.2 mg/day of FC [ 5 ]. Our literature search found a patient who required a maximum dose of 0.35 mg/day [ 14 ]. In the present case, 0.3 mg/day of FC did not improve hyperkalemia; hence, the dose needed to be increased up to 0.36 mg/day.…”

“…The reason was speculated as follows: the expression of aldosterone receptors in the distal nephron is limited in a newborn and neonatal nephrons are known to be resistant to the actions of aldosterone [ 15 ]. Therefore, the required dose of FC is higher, especially at 0 to six months, than the dose administered after that; moreover, the dose range is wide because it depends on the large individual differences in sensitivity to aldosterone [ 14 ]. In addition, this resistance to aldosterone may be exacerbated by the presence of PHA caused by UTI and/or urinary tract abnormalities [ 16 ].…”

‘Don’t leap to a conclusion of sepsis!’ Congenital adrenal hyperplasia in male neonates: case series and literature review

“…15 The goal of HRT includes normalising androgen levels and total body sodium depletion for proper growth and development, as well as avoiding volume overload. 16 Mineralocorticoid needs of salt-wasting 21-hydroxylase deficiency patients are greater during early infancy and progressively decrease during the first two years of life (median fludrocortisone doses are 200 mg at 0-6 months, 150 mg at 7-18 months and 125 mg at 19-24 months), 9 and should be based on clinical and laboratory indices such as blood pressure, sodium and potassium levels, and plasma renin activity. 17 Sodium should be supplemented with 3% saline during infancy.…”

“…Patients with salt-losing disease require replacement with fludrocortisone, usually 0.1–0.2 mg o.d., and often require sodium supplementation (sodium chloride 0.5–5.0 mmol/kg/day). 9,10 Mineralocorticoid doses vary during infancy owing to improvement in sensitivity which improves with age and particularly during the first year of life. 11 The high mineralocorticoid doses required during infancy are explained by immaturity of renal function, limited sodium content of breast milk, and higher sodium requirement for growth and development.…”

Hiperplasia adrenal congênita em mulheres adultas: manejo de antigos e novos desafios

“…Quanto aos MC, adultos com a FC necessitam de doses menores de fludrocortisona (50-100 mcg/dia) comparadas às doses usadas nos primeiros anos de vida e infância (100-200 mcg/dia) (6,7,19,28). Não se sabe ao certo o mecanismo envolvido na melhora da sensibilidade com a idade, mas parece estar relacionado com a redução da resistência renal à ação dos MC, que ocorre após os primeiros anos de vida (29).…”