Severe Salt-Losing 3β-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes of HSD3B2 c.35G>A Homozygotes.

Journal Article (Journal Article)

Context

3-β-hydroxysteroid dehydrogenase (HSD3B2) deficiency accounts for less than 5% of congenital adrenal hyperplasia worldwide, but is relatively common among the Old Order Amish of North America due to a HSD3B2 c.35G>A founder mutation.

Objective

We review clinical presentation, disease course, treatment, and outcomes of a genetically homogenous population of HSD3B2-deficient patients.

Design and participants

This was a retrospective case series: anthropometric, biochemical, and clinical data from 16 (six male) affected subjects (age, 7.2 ± 6.4 y) were compared to reference data from 12 age-matched unaffected siblings.

Setting

The setting was the Clinic for Special Children, a nonprofit rural community health center in Lancaster, Pennsylvania.

Main outcome measures

The main outcome measures were growth, skeletal maturation, sexual development, blood pressure, glucocorticoid dose, pituitary-adrenal homeostasis, and long-term morbidity.

Results

Exogenous glucocorticoid requirement was dichotomous: a standard-dose group (n = 9) required 15.4 ± 4.9 mg/m(2)/d hydrocortisone equivalent, whereas a high-dose group required much larger and more variable doses (hydrocortisone equivalent, 37.8 ± 15.4 mg/m(2)/d) (P < .0001). Despite glucocorticoid doses 2-fold higher than the standard-dose group, high-dose patients: 1) had ACTH, 17-hydroxypregnenolone, and dehydroepiandrosterone levels that were 10-fold, 20-fold, and 20-fold higher, respectively; 2) were exclusively affected by signs of sex steroid excess; and 3) tended to have more iatrogenic complications.

Conclusions

Patients with HSD3B2 deficiency and 21-hydroxylase deficiency suffer similar morbid complications from under- and overtreatment, but HSD3B2 deficiency is associated with a distinctive pattern of sex steroid dysmetabolism. Disease- and treatment-related morbidities are almost exclusively observed among subjects who have a high exogenous glucocorticoid requirement.

Full Text

Duke Authors

Cited Authors

  • Benkert, AR; Young, M; Robinson, D; Hendrickson, C; Lee, PA; Strauss, KA

Published Date

  • August 2015

Published In

Volume / Issue

  • 100 / 8

Start / End Page

  • E1105 - E1115

PubMed ID

  • 26079780

Electronic International Standard Serial Number (EISSN)

  • 1945-7197

International Standard Serial Number (ISSN)

  • 0021-972X

Digital Object Identifier (DOI)

  • 10.1210/jc.2015-2098

Language

  • eng