Severe Salt-Losing 3ß-Hydroxysteroid Dehydrogenase Deficiency: Treatment and Outcomes of HSD3B2 c.35G>A Homozygotes.
J Clin Endocrinol Metab
; 100(8): E1105-15, 2015 Aug.
Article
in En
| MEDLINE
| ID: mdl-26079780
ABSTRACT
CONTEXT 3-ß-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 ANDPARTICIPANTS:
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 OUTCOMEMEASURES:
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:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Progesterone Reductase
/
Adrenal Hyperplasia, Congenital
/
Polymorphism, Single Nucleotide
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
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Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2015
Document type:
Article