Two brothers with non-classical 21-hydroxylase deficiency: to treat or not to treat?
Variations in phenotype in 21-hydroxylase deficiency (21OHD) have cautioned against initiating treatment in the absence of abnormal clinical features. We report 2 Caucasian brothers with compound heterozygous mutations of the CYP21 gene and mild clinical and biochemical features of late-presenting 21OHD. The index case presented aged 8.5 years with mild genital virilization and bone age advanced by 5 years. Elevated basal and synacthen-stimulated 17-hydroxyprogesterone (17OHP; 22.4 and 246 nmol/l) and androstenedione (10.9 and 19.9 nmol/l) levels confirmed 21OHD. His younger brother was investigated at age 7.3 years, and although examination showed normal pre-pubertal genitalia, basal and synacthen-stimulated 17OHP (32.4 and 281 nmol/l) and androstenedione (6.2 and 9.0 nmol/l) were abnormal, and bone age was advanced by 1.5 years. Because of actual or incipient virilization, both patients were treated with glucocorticoid replacement 8-12 mg/m(2)/day. This decision is discussed in the context of published guidelines for the management of 21OHD.
Oberender
F
F
Department of Paediatric Endocrinology and Clinical Biochemistry, St. Bartholomew's and the Royal London School of Medicine and Dentistry, London, UK.
Rumsby
G
G
Perry
L A
LA
Savage
M O
MO
D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D001846:Bone Development; D002648:Child; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use; D008297:Male; D009154:Mutation; D010641:Phenotype; D012741:Sexual Maturation; D013255:Steroid 21-Hydroxylase / Q000235:genetics* / Q000378:metabolism*
D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone