Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height

Abstract

Abstract Objective: To review the characteristics of children with non-classical 21-hydroxylase deficiency (NC-21-OHD) diagnosed during infancy and childhood, and to evaluate the relationship of pubertal and bone age maturation at initiation of glucocorticoid therapy with the course of puberty and final height. Design: We retrospectively compared the course of puberty, growth pattern and final height in two groups of patients: group A (two males, six females), hydrocortisone (HC) treatment 7·5–15 mg/m2 per 24 h, initiated ≥1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present. Participants: Thirteen girls and two boys with NC-21-OHD diagnosed at age range 0·5–10·6 years were followed-up for 9·0 ± 3·8 years (mean±s.d.). Therapy with HC was initiated because of signs of hyperandrogenism, accelerated growth and bone maturation, or true precocious puberty. The HC dose was adjusted according to linear growth and basal plasma androgen levels. Results: Puberty and peak height velocity developed significantly earlier in the girls of group B: gonadarche at 7·9 ± 1·4 years and peak height velocity at 9·2 ± 1·4 years vs 10·2 ± 0·4 years (P = 0·002) and 11·5 ± 0·7 years (P = 0·006) in group A. Menarche, however, occurred only slightly earlier in group B (12·0 ± 1·1 vs 12·8 ±0·5 years, P = 0·068). All eight children in group A achieved a final height within the range of their mean parental height standard deviation scores (SDS) in comparison with only 1/7 in group B (P = 0·0014). Seven of eight patients who started therapy before a bone age of 9 years achieved a final height within the parental height SDS range, compared with 2/7 who started therapy later (P = 0·041). The final height SDS was significantly better for group A (0·05 ± 0·19, mean ± s.e.m.) than group B (−1·63 ± 0·23, P = 0·0007), even when adjusted for a significant effect of the mean parental height SDS (A, −0·63 ± 0·28; B, −0·89 ± 0·31, P = 0·0245, ANCOVA). Conclusion: Every child with signs of excess androgen activity or early puberty should be studied for the possibility of NC-21-OHD. Screening programs for populations with a high frequency of the gene for NC-21-OHD would facilitate early diagnosis and treatment. Pubertal stage and bone age at the introduction of therapy dictate height prognosis. Initiation of therapy before puberty with careful follow-up and HC dose adjustment can assure the achievement of genetic adult height. European Journal of Endocrinology 136 188–195