Weintrob N, Dickerman Z, Sprecher E, Galatzer A, Pertzelan A
Institute of Pediatric and Adolescent Endocrinology, Schneider Children's Medical Center, Petah Tiqva, Israel.
Eur J Endocrinol. 1997 Feb;136(2):188-95. doi: 10.1530/eje.0.1360188.
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.
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 > or = 1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present.
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.
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).
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.
回顾婴儿期和儿童期诊断为非经典型21-羟化酶缺乏症（NC-21-OHD）患儿的特征，并评估糖皮质激素治疗开始时青春期和骨龄成熟与青春期进程及最终身高的关系。
我们回顾性比较了两组患者的青春期进程、生长模式及最终身高：A组（2名男性，6名女性），每24小时氢化可的松（HC）治疗剂量为7.5 - 15 mg/m²，在真性青春期开始前≥1年开始治疗；B组（7名女性），在出现真性青春期的首个体征时开始治疗。
13名女孩和2名男孩，诊断为NC-21-OHD时年龄在0.5 - 10.6岁，随访9.0±3.8年（均值±标准差）。因雄激素过多、生长加速和骨成熟或真性性早熟体征而开始HC治疗。HC剂量根据线性生长和基础血浆雄激素水平进行调整。
B组女孩青春期和身高增长峰值速度显著提前：性发育初潮年龄为7.9±1.4岁，身高增长峰值速度出现年龄为9.2±1.4岁，而A组分别为10.2±0.4岁（P = 0.002）和11.5±0.7岁（P = 0.006）。然而，B组月经初潮仅略早于A组（12.0±1.1岁 vs 12.8±0.5岁，P = 0.068）。A组所有8名儿童的最终身高在其父母平均身高标准差评分（SDS）范围内，而B组仅1/7达到该范围（P = 0.0014）。8名骨龄9岁前开始治疗的患者中有7名最终身高在父母身高SDS范围内，而骨龄9岁后开始治疗的患者中只有2/7达到该范围（P = 0.041）。即使校正了父母平均身高SDS的显著影响后，A组的最终身高SDS仍显著优于B组（0.05±0.19，均值±标准误）（A组为 - 0.63±0.28；B组为 - 0.89±0.31，P = 0.0245，协方差分析）。
每一个有雄激素活性过高或青春期过早迹象的儿童都应进行NC-21-OHD可能性的检查。对NC-21-OHD基因高频率人群开展筛查项目将有助于早期诊断和治疗。治疗开始时的青春期阶段和骨龄决定身高预后。青春期前开始治疗并仔细随访及调整HC剂量可确保达到遗传成人身高。
