Merke Deborah P, Mallappa Ashwini, Parker Megan, Sukin Charles, Kulkarni Sarah E, Keil Margaret F, Van Ryzin Carol, Hill Suvimol Chirathivat, Reynolds James C, Cutler Gordon B, Sinaii Ninet
Department of Pediatrics, National Institutes of Health Clinical Center, Bethesda, MD 20892, USA.
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
J Clin Endocrinol Metab. 2025 Jun 17;110(7):e2171-e2182. doi: 10.1210/clinem/dgae824.
Height outcome in patients with classic congenital adrenal hyperplasia (CAH) is suboptimal due to glucocorticoid and androgen excess.
In an open, randomized, controlled trial, children with classic CAH were randomized to receive a combination regimen of antiandrogen, aromatase inhibitor, reduced hydrocortisone, and fludrocortisone prior to puberty or standard therapy (hydrocortisone, fludrocortisone). Females continued on antiandrogen during puberty. The primary endpoint was adult height.
Of 62 children randomized, 45 completed the study. Adult height SDS did not differ between the investigational and control groups (-0.34 [0.93] vs -0.60 [0.89], respectively), mean difference 0.26 [95% CI -0.29, 0.82], P = .35), irrespective of midparental height, but was greater than the predicted adult height pretreatment in both groups (P < .001). Growth rate and rate of bone maturation were reduced in the investigational group prior to puberty, despite lower hydrocortisone dose (7.6 [1.5] vs 15.0 [3.6] mg/m2/day, P < .001), and improvement in predicted adult height appeared greater at pubertal onset (P = .049) compared to standard therapy. Antiandrogen treatment during puberty in girls allowed for lower-dose glucocorticoid, and improved height outcome (adult minus midparental height: -0.7 [4.6] vs -5.6 [5.2] cm, mean difference 4.9 [95% CI 0.09, 9.7], P = .046). Those who received GnRHa had lower growth rate (P = .023) and longer years of unchanged bone age (P = .017), regardless of treatment.
Prepubertal antiandrogen, aromatase inhibitor combination with reduced hydrocortisone improves short-term predicted height for children with CAH but does not result in taller adult stature than those treated with standard therapy, and is not recommended. Females may benefit from antiandrogen treatment during puberty.
经典型先天性肾上腺皮质增生症（CAH）患者由于糖皮质激素和雄激素过多，身高结局不理想。
在一项开放、随机、对照试验中，将经典型CAH患儿在青春期前随机分为接受抗雄激素、芳香化酶抑制剂、氢化可的松减量及氟氢可的松的联合治疗方案或标准治疗（氢化可的松、氟氢可的松）。女性在青春期继续接受抗雄激素治疗。主要终点为成人身高。
在随机分组的62名儿童中，45名完成了研究。研究组和对照组的成人身高标准差评分无差异（分别为-0.34[0.93]和-0.60[0.89]），平均差异为0.26[95%可信区间-0.29，0.82]，P = 0.35），与父母平均身高无关，但两组的成人身高均高于治疗前预测的成人身高（P < 0.001）。尽管氢化可的松剂量较低（7.6[1.5]与15.0[3.6]mg/m²/天，P < 0.001），研究组在青春期前的生长速度和骨成熟速度仍降低，与标准治疗相比，青春期开始时预测成人身高的改善似乎更大（P = 0.049）。女孩在青春期接受抗雄激素治疗可使用较低剂量的糖皮质激素，并改善身高结局（成人身高减去父母平均身高：-0.7[4.6]与-5.6[5.2]cm，平均差异4.9[95%可信区间0.09，9.7]，P = 0.046）。无论治疗情况如何，接受促性腺激素释放激素类似物（GnRHa）治疗的患者生长速度较低（P = 0.023），骨龄不变的时间较长（P = 0.017）。
青春期前使用抗雄激素、芳香化酶抑制剂联合减量氢化可的松可改善CAH儿童的短期预测身高，但不会使成人身高高于接受标准治疗的患者，因此不推荐使用。女性在青春期可能从抗雄激素治疗中获益。
