Department of CLINTEC, Karolinska Institutet, Stockholm, Sweden.
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Horm Res Paediatr. 2024;97(5):445-455. doi: 10.1159/000535403. Epub 2023 Nov 28.
Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency results in inadequate cortisol and aldosterone synthesis and concomitant overproduction of adrenal androgens. Despite adequate replacement, impaired growth and overweight remain a clinical challenge. The main objective was to investigate the differences in growth, final height (FH), and body mass index (BMI) between different CYP21A2 genotype groups and glucocorticoid treatment strategies during the different phases of growth.
This is a population-based observational cohort study from diagnosis to FH. A total of 86 subjects were diagnosed with CAH in Sweden during 1989-1994. Eighty subjects were followed until FH. There were no interventions apart from the clinical standard of care treatment for CAH. The main outcome measure was the corrected FH standard deviation score (cFH SDS) and its correlation with genotype, accumulated total glucocorticoid dose, and treatment strategy. In addition, BMI and growth trajectories during infancy, childhood, and adolescence were studied.
FH was shorter in patients with the more severe CYP21A2 genotypes. Treatment doses of glucocorticoid were within the international treatment recommendations (10-15 mg/m2). Patients with the null and I2 splice genotypes lost approximately 1 SD in FH, whereas patients with the milder genotypes (I172N, P30L, and V281L) were within 0.5 to 0 SDS from target height. cFH SDS was negatively affected by the use of prednisolone but did not correlate with overall glucocorticoid treatment dose calculated as hydrocortisone equivalents. BMI at 18 years was higher in patients treated with prednisolone but did not correlate with genotype.
Corrected FH was more affected in patients with severe CYP21A2 genotypes. The addition of a low dose of prednisolone to the hydrocortisone treatment, despite an equivalent total dose of glucocorticoids, was associated with shorter FH and higher BMI in growing subjects with CAH.
由于 21α-羟化酶缺乏导致先天性肾上腺增生（CAH），导致皮质醇和醛固酮合成不足，同时肾上腺雄激素产生过多。尽管进行了充分的替代治疗，但生长受损和超重仍然是一个临床挑战。主要目的是研究不同 CYP21A2 基因型组之间的生长、最终身高（FH）和体重指数（BMI）差异，以及不同生长阶段糖皮质激素治疗策略的差异。
这是一项基于人群的观察性队列研究，从诊断到 FH。1989-1994 年期间，瑞典共有 86 名患者被诊断为 CAH。80 名患者接受了 FH 随访。除了 CAH 的临床标准治疗外，没有进行任何干预。主要观察指标是校正后的 FH 标准差评分（cFH SDS）及其与基因型、累积总糖皮质激素剂量和治疗策略的相关性。此外，还研究了婴儿期、儿童期和青春期的 BMI 和生长轨迹。
FH 在 CYP21A2 基因型更严重的患者中较短。糖皮质激素的治疗剂量在国际治疗建议范围内（10-15mg/m2）。无功能和 I2 剪接基因型的患者 FH 丢失约 1 SDS，而较轻基因型（I172N、P30L 和 V281L）的患者 FH 丢失在 0.5-0 SDS 之间。cFH SDS 受泼尼松龙的影响，但与以氢化可的松当量计算的总糖皮质激素治疗剂量无关。接受泼尼松龙治疗的患者 18 岁时的 BMI 较高，但与基因型无关。
严重 CYP21A2 基因型的患者 FH 受影响更大。在氢化可的松治疗中添加低剂量泼尼松龙，尽管糖皮质激素的总剂量相同，但与 CAH 生长中的患者 FH 缩短和 BMI 升高有关。
