Department of Pediatrics, Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Pediatrics, Division of Endocrinology and Diabetes, Stanford University School of Medicine, Palo Alto, CA, USA.
J Pediatr Endocrinol Metab. 2022 Dec 5;36(2):185-194. doi: 10.1515/jpem-2022-0468. Print 2023 Feb 23.
Prader-Willi syndrome (PWS) is characterized by obesity, growth hormone deficiency, hypogonadism, and a high prevalence of premature adrenarche despite reported hypothalamic-pituitary-adrenal axis dysfunction. While idiopathic premature adrenarche is associated with accelerated pre-pubertal growth and advanced bone age, the consequences of elevated adrenal androgens on growth and bone maturation in PWS remain unknown. This study therefore sought to describe age-related changes in dehydroepiandrosterone sulfate (DHEAS) and their effects on growth and bone maturation in PWS.
This retrospective observational study included 62 children with PWS. Simple and multiple regression models were constructed to relate age and BMI-SDS with DHEAS levels. Height velocity was compared to age and sex-based norms with t-tests and two-way ANOVA. Patterns in bone age Z-score were examined with two-way ANOVA, and the contributions of age, BMI-SDS, and DHEAS to bone age Z-score were analyzed with multiple regression.
DHEAS levels rose earlier and were less strongly correlated with age in males and females with PWS (R=0.12 and 0.30) compared to healthy controls (R=0.89 and 0.88) in a pattern unrelated to BMI-SDS (adjusted R=0.076, p=0.10 for age, and 0.29 for BMI-SDS). Mid-childhood height velocity was increased in males and preserved in females with PWS before declining at the age of expected puberty (p<0.0001). Peri-adrenarchal bone age was advanced in a manner associated with DHEAS but not BMI-SDS (p<0.0001; adjusted R=0.48, p=0.0014 for DHEAS, and 0.78 for BMI-SDS).
An obesity-independent increase in adrenal androgens is associated with accelerated mid-childhood growth and bone maturation in PWS.
普拉德-威利综合征（PWS）的特征是肥胖、生长激素缺乏、性腺功能减退和高促肾上腺皮质激素释放激素轴功能障碍，但肾上腺过早活跃的患病率仍然很高。虽然特发性肾上腺过早活跃与加速青春期前生长和提前骨龄有关，但升高的肾上腺雄激素对 PWS 生长和骨成熟的影响仍不清楚。因此，本研究旨在描述脱氢表雄酮硫酸盐（DHEAS）与年龄相关的变化及其对 PWS 生长和骨成熟的影响。
本回顾性观察研究纳入了 62 名 PWS 患儿。构建简单和多元回归模型，以研究年龄和 BMI-SDS 与 DHEAS 水平的关系。通过 t 检验和双向方差分析将身高速度与年龄和性别标准进行比较。通过双向方差分析检查骨龄 Z 评分的模式，并通过多元回归分析年龄、BMI-SDS 和 DHEAS 对骨龄 Z 评分的贡献。
与健康对照组（R=0.89 和 0.88）相比，PWS 男性和女性的 DHEAS 水平升高更早，与年龄的相关性更弱（R=0.12 和 0.30），且与 BMI-SDS 无关（调整后的 R=0.076，p=0.10 用于年龄，0.29 用于 BMI-SDS）。在青春期前，PWS 男性的中期身高速度增加，女性保持不变，然后在预期青春期时下降（p<0.0001）。性早熟的骨龄提前，与 DHEAS 相关，与 BMI-SDS 无关（p<0.0001；调整后的 R=0.48，p=0.0014 用于 DHEAS，0.78 用于 BMI-SDS）。
与肥胖无关的肾上腺雄激素增加与 PWS 中儿童中期生长和骨成熟加速有关。
