Lawrence Neil R, Bacila Irina, Tonge Joseph, Dawson Jeremy, Collins Gary S, Lang Zi-Qiang, Bryce Jillian, Alimussina Malika, Chen Minglu, Ali Salma Rashid, Adam Safwaan, van den Akker Erica L T, Bachega Tânia Aparecida Sartori Sanchez, Baronio Federico, Birkebæk Niels Holtum, Bonfig Walter, Claahsen-van der Grinten Hedi, Cools Martine, Costa Eduardo Correa, Debono Miguel, de Vries Liat, Flück Christa E, Gazdagh Gabriella, Güven Ayla, Hannema Sabine E, Iotova Violeta, van der Kamp Hetty J, Krone Ruth, Leka-Emiri Sofia, Clemente-León María, Lichiardopol Corina Raducanu, Markosyan Renata L, Milenkovic Tatjana, de Miranda Mirela Costa, Neumann Uta, Newell-Price John, Poyrazoğlu Şükran, Probst-Scheidegger Ursina, Russo Gianni, De Sanctis Luisa, Seneviratne Sumudu Nimali, Stancampiano Marianna Rita, Tadokoro-Cuccaro Rieko, Thankamony Ajay, Vieites Ana, Wasniewska Malgorzata, Yeste Diego, Tomlinson Jeremy, Ahmed S Faisal, Krone Nils
Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Management School, University of Sheffield, Sheffield S10 2TN, United Kingdom.
Eur J Endocrinol. 2025 Apr 30;192(5):529-539. doi: 10.1093/ejendo/lvaf060.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) affects approximately 1 in 15 000 individuals. We leveraged the power of multicentre registry data to assess the trend and predictors of blood pressure (BP) within children and young persons with 21OHD to inform monitoring strategies.
Data from the International CAH Registry in patients younger than 20 years was compared to normative values. Values of BP were modeled to create reference curves, multiple change point analysis applied to quantify the difference with normative data. Covariate adjustment was informed by a directed acyclic graph, prior to joint outcome regression modeling to accurately assess predictors of BP.
A total of 6436 visits within 554 patients (52.5% females) showed BP-Standard deviation scores (SDS) were higher at younger ages. Patients under five years had systolic BP-SDS of 1.6 (Q1:0.6-Q3:2.7) decreasing to 1.0 (Q1:0.2-Q3:1.8) over 5 years, equating to 31.0% over the 95th centile decreasing to 15.0%. Higher doses of fludrocortisone were associated with a small increase in systolic BP equivalent to 1.2 mmHg with every 100 µg extra fludrocortisone. Renin of 100µU/mL was associated with 4.6 mmHg lower systolic BP than a renin of 1µU/mL, higher 17OH-progesterone and androstenedione also predicted lower systolic and diastolic BP (P < .05).
Higher BP in children with 21OHD is common and particularly pronounced at a younger age, but may not be attributable to excessive mineralocorticoid replacement. There is a need to improve our understanding of the determinants of this raised BP as well as its long-term effects.
由于21-羟化酶缺乏（21OHD）导致的先天性肾上腺皮质增生症（CAH）影响约1/15000的个体。我们利用多中心登记数据的力量来评估21OHD儿童和青少年的血压（BP）趋势及预测因素，以为监测策略提供依据。
将国际CAH登记处中20岁以下患者的数据与正常参考值进行比较。对血压值进行建模以创建参考曲线，应用多重变化点分析来量化与正常数据的差异。在进行联合结局回归建模以准确评估血压预测因素之前，通过有向无环图进行协变量调整。
554例患者（52.5%为女性）共进行了6436次就诊，结果显示血压标准差评分（SDS）在较年轻年龄段更高。5岁以下患者的收缩压SDS为1.6（第一四分位数：0.6 - 第三四分位数：2.7），5年内降至1.0（第一四分位数：0.2 - 第三四分位数：1.8），相当于从第95百分位数以上的31.0%降至15.0%。更高剂量的氟氢可的松与收缩压小幅升高相关，每额外增加100μg氟氢可的松，收缩压升高相当于1.2mmHg。肾素水平为100µU/mL时的收缩压比肾素水平为1µU/mL时低4.6mmHg，较高的17-羟孕酮和雄烯二酮水平也预示着较低的收缩压和舒张压（P < 0.05）。
21OHD儿童的血压较高很常见，且在较年轻年龄段尤为明显，但可能并非归因于盐皮质激素替代过量。有必要更好地了解这种血压升高的决定因素及其长期影响。
