Lilly Deutschland GmbH, Werner-Reimers-Strasse 2-4, 61352 Bad Homburg, Germany.
Eur J Endocrinol. 2013 Nov 22;170(1):13-21. doi: 10.1530/EJE-13-0643. Print 2014 Jan.
We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD).
Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were GH-naïve at baseline and GH-treated in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study.
Development of MPHD was assessed from investigator diagnoses, adverse events, and concomitant medications. Analyses were performed for all patients and for those who developed MPHD within 4.5 years or had ≥3.5 years, follow-up and continued to have IGHD (4-year cohort).
MPHD developed in 118/5805 (2.0%) children overall, and in 96/1757 (5.5%) in the 4-year cohort. Patients who developed MPHD had more profound GHD, with decreased height SDS, IGF1 SDS and peak stimulated GH, and greater height decrement vs target, compared with children who continued to have IGHD (P<0.001 for each variable). Delivery complications, congenital anomalies, and perinatal/neonatal adverse events occurred more frequently in patients who developed MPHD. The most frequent additional deficiency was TSH (82 patients overall); four patients developed two pituitary hormone deficiencies and one developed three deficiencies. Multivariable logistic regression indicated that years of follow-up (odds ratio 1.55), baseline age (1.17), baseline height SDS (0.69), and peak stimulated GH (0.64) were associated with the development of MPHD.
MPHD is more likely to develop in patients with more severe idiopathic IGHD. Older baseline age, lower baseline height SDS, and longer follow-up duration are associated with increased risk of development of MPHD.
我们评估了最初被诊断为特发性孤立性生长激素缺乏症（IGHD）的儿童在后来发展为多种（多种）垂体激素缺乏症（MPHD）的特征。
对 5805 名特发性 IGHD 儿科患者的数据进行了分析，这些患者在基线时为 GH 初治且在多国、观察性遗传和神经内分泌学矮小国际研究中接受 GH 治疗。
通过研究者诊断、不良事件和伴随药物来评估 MPHD 的发展。对所有患者以及在 4.5 年内发生 MPHD 或随访时间≥3.5 年且继续患有 IGHD 的患者（4 年队列）进行了分析。
总体而言，118/5805（2.0%）名儿童发生了 MPHD，4 年队列中 96/1757（5.5%）名儿童发生了 MPHD。与继续患有 IGHD 的儿童相比，发生 MPHD 的患者 GH 缺乏更严重，身高 SDS、IGF1 SDS 和峰值刺激 GH 降低，身高增长较目标值下降更大（各变量 P<0.001）。与继续患有 IGHD 的儿童相比，发生 MPHD 的患者更常出现分娩并发症、先天性异常和围产期/新生儿不良事件。最常见的其他缺乏症是 TSH（总体 82 例）；有 4 名患者发生了两种垂体激素缺乏症，1 名患者发生了三种缺乏症。多变量逻辑回归表明，随访年限（比值比 1.55）、基线年龄（1.17）、基线身高 SDS（0.69）和峰值刺激 GH（0.64）与 MPHD 的发生有关。
在更严重的特发性 IGHD 患者中，更有可能发生 MPHD。较大的基线年龄、较低的基线身高 SDS 和较长的随访时间与 MPHD 发生的风险增加相关。
