Fava Daniela, Guglielmi Davide, Pepino Carlotta, Angelelli Alessia, Casalini Emilio, Varotto Carolina, Panciroli Marta, Tedesco Caterina, Camia Tiziana, Naim Alessandro, Allegri Anna Elsa Maria, Patti Giuseppa, Napoli Flavia, Gastaldi Roberto, Parodi Stefano, Salerno Mariacarolina, Maghnie Mohamad, Di Iorgi Natascia
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy.
Pediatric Endocrinology Unit, Department of Pediatrics, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy.
J Clin Endocrinol Metab. 2024 Dec 18;110(1):78-90. doi: 10.1210/clinem/dgae408.
The 2019 American Association of Clinical Endocrinologists guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase.
The aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement.
Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST, and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies) and 18 severe organic GHD (≥3 hormone deficiencies).
Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis identified 7.3 μg/L as the optimal GH peak cutoff to GST [95% confidence interval (CI) 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value (PPV) 88.0%, negative predictive value (NPV) 95.7%] able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3 hormone deficiencies showed a GH peak <5 μg/L at ITT and <5.8 μg/L at GST but 1. The optimal cutoff for IGF-1 was -1.4 SD score (95% CI -1.94 to 0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population.
A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pretest probability of permanent GHD.
2019年美国临床内分泌医师协会指南建议，在过渡期诊断永久性生长激素缺乏症（GHD）时，胰高血糖素试验（GST）的生长激素峰值临界值≤3 μg/L和≤1 μg/L。
本研究旨在评估与胰岛素耐量试验（ITT）相比，GST在成年身高达成时定义GHD的准确性。
97例儿童期起病的GHD患者（中位年龄17.39岁）接受了ITT、GST和胰岛素样生长因子-1（IGF-1）检测；44例为特发性（孤立性GHD），35例为中度器质性GHD（0-2种激素缺乏），18例为重度器质性GHD（≥3种激素缺乏）。
布兰德和奥特曼分析显示，ITT和GST后生长激素峰值测量具有高度一致性。受试者工作特征分析确定，GST的最佳生长激素峰值临界值为7.3 μg/L[95%置信区间（CI）4.15-8.91；敏感性95.7%，特异性88.2%，阳性预测值（PPV）88.0%，阴性预测值（NPV）95.7%]，能够正确分类整个队列的91.8%，而5.8 μg/L是能够正确分类91.4%中度器质性GHD患者的最佳生长激素峰值临界值（95%CI 3.16-7.39；敏感性96.0%，特异性80.0%，PPV 92.3%，NPV 88.9%）。≥3种激素缺乏的患者在ITT时生长激素峰值<5 μg/L，在GST时<5.8 μg/L，但1例除外。IGF-1的最佳临界值为-1.4标准差评分（95%CI -1.94至0.77；敏感性75%，特异性94%，PPV 91.7%，NPV 81.0%），能够正确分类85.1%的研究人群。
对于儿童期起病且永久性GHD预测试概率高的年轻成年人，GST的生长激素峰值<5.8 μg/L是一个准确的诊断临界值。
