The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of GH1 or GHSR) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to GH1 variants) but less on the role of GHSR variants. Several genetic causes of (partial) GHI are known (GHR, STAT5B, STAT3, IGF1, IGFALS defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.
Horm Res Paediatr

中文翻译：

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生长激素分泌明显正常的矮小 IGF-I 缺陷儿童的鉴别诊断

在排除获得性原因后，目前对胰岛素样生长因子 I (IGF-I) 低且 GH 刺激试验 (GHST) 中生长激素 (GH) 峰值正常的矮小儿童的鉴别诊断包括以下疾病： (1) 与正常刺激的 GH 峰值相比，自发 GH 分泌减少（“GH 神经分泌功能障碍”，GHND）和 (2) 具有正常 GH 敏感性的遗传状况（例如，GH1或GHSR的致病性变异) 和 (3) GH 不敏感 (GHI)。我们对 GHND 的概念以及 12 小时或 24 小时 GH 曲线在选择接受 GH 治疗的儿童中的作用进行了批判性评估。健康儿童的平均 24 小时 GH 浓度与 GH 缺乏的儿童重叠，表明先前提出的临界值（3.0-3.2 μg/L）太高。执行 GH 曲线的主要优点是它可以防止大约 20% 的 GHST 假阳性测试结果，同时它还可以检测儿童的低自发 GH 分泌，根据刺激测试，这些儿童被认为 GH 足够。然而，由于患者和健康预算的巨大负担，GH 概况仅在少数中心使用。关于遗传原因，有充分证据表明存在 Kowarski 综合征（由于GH1变体），但较少讨论GHSR变体的作用。已知（部分）GHI 的几种遗传原因（GHR、STAT5B、STAT3、IGF1、IGFALS缺陷以及 Noonan 和 3M 综合征），其中一些对 GH 治疗有积极反应。在最后一部分，我们推测假设的原因。
儿科荷尔蒙