Flader Maciej, Zalas Dominika, Niedziela Marek
Department of Pediatric Endocrinology and Rheumatology, 2nd Chair of Pediatrics, Poznan University of Medical Sciences.
Pediatr Endocrinol Diabetes Metab. 2017;23(4):215-220. doi: 10.18544/PEDM-23.04.0096.
According to the growth hormone - insulin-like growth factor 1 axis (GH/IGF1 axis) theory, the actions of GH on promoting growth are mediated by IGF1. In the blood, IGF1, insulin-like growth factor 1 binding protein 3 (IGFBP3) and acid-labile subunit (ALS) form ternary complexes, hence the accumulation of IGF1. We report a case of 10-year-old male with short stature due to GH deficiency diagnosed with hypopituitarism. Therapy with recombinant human GH (rhGH) was initiated at 11 years and 4 months. After twenty three months on treatment clinical effects were as follows: increase in the patient's height by 19.2 cm (initial height 12.4 cm vs. 140.6 cm; hSDS -4.35 vs. -2.7; predicted adult height 176 cm vs. 182 cm, respectively). Despite good clinical response to the therapy, serum levels of IGF1 and IGFBP3 remained diminished: IGF1 - 28 ng/ml initially, vs. 23 ng/ml 19 months on therapy and IGFBP3 - 1116 ng/ml initially, vs. 1888 ng/ml after 11 months on therapy. We attempt to justify this phenomenon by reconsidering the IGF1-independent GH actions, assessing the endocrine role of hepatic IGF1 in comparison to the autocrine/paracrine role of its bone tissue fraction, and evaluating the functions of ALS. The exact explanation for the positive response to rhGH treatment without the expected increase in IGF1 in our patient remains unknown. Serum levels of IGF1 and IGFBP3 seem not always to be reliable markers of the response to rhGH treatment in GH-deficient patients.
根据生长激素-胰岛素样生长因子1轴（GH/IGF1轴）理论，GH促进生长的作用是由IGF1介导的。在血液中，IGF1、胰岛素样生长因子1结合蛋白3（IGFBP3）和酸不稳定亚基（ALS）形成三元复合物，从而使IGF1得以蓄积。我们报告一例10岁男性因生长激素缺乏导致身材矮小，诊断为垂体功能减退。11岁4个月时开始使用重组人生长激素（rhGH）治疗。治疗23个月后的临床效果如下：患者身高增加19.2厘米（初始身高124厘米，治疗后为140.6厘米；身高标准差评分分别为-4.35和-2.7；预测成人身高分别为176厘米和182厘米）。尽管治疗取得了良好的临床反应，但血清IGF1和IGFBP3水平仍持续降低：IGF1最初为28纳克/毫升，治疗19个月后为23纳克/毫升；IGFBP3最初为1116纳克/毫升，治疗11个月后为1888纳克/毫升。我们试图通过重新审视不依赖IGF1的GH作用、评估肝脏IGF1的内分泌作用与其骨组织部分的自分泌/旁分泌作用，并评估ALS的功能来解释这一现象。在我们的患者中，对rhGH治疗有阳性反应但IGF1未如预期增加的确切原因尚不清楚。在生长激素缺乏的患者中，血清IGF1和IGFBP3水平似乎并不总是rhGH治疗反应的可靠标志物。
