Breil Thomas, Kneppo Carolin, Bettendorf Markus, Müller Hermann L, Kapelari Klaus, Schnabel Dirk, Woelfle Joachim
Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, University Hospital Heidelberg, Heidelberg, Germany.
Department of Paediatrics and Paediatric Haematology/Oncology, Klinikum Oldenburg AöR, Medical Campus University Oldenburg, Oldenburg, Germany.
J Pediatr Endocrinol Metab. 2018 Aug 28;31(8):895-902. doi: 10.1515/jpem-2018-0139.
Background Recombinant human insulin-like growth factor 1 (rhIGF-I) has been approved as an orphan drug for the treatment of growth failure in children and adolescents with severe primary IGF-I deficiency (SPIGFD) with little pharmacokinetic data available. Therefore, sequential measurements of serum IGF-I, glucose, potassium, insulin and cortisol were performed in patients treated with rhIGF-I to evaluate their significance in safety and efficacy. Methods Repetitive blood samples were taken after meals before and 30, 60, 120, 180 and 360 min after rhIGF-I injections in two male patients with Laron syndrome at times of dose adjustments. Results Maximal IGF-I concentrations were observed 2 h after injections (495 ng/mL) and concentrations were still higher 6 h after injections than at baseline (303 ng/mL vs. 137 ng/mL). Thirteen percent of all and 33% of maximum IGF-I concentrations were greater than +2 standard deviation score (SDS) calculated for bone age (BA) (IGF-I SDS BA) rather than chronological age (CA) as BA was significantly delayed to CA by 3.2 years (p=0.0007). Height velocities correlated with individual maximum IGF-I SDS BA (ρ=0.735; p<0.0001). Serum insulin, cortisol and glucose did not correlate with IGF-I concentrations, but serum potassium showed a negative correlation (ρ=-0.364; p<0.0001) with IGF-I concentrations. Conclusions Sequential measurements of serum IGF-I, glucose and potassium in patients with Laron syndrome may aid in optimizing and individualizing rhIGF-I treatment. IGF-I concentrations should be referenced according to BA which better reflects the biological age. The inverse correlation of IGF-I and serum potassium concentrations after injections of rhIGF-I has not been reported before and warrants further consideration.
背景 重组人生长激素（rhIGF-I）已被批准作为孤儿药用于治疗患有严重原发性IGF-I缺乏症（SPIGFD）的儿童和青少年生长发育迟缓，目前几乎没有可用的药代动力学数据。因此，对接受rhIGF-I治疗的患者进行血清IGF-I、葡萄糖、钾、胰岛素和皮质醇的连续测量，以评估它们在安全性和有效性方面的意义。方法 在两名患有拉伦综合征的男性患者调整剂量时，于餐后、rhIGF-I注射前以及注射后30、60、120、180和360分钟采集重复血样。结果 注射后2小时观察到IGF-I浓度最高（495 ng/mL），且注射后6小时的浓度仍高于基线（303 ng/mL对137 ng/mL）。所有IGF-I浓度的13%以及最大IGF-I浓度的33%大于根据骨龄（BA）而非实际年龄（CA）计算的+2标准差评分（SDS）（IGF-I SDS BA），因为骨龄比实际年龄显著延迟3.2岁（p = 0.0007）。身高增长速度与个体最大IGF-I SDS BA相关（ρ = 0.735；p < 0.0001）。血清胰岛素、皮质醇和葡萄糖与IGF-I浓度无关，但血清钾与IGF-I浓度呈负相关（ρ = -0.364；p < 0.0001）。结论 对拉伦综合征患者进行血清IGF-I、葡萄糖和钾的连续测量可能有助于优化和个体化rhIGF-I治疗。IGF-I浓度应根据能更好反映生物学年龄的骨龄来参考。rhIGF-I注射后IGF-I与血清钾浓度的负相关此前未见报道，值得进一步研究。
