Supplementary Material for: Hypoglycemia in Children Referred to a Tertiary Care Pediatric Endocrine Clinic: Age-Dependent Etiological Variations

Introduction: Diagnosing hypoglycemia in infants and children presents significant challenges. Our objective was to elucidate the diagnoses and clinical features of children with hypoglycemia referred to a pediatric endocrine tertiary clinic.

Methods: Retrospective study of 154 children (0-18 years old) presenting with hypoglycemia, during 1992-2018.

Results: The cohort was divided by clinical diagnosis into six groups: ketotic hypoglycemia (n=45, 29.2%), congenital hyperinsulinemic hypoglycemia (n=35, 22.7%), transient hyperinsulinemic hypoglycemia (n=28, 18.2%), metabolic disorder (n=14, 9.1%), systemic disease/syndrome (n=15, 9.7%), and hormone deficiencies (n=8, 5.2%). Two patients had insulinoma and in 7 (4.5%) no diagnosis was elucidated. At diagnosis, 58 (37.7%) were <1 month old, 23 (14.9%) aged 1-12 months, 58 (37.7%) aged 1-6 years, and 15 (9.7%) aged 6-18 years. Hypoglycemia etiology varied among neonates, infants, and children. In eight patients hypoglycemia was asymptomatic. Of 47 patients who completed a diagnostic fast, 31 became hypoglycemic, yet a significant added value for diagnosis was only found in 14 (29.8%) patients.

Conclusions: Hypoglycemia etiology in children is heterogeneous and varies by age. Any hypoglycemia measured in a child should be seriously evaluated as 7% are asymptomatic. Work-up should be tailored based on age, and clinical, biochemical, and imaging findings. Despite extensive work-up, in a significant number of patients the mechanism underlying pediatric hypoglycemia remains an enigma. This emphasizes the unmet needs and challenges in studying pediatric hypoglycemia.

引言：婴幼儿低血糖（hypoglycemia）的临床诊断始终面临诸多严峻挑战。本研究旨在明确转诊至儿科内分泌三级诊疗中心的低血糖患儿的确诊类型与临床特征。
方法：本研究为回顾性研究，纳入1992年至2018年间收治的154例0~18岁低血糖患儿。
结果：依据临床诊断将本队列分为六组：酮症性低血糖（ketotic hypoglycemia，n=45，29.2%）、先天性高胰岛素血症性低血糖（congenital hyperinsulinemic hypoglycemia，n=35，22.7%）、短暂性高胰岛素血症性低血糖（transient hyperinsulinemic hypoglycemia，n=28，18.2%）、代谢紊乱（metabolic disorder，n=14，9.1%）、系统性疾病/综合征（systemic disease/syndrome，n=15，9.7%）以及激素缺乏症（hormone deficiencies，n=8，5.2%）。另有2例患儿确诊为胰岛素瘤（insulinoma），7例（4.5%）患儿未明确诊断。确诊时，58例（37.7%）患儿年龄小于1月龄，23例（14.9%）为1~12月龄，58例（37.7%）为1~6岁，15例（9.7%）为6~18岁。新生儿、婴幼儿及儿童的低血糖病因存在显著差异。8例患儿的低血糖无明显临床症状。47例完成诊断性禁食（diagnostic fast）的患儿中，31例出现低血糖发作，但仅14例（29.8%）的诊断通过该检查获得了显著增益。
结论：儿童低血糖的病因具有异质性，且随年龄不同而存在差异。由于7%的低血糖患儿无明显症状，因此对检测出低血糖的儿童均应进行全面评估。临床检查应根据患儿年龄、临床特征、生化及影像学结果进行个体化定制。尽管已开展了全面的检查评估，但仍有相当比例的儿科低血糖患儿的发病机制尚未明确。这凸显了当前儿科低血糖研究领域仍存在未被满足的需求与诸多挑战。