Thornton Paul S, Stanley Charles A, De Leon Diva D
Congenital Hyperinsulinism Center, Cook Children's Medical Center, Fort Worth, Texas, USA.
Congenital Hyperinsulinism Center, Division of Endocrinology and Diabetes, Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Horm Res Paediatr. 2022;95(6):631-637. doi: 10.1159/000526442. Epub 2022 Nov 29.
Congenital hyperinsulinism is the most common cause of persistent hypoglycemia in neonates, infants, and children. Since the first case descriptions in the 1950s, the field has advanced significantly. It was the development of the insulin radioimmunoassay by Yalow and Berson a decade later that made it possible to demonstrate that this form of persistent hypoglycemia was caused by insulin, and a few years later, Drash described the successful treatment of children with hyperinsulinism with the antihypertensive diazoxide, which until today remains the only approved treatment for hyperinsulinism. In the mid 1970s, Baker and Stanley described that hyperinsulinism can be recognized by inappropriate responses of metabolic fuels and hormones during the course of a provocative fasting challenge. Later, advances in molecular genetics led to the discovery of the different genetic subtypes of hyperinsulinism. One of the most impactful discoveries in the field was the recognition of the focal form of hyperinsulinism and the development of 18F-DOPA PET for the localization of focal lesions before surgery which has resulted in the possibility of cure for children with focal disease. However, treatment options for children with nonfocal diazoxide-unresponsive hyperinsulinism have continued to be limited. New drug development programs for hyperinsulinism promise to change this in the next few years. Unfortunately, despite all these advances, children with hyperinsulinism around the world continue to experience neurological sequelae at high rates, highlighting the importance of early diagnosis and effective treatment.
先天性高胰岛素血症是新生儿、婴儿和儿童持续性低血糖最常见的病因。自20世纪50年代首次描述该病例以来，该领域已取得显著进展。十年后Yalow和Berson开发了胰岛素放射免疫测定法，才得以证明这种持续性低血糖是由胰岛素引起的。几年后，Drash描述了用抗高血压药物二氮嗪成功治疗高胰岛素血症患儿的案例，直至今日，二氮嗪仍是唯一获批用于治疗高胰岛素血症的药物。20世纪70年代中期，Baker和Stanley描述了在激发性禁食试验过程中，高胰岛素血症可通过代谢燃料和激素的不适当反应来识别。后来，分子遗传学的进展导致发现了高胰岛素血症的不同基因亚型。该领域最具影响力的发现之一是认识到局灶性高胰岛素血症，并开发了用于术前局灶性病变定位的18F-DOPA PET，这使得局灶性疾病患儿有可能治愈。然而，对于非局灶性、对二氮嗪无反应的高胰岛素血症患儿，治疗选择仍然有限。高胰岛素血症的新药开发计划有望在未来几年改变这种状况。不幸的是，尽管取得了所有这些进展，但世界各地的高胰岛素血症患儿仍有很高比例出现神经后遗症，这凸显了早期诊断和有效治疗的重要性。
