Division of Endocrinology, Instituto Nacional de Pediatria, Mexico City, Mexico.
Cook Children's Medical Center Congenital Hyperinsulinism Center, Fort Worth, TX, USA.
Paediatr Drugs. 2019 Jun;21(3):123-136. doi: 10.1007/s40272-019-00334-w.
Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycmia in neonatles and children. The inappropriate secretion of insulin by the pancreatic β-cells produces recurrent hypoglycemia, which can lead to severe and permanent brain damage. CHI results from mutations in different genes that play a role in the insulin secretion pathway, and each differs in their responsiveness to medical treatment. Currently, the only available approved treatment for hyperinsulinism is diazoxide. Patients unresponsive to diazoxide may benefit from specialized evaluation including genetic testing and 18F-DOPA PET to identify those with focal forms of CHI. The focal forms can be cured by selective pancreatectomy, but the management of diazoxide-unresponsive diffuse CHI is a real therapeutic challenge. Current off-label therapies include intravenous glucagon, octreotide and long-acting somatostatin analogs; however, they are often insufficient, and a 98% pancreatectomy or continuous feeds may be required. For the first time in over 40 years, new drugs are being developed, but none have made it to market yet. In this review, we will discuss current on-label and off-label drugs and review the currently available data on the novel drugs under development.
先天性高胰岛素血症（CHI）是新生儿和儿童持续性低血糖的最常见原因。胰腺β细胞不适当分泌胰岛素会导致反复发作的低血糖，从而导致严重且永久性的脑损伤。CHI 是由在胰岛素分泌途径中起作用的不同基因突变引起的，并且每种基因突变对药物治疗的反应都不同。目前，高胰岛素血症唯一可用的批准治疗方法是二氮嗪。对二氮嗪无反应的患者可能受益于专门的评估，包括基因检测和 18F-DOPA PET，以确定那些具有局灶性 CHI 的患者。局灶性 CHI 可以通过选择性胰腺切除术治愈，但对二氮嗪无反应的弥漫性 CHI 的管理是一个真正的治疗挑战。目前的非适应证治疗包括静脉内胰高血糖素、奥曲肽和长效生长抑素类似物；然而，这些治疗方法往往不够，可能需要进行 98%的胰腺切除术或持续喂养。40 多年来，首次开发了新的药物，但目前尚无一种药物上市。在这篇综述中，我们将讨论目前的适应证和非适应证药物，并回顾正在开发的新型药物的现有数据。
