Hospital Necker-Enfants Malades, Paris, France.
Early Hum Dev. 2010 May;86(5):287-94. doi: 10.1016/j.earlhumdev.2010.05.003. Epub 2010 Jun 13.
Congenital hyperinsulinism (CHI or HI) is a condition leading to recurrent hypoglycemia due to an inappropriate insulin secretion by the pancreatic islet beta cells. HI has two main characteristics: a high glucose requirement to correct hypoglycemia and a responsiveness of hypoglycemia to exogenous glucagon. HI is usually isolated but may be rarely part of a genetic syndrome (e.g. Beckwith-Wiedemann syndrome, Sotos syndrome etc.). The severity of HI is evaluated by the glucose administration rate required to maintain normal glycemia and the responsiveness to medical treatment. Neonatal onset HI is usually severe while late onset and syndromic HI are generally responsive to a medical treatment. Glycemia must be maintained within normal ranges to avoid brain damages, initially with glucose administration and glucagon infusion then, once the diagnosis is set, with specific HI treatment. Oral diazoxide is a first line treatment. In case of unresponsiveness to this treatment, somatostatin analogues and calcium antagonists may be added, and further investigations are required for the putative histological diagnosis: pancreatic (18)F-fluoro-L-DOPA PET-CT and molecular analysis. Indeed, focal forms consist of a focal adenomatous hyperplasia of islet cells, and will be cured after a partial pancreatectomy. Diffuse HI involves all the pancreatic beta cells of the whole pancreas. Diffuse HI resistant to medical treatment (octreotide, diazoxide, calcium antagonists and continuous feeding) may require subtotal pancreatectomy which post-operative outcome is unpredictable. The genetics of focal islet-cells hyperplasia associates a paternally inherited mutation of the ABCC8 or the KCNJ11 genes, with a loss of the maternal allele specifically in the hyperplasic islet cells. The genetics of diffuse isolated HI is heterogeneous and may be recessively inherited (ABCC8 and KCNJ11) or dominantly inherited (ABCC8, KCNJ11, GCK, GLUD1, SLC16A1, HNF4A and HADH). Syndromic HI are always diffuse form and the genetics depend on the syndrome. Except for HI due to potassium channel defect (ABCC8 and KCNJ11), most of these HI are sensitive to diazoxide. The main points sum up the management of HI: i) prevention of brain damages by normalizing glycemia and ii) screening for focal HI as they may be definitively cured after a limited pancreatectomy.
先天性高胰岛素血症 (CHI 或 HI) 是一种由于胰岛β细胞分泌不当胰岛素而导致反复低血糖的疾病。HI 有两个主要特征：纠正低血糖需要高葡萄糖需求和对外源胰高血糖素的反应性。HI 通常是孤立的，但也可能很少是遗传综合征的一部分（例如 Beckwith-Wiedemann 综合征、Sotos 综合征等）。HI 的严重程度通过纠正低血糖所需的葡萄糖给药率和对药物治疗的反应性来评估。新生儿期 HI 通常严重，而迟发性和综合征性 HI 通常对药物治疗有反应。必须将血糖维持在正常范围内，以避免脑损伤，最初通过葡萄糖给药和胰高血糖素输注，然后一旦确定诊断，就使用特定的 HI 治疗。口服二氮嗪是一线治疗方法。如果对此治疗无反应，可以添加生长抑素类似物和钙拮抗剂，并且需要进一步调查潜在的组织学诊断：胰腺（18）F-氟-L-DOPA PET-CT 和分子分析。实际上，局灶性形式由胰岛细胞的局灶性腺瘤性增生组成，部分胰腺切除术后可治愈。弥漫性 HI 涉及整个胰腺的所有胰岛β细胞。弥漫性 HI 对药物治疗（奥曲肽、二氮嗪、钙拮抗剂和持续喂养）无反应，可能需要进行次全胰腺切除术，术后结果不可预测。局灶性胰岛细胞增生的遗传学与 ABCC8 或 KCNJ11 基因的父系遗传突变相关，母系等位基因特异性缺失仅发生在增生的胰岛细胞中。弥漫性孤立 HI 的遗传学是异质性的，可能是隐性遗传（ABCC8 和 KCNJ11）或显性遗传（ABCC8、KCNJ11、GCK、GLUD1、SLC16A1、HNF4A 和 HADH）。综合征性 HI 总是弥漫性形式，遗传学取决于综合征。除了由于钾通道缺陷（ABCC8 和 KCNJ11）引起的 HI 外，大多数 HI 对二氮嗪敏感。要点总结了 HI 的管理：i）通过正常化血糖预防脑损伤和 ii）筛查局灶性 HI，因为它们在有限的胰腺切除术后可能被彻底治愈。
