Congenital hyperinsulinism
Congenital hyperinsulinism
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DOI：
10.1016/j.earlhumdev.2010.05.003
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发表时间：
2010-05-01
影响因子：
2.5
通讯作者：
Nihoul-Fekete, Claire
中科院分区：
文献类型：
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作者：
Arnoux, Jean-Baptiste;de Lonlay, Pascale;Nihoul-Fekete, Claire
先天性高胰岛素血症(CHI或HI)是一种由于胰岛β细胞不适当地分泌胰岛素而导致反复低血糖的疾病。Hi有两个主要特征：纠正低血糖的高糖需求和对外源性高血糖素的低血糖反应。HI通常是孤立的，但可能很少是遗传综合征(如Beckwith-Wiedemann综合征、Sotos综合征等)的一部分。HI的严重程度是通过维持正常血糖所需的葡萄糖给药率和对治疗的反应性来评估的。新生儿起病的HI通常是严重的，而晚发型和综合征性HI通常对药物治疗有反应。血糖必须维持在正常范围内，以避免脑损伤，首先使用葡萄糖注射和胰高血糖素输注，然后在诊断确定后，进行特定的HI治疗。口服二氮卓是一线治疗方法。在治疗无效的情况下，可加用生长抑素类似物和钙拮抗剂，并进行进一步的组织学诊断：胰腺F-18-氟-L-多巴-正电子发射计算机断层扫描和分子分析。事实上，局灶型由胰岛细胞的局灶性腺瘤性增生组成，可在部分胰腺切除后治愈。弥漫性HI累及整个胰腺的所有胰岛β细胞。对药物(奥曲肽、二氮卓、钙拮抗剂和持续喂养)耐药的弥漫性HI可能需要行胰腺次全切除术，手术后的结果是不可预测的。局灶性胰岛细胞增生症的遗传学与ABCC8或KCNJ11基因的父系遗传突变有关，在增生性胰岛细胞中，母系等位基因的丢失具有特异性。弥漫性分离HI的遗传学是异质性的，可能是隐性遗传(ABCC8和KCNJ11)，也可能是显性遗传(ABCC8、KCNJ11、GCK、GLUD1、SLC16A1、HNF4a和HADH)。症状性HI多为弥漫型，其遗传学以证候为主。除钾通道缺陷引起的HI外(ABCC8和KCNJ11)。这些HI中的大多数对二氮嗪敏感。要点总结了HI的处理：i)通过血糖正常化来预防脑损伤和ii)筛查局灶性HI，因为它们可能在有限的胰腺切除后最终治愈。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
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 F-18-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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.