Hyperinsulinemic hypoglycemia (HH) of pancreatic origin includes congenital hyperinsulinism (CHI), insulinoma, insulinomatosis, and adult-onset non-insulinoma persistent hyperinsulinemic hypoglycemia syndrome (NI-PHHS). In this review, we describe the genotype-histotype-phenotype correlations in HH and their therapeutic implications. CHI can occur from birth or later on in life. Histologically, diffuse CHI shows diffuse beta cell hypertrophy with a few giant nuclei per islet of Langerhans, most frequently caused by loss-of-function mutations in ABCC8 or KCNJ11. Focal CHI is histologically characterized by focal adenomatous hyperplasia consisting of confluent hyperplastic islets, caused by a paternal ABCC8/KCNJ11 mutation combined with paternal uniparental disomy of 11p15. CHI in Beckwith-Wiedemann syndrome is caused by mosaic changes in the imprinting region 11p15.4-11p15.5, leading to segmental or diffuse overgrowth of endocrine tissue in the pancreas. Morphological mosaicism of pancreatic islets is characterized by occurence of hyperplastic (type 1) islets in one or a few lobules and small (type 2) islets in the entire pancreas. Other rare genetic causes of CHI show less characteristic or unspecific histology. HH with a predominant adult onset includes insulinomas, which are pancreatic insulin-producing endocrine neoplasms, in some cases with metastatic potential. Insulinomas occur sporadically or as part of multiple endocrine neoplasia type 1 due to MEN1 mutations. MAFA mutations may histologically lead to insulinomatosis with insulin-producing neuroendocrine microadenomas or neuroendocrine neoplasms. NI-PHHS is mainly seen in adults and shows slight histological changes in some patients, which have been defined as major and minor criteria. The genetic cause is unknown in most cases. The diagnosis of HH, as defined by genetic, histological, and phenotypic features, has important implications for patient management and outcome.

中文翻译：

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高胰岛素性低血糖的基因型-组织型-表型相关性。

胰腺源性高胰岛素性低血糖（HH）包括先天性高胰岛素血症（CHI）、胰岛素瘤、胰岛素瘤病和成人发病的非胰岛素瘤持续性高胰岛素性低血糖综合征（NI-PHHS）。在这篇综述中，我们描述了 HH 的基因型-组织型-表型相关性及其治疗意义。 CHI 可以从出生时或晚年发生。组织学上，弥漫性 CHI 显示弥漫性 β 细胞肥大，每个朗格汉斯岛有几个巨大的细胞核，最常见的是由ABCC8或KCNJ11 的功能丧失突变引起。局灶性 CHI 的组织学特征是局灶性腺瘤性增生，由融合的增生性胰岛组成，由父系ABCC8/KCNJ11突变与父系单亲二体性 11p15 相结合引起。 Beckwith-Wiedemann 综合征中的 CHI 是由印记区域 11p15.4-11p15.5 的镶嵌变化引起的，导致胰腺内分泌组织节段性或弥漫性过度生长。胰岛形态嵌合的特征是在一个或几个小叶中出现增生（1 型）胰岛，在整个胰腺中出现小（2 型）胰岛。 CHI 的其他罕见遗传原因表现出较少特征性或非特异性组织学。以成人为主的 HH 包括胰岛素瘤，这是一种产生胰岛素的胰腺内分泌肿瘤，在某些情况下具有转移潜力。由于MEN1突变，胰岛素瘤偶尔发生或作为 1 型多发性内分泌肿瘤的一部分发生。MAFA突变可能在组织学上导致胰岛素瘤病，伴有产生胰岛素的神经内分泌微腺瘤或神经内分泌肿瘤。 NI-PHHS主要见于成人，部分患者表现出轻微的组织学改变，已被定义为主要和次要标准。在大多数情况下，遗传原因尚不清楚。根据遗传、组织学和表型特征定义的 HH 诊断对患者管理和结果具有重要意义。