Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Histol Histopathol. 2024 Jul;39(7):817-844. doi: 10.14670/HH-18-709. Epub 2024 Jan 12.
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 or . Focal CHI is histologically characterized by focal adenomatous hyperplasia consisting of confluent hyperplastic islets, caused by a paternal 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 mutations. 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.
胰腺源性高胰岛素血症性低血糖症（HH）包括先天性高胰岛素血症（CHI）、胰岛素瘤、胰岛素瘤病和成人起病的非胰岛素瘤性持续性高胰岛素血症低血糖综合征（NI-PHHS）。在本综述中，我们描述了 HH 中的基因型-组织型-表型相关性及其治疗意义。CHI 可发生于出生时或之后的任何时间。组织学上，弥漫性 CHI 表现为胰岛内散在的β细胞肥大，每个胰岛内有几个巨核，最常见于 或 功能丧失突变。局灶性 CHI 组织学上的特征是局灶性腺瘤样增生，由融合性增生胰岛组成，由父系 突变与 11p15 的父系单亲二倍体相结合引起。Beckwith-Wiedemann 综合征中的 CHI 是由 11p15.4-11p15.5 印迹区域的镶嵌性改变引起的，导致胰腺内分泌组织的节段性或弥漫性过度生长。胰岛的形态镶嵌性表现为一个或少数几个小叶中出现增生性（1 型）胰岛，而整个胰腺中存在小（2 型）胰岛。CHI 的其他罕见遗传原因表现出较少的特征性或非特异性组织学改变。以成人起病为主的 HH 包括胰岛素瘤，这是胰腺胰岛素产生的内分泌肿瘤，在某些情况下具有转移潜能。胰岛素瘤偶发或作为多发性内分泌肿瘤 1 型的一部分发生，与 突变有关。 突变可能在组织学上导致伴有胰岛素产生的神经内分泌微腺瘤或神经内分泌肿瘤的胰岛素瘤病。NI-PHHS 主要见于成人，一些患者有轻微的组织学改变，这些改变被定义为主要和次要标准。大多数情况下，其遗传原因尚不清楚。根据遗传、组织学和表型特征定义的 HH 诊断对患者的管理和预后具有重要意义。
