摘要
非胰島細胞腫瘤性低血糖（non-islet cell tumor hypoglycemia; NICTH）泛指由胰島細胞瘤之外的其他腫瘤引起的低血糖症。雖然臨床上較少見，但是腫瘤伴生症（paraneoplastic syndrome）相關的低血糖併發症卻會造成危及生命的問題。這些非胰島細胞腫瘤（non-islet cell tumor）主要發生在惡性腫瘤中，但也有一些良性巨大腫瘤可以導致NICTH。間質細胞和上皮細胞為最常見的組織細胞形態，前者以單發性纖維瘤及間皮瘤較為常見，血管外皮細胞瘤次之。後者則以肝細胞癌最為多見。過去，NICTH的發生認為是由於腫瘤消耗過多糖份而引起，但多年來的研究結果顯示，腫瘤組織分泌大分子量的第二型類胰島素生長因子（macromolecules insulin-like growth factor-II; big IGF-II）才是發生的主要原因。它是IGF-II形成過程中裂解不完全的前體蛋白，在人體主要是與IGF結合蛋白（IGF binding proteins; IGFBPs）形成小分子的複合物或游離形式存在。其容易穿過血管內皮進入組織中與胰島素受器結合，導致患者低血糖發作。診斷要件除了符合Whipple's triad外，實驗室檢查尚可發現在低血糖時血液中big IGF-II的濃度及IGF-II/IGF-I比率增加（＞3），而胰島素、C-peptide及β-hydroxybutyrate濃度卻是呈現低下的現象。臨床上可就胸、腹與骨盆腔施行傳統的影像學、核醫掃描或氟-18去氧葡萄糖正子造影（FDG-PET）檢查並進行腫瘤定位。目前，手術完整切除是最有效的療法。如無法進行手術，應以緩解低血糖為主要目標，包括滴注葡萄糖溶液，給予糖皮質素、升糖素或人類重組生長素。
並列摘要
Non-islet cell tumor hypoglycemia (NICTH) is an exceptional rare but critical para-neoplastic complication. It mainly occurs in patient with malignancy or some other large benign solid tumors. Tumors of mesenchymal or hepatic origin are most commonly reported with solitary fibrous tumor and/or mesothelioma, hemangiopericytoma and hepatocellular carcinoma in that sequence. Massive tumor burden with glucose consumption may be considered as the cause of hypoglycemia before. However, recent studies have demonstrated that excessive production of the big-IGF-II or incompletely processing IGF-II precursors (pro-IGF-II) by tumor is the main etiology of hypoglycemia. Tumor-derived big IGF-II primarily forms smaller complexes with IGF binding proteins to increase serum concentration of the free, unbound IGFs, which can easily cross the capillary membrane to act on insulin receptors leading to hypoglycemia. Diagnosis of the NICTH includes typical symptom/sign fulfilled with Whipple's triad of hypoglycemia, high level of serum big IGF-II, high ratio of IGF-II / IGF-I (＞3), low levels of serum insulin, C-peptide and β-hydroxybutyrate. Tumor localization, focusing chest, abdomen or pelvis, is suggested to detect by conventional radiologic imaging, fluorodeoxyglucose-positron emission tomography or radionuclide scan. The most effective therapeutic strategy for NICTH is aimed for complete removal of the tumor or reduction of the tumor mass. Otherwise, alleviating hypoglycemia is substantially significant, when curative resection is no longer possible. The strategies include continuous administration of glucose, use of glucocorticoid, glucagon, or recombinant human growth hormone.