Department of Endocrinology & Diabetes, Cork University Hospital, Cork, Ireland.
Principal Clinical Biochemist, Department of Biochemistry, Cork University Hospital, Cork, Ireland.
BMC Endocr Disord. 2022 Oct 27;22(1):262. doi: 10.1186/s12902-022-01175-4.
Non-islet cell tumour hypoglycemia (NICTH) is rarely encountered in clinical practice. Insulin-like growth factor 2 (IGF2) is the most common cause of NICTH observed in the setting of mesenchymal and epithelial neoplasia. This is a paraneoplastic syndrome caused by IGF2 activation of the insulin receptor.
An 80 year old female presented with a short history of recurrent episodes of confusion with laboratory confirmed hypoglycemia with a plasma glucose of 2.7 mmol/L on fasting which fulfilled Whipple's triad. Diagnostic clues to the aetiology at presentation include the fasting pattern of hypoglycemia, hypokalaemia and the absence of weight gain. A 72 hour fast with results showed early hypoglycemia and suppression of serum insulin, c-peptide, and proinsulin. Serum insulin antibody was not detected. Subsequent measurement of the serum IGF2:IGF1 ratio was elevated at 22.3 and consistent with IGF-2 mediated hypoglycemia and imaging studies demonstrated a pelvic mass. Dietary intervention and oral prednisolone abated hypoglycemia prior to surgery. Ultimately, hypoglycemia resolved following operative intervention and steroid therapy was successfully withdrawn. Histopathology was remarkable for dual neoplastic processes with uterine solitary fibrous tumour (SFT) confirmed as the source of IGF2 hypersecretion on IGF-2 immunohistochemistry and a coincidental invasive high grade serous carcinoma involving the fimbria of the right fallopian tube.
The paradox in this case is that the benign solitary fibrous tumour accounted for patient morbidity through secretion of IGF2 and without treatment, posed a mortality risk. This is despite the synchronous presence of a highly malignant fallopian tube neoplasm. This case reinforces the need for thorough clinical evaluation of hypoglycemia to allow prompt and definitive management.
非胰岛细胞瘤性低血糖症（NICTH）在临床实践中很少见。胰岛素样生长因子 2（IGF2）是在间叶性和上皮性肿瘤中观察到的 NICTH 的最常见原因。这是一种副肿瘤综合征，由 IGF2 激活胰岛素受体引起。
一名 80 岁女性因反复发作性意识模糊就诊，实验室检查证实空腹时出现低血糖，血糖为 2.7mmol/L，符合 Whipple 三联征。发病时病因的诊断线索包括空腹性低血糖、低钾血症和体重无增加。72 小时禁食试验结果显示早期低血糖和血清胰岛素、C 肽和胰岛素原抑制。未检测到血清胰岛素抗体。随后测量血清 IGF2：IGF1 比值升高至 22.3，与 IGF-2 介导的低血糖一致，影像学检查显示盆腔肿块。饮食干预和口服泼尼松可在手术前减轻低血糖。最终，手术干预后低血糖得到缓解，类固醇治疗成功停药。组织病理学表现为双重肿瘤过程，子宫孤立性纤维瘤（SFT）在 IGF-2 免疫组化中证实为 IGF2 分泌过多的来源，同时伴有右侧输卵管伞部浸润性高级别浆液性癌。
本例的矛盾之处在于良性孤立性纤维瘤通过分泌 IGF2 导致患者发病，且没有得到治疗，存在死亡风险。尽管同时存在高度恶性的输卵管肿瘤。这个病例强调了需要对低血糖进行彻底的临床评估，以便及时和明确的管理。
