Ryan Tyler J, Raj Nitya, Reidy Diane, Goncalves Marcus D, Flory James H
Division of Endocrinology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Weill Cornell Medicine, New York, New York.
AACE Endocrinol Diabetes. 2025 Apr 10;12(1):2-7. doi: 10.1016/j.aed.2025.03.010. eCollection 2025 May-Jun.
BACKGROUND/OBJECTIVE: Tumor-induced hypoglycemia (TIH) is a rare and often fatal complication of cancers that produce or induce secretion of hormones such as insulin, insulin-like growth factor 2, and proinsulin. We present a case series describing the effectiveness and tolerability of the phosphatidylinositol 3-kinase inhibitor alpelisib in 2 women with metastatic insulin-producing or proinsulin-producing tumors.
Over 4 to 8 months of follow-up, it was observed that alpelisib resulted in reductions in hypoglycemic rates (<54 mg/dL) as assessed on continuous glucose monitoring. For the first patient, the proportion of glucose readings <54 mg/dL fell from 2.3% (95% CI, 2.1-2.4) to 0.2% (95% CI, 0.2%-0.3%), and the rate ratio was 0.087 (95% CI, 0.086-0.089). For the second patient, the proportion of low glucose readings fell from 9.0% (95% CI, 8.6-9.4) to 2.0% (95% CI, 2.2%-2.5%), and the rate ratio was 0.26 (95% CI, 0.26-0.27). Alpelisib was not associated with significant adverse events. There was one instance of gastrointestinal bleeding that was likely not attributable to alpelisib. Due to high cost and off-label use, the process of obtaining alpelisib was complex and took several months for the first patient and 2 years for the second patient.
Treatment options for TIH are limited. Alpelisib, a small-molecule phosphatidylinositol 3-kinase inhibitor, may blunt the hypoglycemic effect of excess insulin and proinsulin by decreasing glucose transport and increasing glycogenolysis and gluconeogenesis.
Alpelisib appears to be effective and well tolerated for long-term treatment of TIH.
背景/目的：肿瘤诱导的低血糖症（TIH）是一种罕见且常致命的癌症并发症，这些癌症会产生或诱导胰岛素、胰岛素样生长因子2和胰岛素原等激素的分泌。我们报告了一个病例系列，描述了磷脂酰肌醇3激酶抑制剂阿培利司对2例转移性胰岛素分泌或胰岛素原分泌肿瘤女性患者的有效性和耐受性。
在4至8个月的随访中，通过持续葡萄糖监测观察到阿培利司可降低低血糖发生率（<54mg/dL）。对于首例患者，血糖读数<54mg/dL的比例从2.3%（95%CI，2.1 - 2.4）降至0.2%（95%CI，0.2% - 0.3%），率比为0.087（95%CI，0.086 - 0.089）。对于第二例患者，低血糖读数的比例从9.0%（95%CI，8.6 - 9.4）降至2.0%（95%CI，2.2% - 2.5%），率比为0.26（95%CI，0.26 - 0.27）。阿培利司未引起显著不良事件。有1例胃肠道出血，可能与阿培利司无关。由于成本高且为非适应证用药，获取阿培利司的过程复杂，首例患者花费数月，第二例患者花费2年。
TIH的治疗选择有限。阿培利司是一种小分子磷脂酰肌醇3激酶抑制剂，可能通过减少葡萄糖转运、增加糖原分解和糖异生来减轻过量胰岛素和胰岛素原的低血糖作用。
阿培利司似乎对TIH的长期治疗有效且耐受性良好。
