Abstract: Objective To analyze the differences in clinical indicators between malignant insulinoma and benign insulinoma, in order to provide diagnostic and therapeutic insights for the early detection and diagnosis of malignant insulinoma. Methods A retrospective analysis was conducted in patients diagnosed and treated for insulinoma at Peking Union Medical College Hospital from January 2018 to June 2022. Among them,10 cases were diagnosed as malignant insulinoma. Twenty cases of benign insulinoma patients matched for age, sex, and body mass index (BMI), were randomly selected. Statistical analysis was performed to compare the differences between malignant and benign insulinomas. Results 1)Compared to benign insulinoma, malignant insulinoma showed significantly elevated C-peptide (CP) and C-peptide to glucose ratio (CPGlu) during hypoglycemia (blood glucose＜3.0 mmol/L) [6.04 (3.40, 6.76) vs 1.68(1.39, 2.47)ng/mL, P＜0.05), 2.25(1.12, 3.58) vs 0.74 (0.54, 1.54), P＜0.05]. The tumor diameter (DIA) was larger (1.9±0.6 vs 1.4±0.3 cm, P＜0.05), and the insulin level at 300 minutes (INS300) during the 5-hour oral glucose tolerance test (5 h OGTT) was significantly elevated(30.47±5.67 vs 9.67 ± 3.32) μIU/mL, P＜0.01). Levels of blood tumor markers AFP, CEA, and CA724 were also increased (P＜0.05). 2)Correlation analysis indicated that CP, CPGlu, DIA, INS300, AFP, CEA, and CA724 were positively correlated with malignant insulinoma during hypoglycemia. 3)The ROC curve analysis suggested that the optimal cut-off points for distinguishing malignant from benign insulinomas were CP 2.49 ng/mL, CPGlu 1.31, DIA 1.85 cm, and INS300 20.22 μIU/mL, respectively. Conclusions In clinical practice, if an insulinoma patient has a CP level higher than 2.49 ng/mL and a tumor diameter larger than 1.9 cm during hypoglycemia, the possibility of malignant insulinoma should be considered, warranting further examinations and enhanced follow-up. Persistent elevation of AFP, CEA, and CA724 may indicate malignant insulinoma.

Key words: malignant insulinoma, benign insulinoma, clinical indicators, 5 h oral glucose tolerance test, tumor markers