Clinical Presentation, Diagnosis, and Management of Hyperinsulinemic Hypoglycemia in Adults: A Single-center Experience

Introduction: Hyperinsulinemic Hypoglycemia (HH) is a rare condition characterized by inappropriately elevated insulin levels in the presence of low glucose levels. A proper diagnostic framework is fundamental to avoid patients undergoing unnecessary diagnostic and therapeutic invasive procedures. Objective: The study aimed to assess the clinical presentation, diagnostic work-up, and treatment of a single-center cohort of patients affected by HH. Methods: We conducted a retrospective analysis of data collected from January 2000-2023 Results: Our study included 104 patients: 81 (58% F) affected by insulinoma, 11 (91% F) by autoimmune hypoglycemia, 7 (71% M) by post-gastric surgery hypoglycemia, and 5 (80% F) by factitious hypoglycemia. HH was more frequent in females (63 F vs. 41 M, p-value 0.039). The median age at diagnosis was lower in insulinoma than in the autoimmune group (52.7 vs. 63.7 y, p < 0.001). During the hypoglycemic event, insulin and C-peptide levels were significantly higher in autoimmune hypoglycemia than in insulinoma (insulin 324.6 vs. 36.4 μU/ml, p-value 0.033; C-peptide 14.25 vs. 3.99 ng/ml, p-value 0.003). Specifically, C-peptide levels < 9.6 ng/ml and insulin levels < 75 μU/ml exhibited 97.3% vs. 93.4% sensitivity and 80% vs. 90% specificity for insulinoma diagnosis, respectively. Regarding insulinoma, the sensitivity of localizing imaging was 88% for Endoscopic Ultrasound (EUS), 86% for Magnetic Resonance Imaging (MRI), 82% for Computed Tomography (CT) scan, 52% for nuclear imaging, and 100% for angiography with the Doppman test. Among insulinoma patients, 79% received surgical treatment while 4% radiofrequency ablation. Symptomatic remission occurred in 100% of cases. Conclusion: We have confirmed insulinoma as the primary cause of HH. The autoimmune form should be suspected when insulin and C-peptide levels are markedly elevated.