Abstract

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-therapeutic invasive procedures.

Objective: 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, 5 (80% F) by factitious hypoglycemia. HH was more frequent in females (63 F vs 41 M, pvalue 0.039). The median age at diagnosis was lower in insulinoma than in 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 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 had respectively 97.3% vs 93.4% sensitivity and 80% vs 90% specificity for insulinoma diagnosis. Regarding insulinoma, the sensitivity of localizing imaging was 88% for EUS, 86% for MRI, 82% for CT scan, 52% for nuclear imaging and 100% for angiography with Doppman test. Among insulinoma patients 79% received surgical treatment while 4% radiofrequency ablation. Symptomatic remission occurred in 100% of cases.

Conclusion: We confirmed insulinoma as the primary cause of HH. The autoimmune form should be suspected when insulin and cpeptide levels are markedly elevated.