Objective:

To evaluate the diagnostic performance of the insulin-to-C-peptide molar ratio for distinguishing insulin autoimmune syndrome (IAS) and exogenous insulin antibody syndrome (EIAS) from insulinoma and to identify the optimal diagnostic cutoff.

Approach:

• Study Design: Retrospective collection of clinical and biochemical data from patients with IAS, EIAS, and insulinoma.
• Data Analysis: Receiver-operating-characteristic (ROC) curve analysis was performed to assess diagnostic performance.

Key Findings:

• The insulin-to-C-peptide molar ratio was significantly higher in IAS and EIAS than in insulinoma during fasting and hypoglycemic episodes.
• During hypoglycemic episodes, the AUC was 0.970 for IAS versus insulinoma and 0.944 for EIAS versus insulinoma.
• Optimal cutoffs were identified as 0.382 for IAS and 0.552 for EIAS during hypoglycemic episodes.
• In the fasting state, AUCs were 0.916 for IAS and 0.961 for EIAS, with optimal cutoffs of 0.309 and 0.386, respectively.
• Insulin concentration alone also showed good diagnostic performance for distinguishing IAS from insulinoma, with AUCs of 0.985 and 0.943 during hypoglycemic episodes and in the fasting state, respectively.
• Compared with the conventionally used cutoff of 1, the optimal cutoffs substantially improved sensitivity while maintaining high specificity.

Interpretation:

The insulin-to-C-peptide molar ratio shows good diagnostic performance for distinguishing IAS and EIAS from insulinoma, with lower cutoffs providing better sensitivity.

Limitations:

• The study is retrospective and may be limited by sample size.
• Validation in larger cohorts is needed to confirm findings.

Conclusion:

The insulin-to-C-peptide molar ratio is a useful diagnostic tool for differentiating IAS and EIAS from insulinoma, with lower cutoffs potentially enhancing diagnostic accuracy.