Discordant Timing of Hypoglycemic Agent Screening Causing Delayed Diagnosis of Sulfonylurea-Induced Hypoglycemia

Oral hypoglycemic agents are a frequent cause of hypoglycemia in nondiabetic people. Here, we report a case of recurrent hypoglycemia caused by glipizide, in which diagnosis was delayed because of a combination of delayed hypoglycemic agent screening and low sensitivity of the hypoglycemic agent screening panel used.

A 66-year-old woman repeatedly presented with symptomatic hypoglycemia. At the first presentation, the serum glucose level was 40 mg/dL (2.2 mmol/L), C-peptide level was 13.1 ng/mL (0.8-3.1 ng/mL), proinsulin level was 96.9 pmol/L (<18.8 pmol/L), and insulin level was 164 mU/L (<17 mU/L). An initial hypoglycemic agent screening, performed 24 hours after admission, yielded a negative result, leading to prolonged and recurrent hospitalizations for workup and localization of insulinoma. A hypoglycemic agent screening at a subsequent presentation, concordant with hypoglycemia, yielded a positive result for glipizide, which was at a level of 320 ng/mL (reporting limit, 40 ng/mL). An examination of the patient's home medications revealed a container, labeled as benztropine, containing glipizide tablets. After the diagnosis of glipizide-induced hypoglycemia, the patient had no further episodes of hypoglycemia.

The failure to detect glipizide using the initial hypoglycemia agent assay was likely because of a combination of a delay in the initial screening and low sensitivity of the assay for glipizide compared with that of other available assays. Here, we discuss important considerations for the interpretation of hypoglycemic agent screening in the diagnosis of hypoglycemia, including the timing of collection and reporting, pharmacokinetics of culprit agents, and sensitivity of the hypoglycemic agent panel used.

Screening tests for hypoglycemic agents are necessary for the evaluation of hypoglycemia because their biochemical evaluation may be indistinguishable from that of insulinoma.