Commercial insulin immunoassays fail to detect commonly prescribed insulin analogues

Factitious hypoglycemia in children and adolescents with diabetes

“…The diagnosis was further delayed during the subsequent work‐up because of the use of an insulin assay that did not detect exogenous insulin. Similar cases have previously been reported . Many inventive strategies have been described for surreptitious insulin administration.…”

“…She had first learned about self‐induced hypoglycemia when attending a summer camp for children with type 1 diabetes (similar to reports in References and ) at the age of 8 years. The diagnosis was delayed because of misleading laboratory results (no or low plasma insulin concentrations due to the use of a highly specific insulin assay which did not cross‐react with insulin analogs, also described in References and due to only reviewing the insulin pump's memory of total daily insulin doses, and not downloading the insulin pump's “priming history” (see References and ). Our interventions consisted primarily in consolidation of care and individual psychotherapy.…”

“…The typical laboratory paradigm to differentiate exogenous insulin induced factitious hypoglycemia (low C‐peptide, high insulin) from an insulinoma (high C‐peptide, high insulin) or other causes (low C‐peptide, low insulin) may not be easily applicable. Today's highly specific insulin assays do not (or to a lower degree) detect recombinant insulin analogs . An additional diagnostic challenge is the preconceived notion that children do not intentionally harm themselves.…”

“…It was realized that this assay, while extremely sensitive to endogenous insulin, had highly variable cross‐reactivity with several insulin analogs. In particular, this assay had no cross‐reactivity with insulin glulisine . Thus, stored plasma samples were sent out to be analyzed with an Abbott Architect immunoassay.…”

Effective Use of Mass Spectrometry in the Clinical Laboratory

“…MS offers a cost-effective alternative to measure traditional RIA-measured analytes like free testosterone, insulin, prolactin, and 1,25-dihydroxyvitamin D. Alternatively, the cost of some traditional, lower-volume immunoassays like C-peptide or ␤-hydroxybutyrate, which may exceed $20/test on commercial platforms, can be done for substantially less by MS while providing superior results. Recently, the cross-reactivity of 10 different immunoassays with 15 exogenous insulins was examined and the authors concluded that, due to the poor crossreactivity of the immunoassays, MS should be used to diagnose hypoglycemia secondary to exogenous insulin (36 ). Although any single assay may not be enough to justify the costs of a mass spectrometer and all the required laboratory renovations, development, validation, training, and labor, combinations of multiple in-house and/or send-out tests can be used to successfully justify the acquisition of this technology.…”