Importance of Insulin Immunoassays in the Diagnosis of Factitious Hypoglycemia

Abstract

We report two cases emphasizing the importance of insulin assays for evaluation of hypoglycemia in diabetic patients. Case 1 was a 96/12-year-old female patient with type 1 diabetes mellitus and case 2 was a 1010/12-year-old male patient with DIDMOAD. Both patients were on a basal-bolus insulin regimen. Both were admitted because of persistent hypoglycemia. Analyses of serum samples obtained at the time of hypoglycemia initially showed low insulin and C-peptide levels. Recurrent episodes of unexplained hypoglycemia necessitated measurement of insulin levels by using different insulin assays, which revealed hyperinsulinemic hypoglycemia with low C-peptide levels, findings which confirmed a diagnosis of factitious hypoglycemia. Surreptitious administration of insulin should not be excluded in diabetic patients with hypoglycemia without taking into account the rate of cross-reactivity of insulin analogues with the insulin assay used.

Factitious hypoglycemia in children and adolescents with diabetes

“…Average age was 13.5 ± 2.0 years (range: 9.5‐18.0) and average diabetes duration was almost 6 years. All but 1 report, which described a 10.8‐year‐old boy with mitochondrial diabetes (Case 36, Reference ), included youths with type 1 diabetes. Recurrent DKA was mentioned in 7 cases and overall poor glycemic control was documented (HbA1c 12.1 ± 4.0%).…”

“…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.…”

A p.(Glu809Lys) Mutation in the WFS1 Gene Associated with Wolfram-like Syndrome: A Case Report

“…The disease is also known as the DIDMOAD syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, deafness). Most of the individuals afflicted with this disease have the recessive mutation in the WFS gene 1 (WFS1, 4p16.3) (1,2) and rarely in the WFS gene 2 (WFS2) (3). A dominant mutation in the WFS1 gene was also described in connection with sensorineural hearing loss, deafness, and optic atrophy [Wolfram-like syndrome (WFSL)] (4).…”