Clinical Implications of Various Criteria for the Biochemical Diagnosis of Insulinoma

Abstract

BackgroundAmong the various diagnostic criteria for insulinoma, the ratio criteria have been controversial. However, the amended insulin-glucose ratio exhibited excellent diagnostic performance in a recent retrospective cohort study, although it has not yet been validated in other patient cohorts. We examined the diagnostic performance of the current criteria of the Endocrine Society, insulin-glucose ratio, C-peptide-glucose ratio, and amended ratios in terms of differentiating insulinomas.MethodsWe reviewed the medical records of patients who underwent evaluation for hypoglycemia from 2000 to 2013. Fourteen patients with histopathologically confirmed insulinoma and 18 patients without clinical evidence of insulinoma were included. The results of a prolonged fast test were analyzed according to the abovementioned criteria.ResultsFulfilling all three Endocrine Society criteria-plasma levels of glucose (<3.0 mmol/L), insulin (≥8 pmol/L), and C-peptide (≥0.2 nmol/L)-exhibited 100% sensitivity and 89% specificity. Fulfilling the glucose and C-peptide criteria showed 100% sensitivity and 83% specificity, while fulfilling the glucose and insulin criteria showed 100% sensitivity and 72% specificity. Among the ratio criteria, the insulin-glucose ratio [>24.0 (pmol/L)/(mmol/L)] gave the highest area under the receiver operating characteristic curve, with 93% sensitivity and 94% specificity.ConclusionFulfilling the glucose, insulin, and C-peptide criteria of the Endocrine Society guidelines exhibited the best diagnostic performance for insulinoma. Nonetheless, the insulin-glucose ratio may still have a role in the biochemical diagnosis of insulinoma.

Diagnosis of insulinoma using the ratios of serum concentrations of insulin and C-peptide to glucose during a 5-hour oral glucose tolerance test

“…Insulin-to-glucose than ordinary three-hour OGTT in revealing an episode of hypoglycemia for the diagnosis of insulinoma [7]. Furthermore, the detection of elevated C-peptide during an OGTT also yields increased diagnostic reliability for insulinoma [8,9]. More importantly, due to wide variations in individual fasting serum insulin, the ratio of serum insulin to blood glucose has been recommended by several studies as a more reliable parameter for the diagnosis of insulinoma [10][11][12][13].…”

Insulinoma in a 5‐Year‐Old Dexter Cow

“…Insulin concentrations crossed a high peak concentration (2180 pmol/L) from an initial level of 54 pmol/L and decreased to a level of 322 pmol/L at 30 minutes postinfusion and remained elevated over the baseline concentration 5 hours long postinfusion (Fig ). Determination of the glucose/insulin ratio, which is the standard approach for diagnosis of insulinoma in dogs and humans, was not considered an appropriate diagnostic tool in cattle as the physiological range of insulin secretion and concentration in Dexter cows is unknown. The results of IVGTT reflecting persisting hyperinsulinemia after plasma glucose levels had already returned to subnormal levels further supported suspicion of an insulin‐secreting tumor.…”

“…Recently, intraabdominal ultrasonography was added to the diagnostic spectrum in humans to increase the diagnostic sensitivity of insulinomas . Biochemical diagnosis of insulinoma in humans relies on unequivocally measurable insulin concentrations in the fasting state, the concurrent measurement of C‐peptide together with quantitation of ketone bodies . Furthermore, evaluation of the insulin–glucose ratio is an important diagnostic parameter with a sensitivity of 93% and specificity of 94% .…”

“…15 Biochemical diagnosis of insulinoma in humans relies on unequivocally measurable insulin concentrations in the fasting state, the concurrent measurement of C-peptide together with quantitation of ketone bodies. 7 Furthermore, evaluation of the insulin-glucose ratio is an important diagnostic parameter with a sensitivity of 93% and specificity of 94%. 7 In the present case, the two monoclonal spikes in the alpha 1-fraction, which were detected by serum electrophoresis, were probably due to pregnancy or increased levels of C-peptide.…”

“…7 Furthermore, evaluation of the insulin-glucose ratio is an important diagnostic parameter with a sensitivity of 93% and specificity of 94%. 7 In the present case, the two monoclonal spikes in the alpha 1-fraction, which were detected by serum electrophoresis, were probably due to pregnancy or increased levels of C-peptide. However, a validated C-peptide assay for use in cattle is not available yet.…”