The role of proinsulin and insulin in the diagnosis of insulinoma: a critical evaluation of the Endocrine Society clinical practice guideline

J Clin Endocrinol Metab. 2013 Dec;98(12):4752-8. doi: 10.1210/jc.2013-2182. Epub 2013 Sep 30.

Abstract

Context: An end of fast insulin ≥ 3 μIU/mL and a proinsulin concentration ≥ 5 pmol/L have been suggested as useful cutoffs for the diagnosis of insulinoma.

Objective: The main objective was to evaluate the diagnostic performance of an end of fast insulin concentration ≥ 3 μIU/mL and an end of fast proinsulin concentration ≥ 5 pmol/L.

Design: The design was a case-control series.

Setting: The setting was a tertiary-care center.

Patients: Fifty-six subjects with a positive 48-hour supervised fast had an insulinoma between June 2000 and April 2011. During this same time period, a diagnosis of insulinoma was excluded in 29 subjects who underwent a supervised fast.

Intervention: 48-hour supervised fast.

Main outcome measure: The main outcome measures were serum insulin concentration and plasma proinsulin concentration.

Results: Ninety-one percent of the patients with an insulinoma had a measured insulin concentration ≥5 μIU/mL at the end of fast. The sensitivity increased to 98% if the threshold to define inadequate insulin suppression was lowered to ≥3 μIU/mL. The median (interquartile range) end of fast proinsulin was 100 (53-270) pmol/L for cases and 6.8 (4.2-12.0) pmol/L for controls. An end of fast proinsulin value of ≥ 5 pmol/L could not distinguish cases from controls (59% false positive rate). All patients with an insulinoma (sensitivity 100%) and none of the control subject (specificity 100%) had end of fast proinsulin concentration ≥ 27 pmol/L.

Conclusions: Using a current insulin assay 9% of insulinoma cases end the supervised fast with an insulin concentration below 5 μIU/mL. Inadequate insulin suppression defined using a threshold of ≥ 3 μIU/mL increases the sensitivity of the test. The value of the proinsulin test lies in its unique ability to distinguish cases from controls. A proinsulin concentration of ≥22 pmol/L best discriminates cases from controls. Reliance on an end of fast proinsulin cutoff value of 5 pmol/L does not augment sensitivity but greatly reduces specificity of the test.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Case-Control Studies
  • Fasting
  • Female
  • Humans
  • Insulin / blood*
  • Insulinoma / blood
  • Insulinoma / diagnosis*
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / blood
  • Pancreatic Neoplasms / diagnosis*
  • Practice Guidelines as Topic
  • Proinsulin / blood*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Societies, Scientific
  • Tertiary Care Centers

Substances

  • Insulin
  • Proinsulin