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Diagnostic dilemmas in hypoglycemia: Illustrative cases

F John Service, MD, PhD
Adrian Vella, MD
Section Editor
Irl B Hirsch, MD
Deputy Editor
Jean E Mulder, MD


Insulinomas are rare tumors that may present a diagnostic dilemma for the clinician. The classic diagnostic test for an insulinoma has been the 72-hour fast. There are two reasons to perform a prolonged supervised fast. One is to confirm that hypoglycemia is the cause of the patient's symptoms and that reversing it relieves the symptoms (Whipple's triad). The second is to assess the role of insulin in the genesis of the hypoglycemia.

However, the need for a 72-hour fast is obviated when a patient has a spontaneous episode of symptomatic hypoglycemia that is fortuitously observed and confirmed with laboratory testing. The 72-hour fast is also unnecessary in the rare patient with insulinoma who has exclusively postprandial symptoms; in such cases, hypoglycemia is evaluated during a mixed-meal test. The presence of inappropriately high serum insulin, C-peptide, and proinsulin concentrations at the time of symptomatic and confirmed hypoglycemia in a patient who has a negative test for insulin secretagogues (sulfonylureas or meglitinides) establishes the diagnosis of insulinoma.

We consider the following values (measured in highly sensitive assays) as diagnostic of an insulinoma if the patient's serum glucose concentration is ≤45 mg/dL (2.5 mmol/L) in the presence of symptoms (table 1). (See "Hypoglycemia in adults without diabetes mellitus: Diagnostic approach".)

Serum insulin – ≥3 microU/mL (immunochemiluminometric assay [ICMA])

Serum C-peptide – ≥200 pmol/L

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Literature review current through: Nov 2017. | This topic last updated: Jan 03, 2017.
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