Diagnostic dilemmas in hypoglycemia: Illustrative cases
- F John Service, MD, PhD
F John Service, MD, PhD
- Emeritus Professor of Medicine
- Mayo Clinic College of Medicine
- Adrian Vella, MD
Adrian Vella, MD
- Professor of Medicine
- Mayo Clinic
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/LTo continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- O'Brien T, O'Brien PC, Service FJ. Insulin surrogates in insulinoma. J Clin Endocrinol Metab 1993; 77:448.
- Vinik AI, Renar IP. Insulin-producing tumors. Adv Endocrinol Metab 1993; 4:1.
- Rasbach DA, van Heerden JA, Telander RL, et al. Surgical management of hyperinsulinism in the multiple endocrine neoplasia, type 1 syndrome. Arch Surg 1985; 120:584.
- Levy MJ, Thompson GB, Topazian MD, et al. US-guided ethanol ablation of insulinomas: a new treatment option. Gastrointest Endosc 2012; 75:200.
- Merimee TJ, Fineberg SE. Homeostasis during fasting. II. Hormone substrate differences between men and women. J Clin Endocrinol Metab 1973; 37:698.
- Service FJ. Hypoglycemic disorders. N Engl J Med 1995; 332:1144.
- Lebowitz MR, Blumenthal SA. The molar ratio of insulin to C-peptide. An aid to the diagnosis of hypoglycemia due to surreptitious (or inadvertent) insulin administration. Arch Intern Med 1993; 153:650.
- Service FJ, O'Brien PC, McMahon MM, Kao PC. C-peptide during the prolonged fast in insulinoma. J Clin Endocrinol Metab 1993; 76:655.
- Doppman JL, Miller DL, Chang R, et al. Insulinomas: localization with selective intraarterial injection of calcium. Radiology 1991; 178:237.
- Stark DD, Moss AA, Goldberg HI, et al. Computed tomography and nuclear magnetic resonance imaging of pancreatic islet cell tumors. Surgery 1983; 94:1024.
- Fedorak IJ, Ko TC, Gordon D, et al. Localization of islet cell tumors of the pancreas: a review of current techniques. Surgery 1993; 113:242.
- Galiber AK, Reading CC, Charboneau JW, et al. Localization of pancreatic insulinoma: comparison of pre- and intraoperative US with CT and angiography. Radiology 1988; 166:405.