Version July 2025
BHB: beta-hydroxybutyrate; IGF: insulin-like growth factor.
* Additional testing should be pursued to demonstrate increased pro-IGF-2 and free (unbound) IGF-2 levels with an elevated IGF-2/IGF-1 ratio. If nonislet cell tumor hypoglycemia is excluded, the most likely causes of hypoglycemia are administration of an insulin analog not detected by the laboratory assay or insulinoma/proinsulinoma. Detection of insulin analogs may require specialized testing. An elevated proinsulin level suggests insulinoma/proinsulinoma.
¶ Exclusion of insulin- or IGF-mediated causes of hypoglycemia is further corroborated by an increase in blood glucose concentration ≤25 mg/dL (1.4 mmol/L) after glucagon administration.
Δ Fasting glucose values between 40 to 60 mg/dL (2.2 to 3.3 mmol/L) can reflect normal physiology in healthy, young adults. However, a glucose value <40 mg/dL (2.2 mmol/L) is very unlikely to reflect normal physiology and requires additional evaluation.
◊ If antibodies are negative, the most likely etiology is insulinoma and should be evaluated further with tumor localizing studies. Tumor localization is reviewed in detail in other UpToDate content.
§ In patients who have not undergone bariatric surgery, insulinoma is most likely and should be evaluated further with tumor localizing studies. Tumor localization is reviewed in detail in other UpToDate content.