A 30-year-old Hispanic male presents to the office with complaints of palpitations, tremor, nervousness and headache. His past history is insignificant. His mother has type 2 diabetes, which is well-controlled with medications. His temperature is 37.0° C (98.6° F), pulse is 100/min, blood pressure is 150/80 mm Hg, and respirations are 16/min. He appears anxious, sweaty and shaky. His neurological examination is non-focal, and examination of other systems is unremarkable. His fingerstick blood glucose level is 38 mg/dL. Intravenous administration of a bolus of 50% dextrose leads to the improvement of his symptoms. He is then subjected to supervised prolonged fasting. After an overnight fast, laboratory studies reveal:
Blood glucose 40 mg/dL Serum insulin 15 microU/L (normal value is < 6 microU/L with hypoglycemia) Serum pro-insulin 9 microU/L (normal value is < 20% of total immunoreactive insulin) C-peptide level 0.8 nmol/L (normal value is less than 0.2 nmol/L) Sulfonylurea Negative IGF-II Negative
Based on the above information, what is the most likely cause of this patient's hypoglycemia?
In normal individuals, a blood glucose level below 60 mg/dL results in near-complete suppression of insulin secretion. The patient in this vignette thus presents with hypoglycemia and inappropriately elevated serum insulin levels.
There are two important causes of hypoglycemia in non-diabetic patients with elevated insulin levels:
Elevated C-peptide levels and proinsulin levels greater than 5 pmol/L are seen in patients with beta cell tumors; therefore, this is the most likely diagnosis.
(Choice B) Non-beta cell tumors, typically large mesenchymal tumors, can lead to hypoglycemia independent of insulin. Such tumors produce insulin-like growth factor II (IGF II), which has an insulinomimetic action after binding to insulin receptors. In patients with suspected non-beta cell tumors, the serum IGF II level can be measured. Patients with this condition characteristically have suppressed insulin and c-peptide levels.
(Choice C) Sulfonylurea causes an increased output of endogenous insulin from the beta cells. Patients with sulfonylurea-induced hypoglycemia are sometimes difficult to differentiate from those with insulinoma because increased insulin and c-peptide levels are seen in both groups. Nonetheless, the proinsulin level is sometimes lower than 20% of the total insulin immunoreactivity. The diagnosis is confirmed by measuring the plasma sulfonylurea level.
(Choice D) Exogenous insulin-induced hypoglycemia is associated with very high serum insulin levels combined with low c-peptide levels. The low c-peptide levels result from the suppression of endogenous insulin production.
(Choice E) Glucagonoma produces a characteristic skin rash (necrotic migratory erythema) with elevated blood glucose levels (not hypoglycemia).
Educational Objective:
Hypoglycemia is associated with multiple differential diagnoses. Helpful tests used in the evaluation of hypoglycemic patients are measurements of c-peptide, proinsulin and sulfonylurea levels. Hypoglycemia secondary to insulinoma is associated with elevated insulin, c-peptide and proinsulin levels.