A 44-year-old nurse presents to the emergency department with confusion. This has happened several times this past month with increasing frequency. Each time her symptoms improved with eating. She is otherwise healthy. She lives with her mother who has diabetes whose medications include metformin, insulin, lisinopril, amlodipine, and glyburide. Her temperature is 98.0°F (36.7°C), blood pressure is 132/81 mmHg, pulse is 85/min, respirations are 16/min, and oxygen saturation is 98% on room air. Physical exam reveals a confused woman. She is moving all her extremities but follows commands poorly. Laboratory studies are ordered as seen below.

Hemoglobin: 14 g/dL
Hematocrit: 41%
Leukocyte count: 7,500/mm^3 with normal differential
Platelet count: 199,000/mm^3

Serum:
Na+: 140 mEq/L
Cl-: 102 mEq/L
K+: 4.0 mEq/L
HCO3-: 23 mEq/L
BUN: 30 mg/dL
Glucose: 29 mg/dL
Creatinine: 1.4 mg/dL
Ca2+: 10.2 mg/dL
Sulfonylurea level: undetectable
C-peptide level: 55 ng/mL (normal < 5 ng/mL)

Which of the following is the most likely etiology of this patient’s symptoms?
Insulin overdose
Beta cell tumor
Sulfonylurea overdose
Beta cell destruction
Beta cell tumor
This patient is presenting with confusion, profound hypoglycemia, an elevated C-peptide level, and a negative sulfonylurea level, which are concerning for an insulinoma. An insulinoma is a beta cell tumor that secretes insulin.

An insulinoma is a beta cell tumor of the pancreas. The beta cells normally secrete insulin in response to increased circulating fuel substrate (such as glucose or fat). In the setting of an insulinoma, insulin is pathologically and continuously secreted. This leads to profound, recurrent episodes of hypoglycemia. When a patient presents with hypoglycemia of unclear etiology; a blood glucose level, C-peptide level, and sulfonylurea level should be ordered. An infectious workup may be indicated as sepsis can also cause hypoglycemia. In an insulinoma, patients will be hypoglycemic, have an elevated C-peptide level (as this is a marker of endogenous insulin release), and a negative sulfonylurea level (important to rule out as a sulfonylurea overdose can also cause hypoglycemia in the setting of an elevated C-peptide level). Further workup will involve imaging of the abdomen such as a CT scan or MRI (more accurate) to delineate this insulin-secreting mass.

Mathur et al. discuss insulinoma. They note that it is a rare endocrine tumor, and note its association with multiple endocrine neoplasia type 1. They recommend workup for an insulinoma should occur in patients with recurrent episodes of hypoglycemia without a clear cause.

Incorrect Answers:
Answer A: Alpha cell tumor describes a glucagonoma, which pathologically secretes glucagon leading to profound hyperglycemia, a classic rash termed necrolytic migratory erythema (presents with painful, erythematous papules and plaques), and gastrointestinal symptoms including anorexia, abdominal pain, and diarrhea.

Answer B: Beta cell destruction describes the pathophysiology of type I diabetes mellitus, which presents in pediatric patients (most commonly) with hyperglycemia, weight loss, polydipsia, and polyuria. Treatment involves the administration of insulin. An initial presentation of type I diabetes may be diabetic ketoacidosis which presents with dehydration, abdominal pain, nausea, vomiting, Kussmaul respirations, and an anion gap acidosis.

Answer D: Insulin overdose would present with hypoglycemia, somnolence, confusion, and tremulousness. Note that exogenous insulin administration would not elevate the C-peptide level, which is a marker of endogenous insulin production.

Answer E: Sulfonylurea overdose would cause hypoglycemia that is often persistent given the long half-life of sulfonylureas. It would also elevate the C-peptide level as these medications increase the endogenous release of insulin. However, the sulfonylurea level was negative in this patient. While iatrogenic use of medications is plausible in this patient who has knowledge of medications (as she is a nurse), her repeat episodes and her workup suggesting against an iatrogenic etiology makes an insulinoma a more likely diagnosis.

Bullet Summary:
Insulinomas are beta cell tumors of the pancreas and lead to severe hypoglycemia and an elevated insulin and C-peptide level.