Bonus online case: Insulinoma with Whipple's triad

A patient reported repeated episodes of symptomatic hypoglycemia.


The patient

A 58-year-old woman with morbid obesity, hypertension, fibroidectomy, hypothyroidism, and asthma was transferred for persistent symptomatic hypoglycemia. At the transferring medical facility, she had been evaluated for possible stroke due to presentation with diaphoresis, anomic aphasia, bilateral arm heaviness, and inability to move her limbs but was found to have a serum glucose level of 32 mg/dL (reference range, 70 to 99 mg/dL). Vital signs and physical examination were normal except for tachycardia and obesity.

In the previous three years, she reported having episodes of “blood sugar in the 20s” during which she “felt drunk.” She had noticed that the symptoms improved with eating. Originally these episodes occurred once a month, but over the past two to three months, following the initiation of a low-carbohydrate diet for weight loss, they had become more frequent and severe, occurring several times a week.

Endocrine studies were notable for an elevated thyroid-stimulating hormone level of 5.927 MIU/L (reference range, 0.550 to 4.780 MIU/L) but normal free T4 level of 1.37 ng/dL (reference range, 0.89 to 1.76 ng/dL), as well as a fasting serum insulin level above 300.0 MIU/L (reference range, 0 to 29.1 MIU/L), a proinsulin level of 602.5 pmol/L (reference range, <18.9 pmol/L), a C-peptide level of 13.8 ng/mL (reference range, 0.2 to 2.7 ng/mL), a glucagon level of 488 pg/mL (reference range, 8 to 57 pg/mL), and a hemoglobin A1c level below 5.0%. Levels of beta-hydroxybutyrate, insulin-like growth factor I and II, cortisol, calcium, intact parathyroid hormone (PTH), and PTH-related protein were all within normal limits.

Figure 1 Hematoxylin and eosin HandE stain demonstrating a well-differentiated neuroendocrine tumor at 2less-thanigreater-thanxless-thanslashigreater-than magnification Image courtesy of Zaibo Li MD PhD department of pathology The O
Figure 1. Hematoxylin and eosin (H&E) stain demonstrating a well-differentiated neuroendocrine tumor at 2x magnification. Image courtesy of Zaibo Li, MD, PhD, department of pathology, The Ohio State University Wexner Medical Center.
Figure 2 HandE stain of neuroendocrine tumor at 20less-thanigreater-thanxless-thanslashigreater-than magnification Image courtesy of Zaibo Li MD PhD department of pathology The Ohio State University Wexner Medical Center
Figure 2. H&E stain of neuroendocrine tumor at 20x magnification. Image courtesy of Zaibo Li, MD, PhD, department of pathology, The Ohio State University Wexner Medical Center.

Due to concern for insulinoma, she underwent endoscopic ultrasound with fine-needle aspiration. Results were consistent with a pancreatic neuroendocrine tumor. Levels of gastrin, serotonin, somatostatin, vasoactive intestinal polypeptide, and chromogranin A were all within normal limits. CT of the chest, abdomen, and pelvis did not suggest metastatic disease. She underwent a robotic distal pancreatectomy with splenectomy, and pathology confirmed a well-differentiated neuroendocrine tumor (Figure 1 and Figure 2). For the 17 days from admission until the distal pancreatectomy, the patient required nocturnal 10% dextrose infusion due to symptomatic hypoglycemia.

The diagnosis

The diagnosis was insulinoma. Insulinoma is a neuroendocrine tumor arising from insulin-secreting pancreatic beta-cells with an incidence of one to three new cases per million persons per year by the fifth decade of life. However, due to the small size of these tumors (< 2 cm), the incidence is probably underestimated. When the patient fulfills Whipple's triad—symptoms of hypoglycemia, plasma glucose concentration below 55 mg/dL in the nondiabetic individual or below 70 mg/dL in the diabetic individual, and prompt relief of symptoms after glucose administration—insulinoma should be considered.

Establishing close follow-up with endocrinology is critical because 5% to 10% of insulinomas are associated with multiple endocrine neoplasia type 1, and up to 49% of patients can develop new-onset diabetes mellitus after distal pancreatectomy.

Pearls

  • Insulinoma should be considered in a patient who fulfills Whipple's triad.
  • Following distal pancreatectomy, patients should be monitored for new-onset diabetes mellitus.

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