The Ups and Downs of Diagnosing Insulinoma

Introduction:
Insulinomas are rare neuroendocrine tumors of the pancreas. The diagnosis of an insulinoma may be delayed in the geriatric population, as older individuals often have comorbid conditions making evaluation more difficult. The case described here involves an exceptionally rare presentation of insulinoma in a 78-year-old male with underlying type 2 diabetes mellitus and heart failure.

Case Description:
A 78-year-old man with a past medical history of type 2 diabetes, heart failure, and chronic kidney disease presented to the hospital with bilateral lower extremity edema and shortness of breath. He had been hospitalized four times during the previous six months for acute heart failure exacerbations accompanied by recurrent episodes of hypoglycemia. Of note, his diabetes was well-controlled with glimepiride and dapagliflozin only. 

The patient reported symptomatic hypoglycemia, primarily during fasting episodes, with nadir serum glucose values between 40 and 50 mg/dL. During hospitalizations, total insulin (range 22-68 uU/mL), and C peptide (range 6.9-16.4 ng/mL) concentrations were inappropriately elevated when glucose was low, indicative of endogenous hyperinsulinemia. However, this hypoglycemia was thought to be secondary to recent sulfonylurea use in the setting of poor diet and acute renal insufficiency related to heart failure. Both glimepiride and dapagliflozin were held, though he inadvertently continued to take glimepiride until his fourth hospitalization.

During his fourth admission, the patient continued to have symptomatic hypoglycemia. As his sulfonylurea screen was negative, he underwent an Octreoscan that revealed radiotracer uptake in the distal pancreas. An endoscopic ultrasound with biopsy revealed a well-differentiated neuroendocrine tumor of the pancreas. His heart failure made agents such as diazoxide, verapamil, and phenytoin undesirable, and he was discharged on subcutaneous octreotide three times daily with a plan to follow up in the surgery clinic.

Discussion:
The presentation of insulinomas in the geriatric population can be variable and nonspecific, increasing the risk of misdiagnosis or delay of diagnosis. Missing the diagnosis can lead to increased morbidity and mortality via cognitive impairment and falls.  Our patient experienced a delay in diagnosis of insulinoma of over one year despite satisfying the criteria of Whipple’s triad during his first admission. The patient had been asked to stop all anti-diabetic medications during his third admission.  However, he misunderstood and continued glimepiride. Further, his acute renal insufficiency, heart failure, and decreased appetite provided alternative causes for his hypoglycemia.

Insulinomas are extremely rare pancreatic neuroendocrine tumors that typically present in patients between 40 and 60 years of age. However, there have been reports of these rare tumors in older individuals, who often have comorbid conditions making their diagnosis more difficult. This case report highlights the importance of including insulinoma as a cause of persistent endogenous hypoglycemia among the geriatric population.