Introduction: The diagnosis of insulinoma has well established criteria that depends on intact renal function. We present a case of insulinoma in a patient with advanced CKD.
Background: Review of the literature reveals only three prior reports of confirmed insulinoma in patients with advanced CKD since the discovery of insulin in 1921. Due to decreased renal gluconeogenesis, hypoglycemia is not uncommon in the setting of CKD, so the index for suspicion for insulinoma is low. The standard for insulinoma diagnosis is based on inappropriately elevated insulin and C-peptide levels in the presence of significant hypoglycemia. Advanced CKD alone can cause elevated insulin and C-peptide levels due to impairment of insulin clearance and degradation. Thus the positive predictive value of a 72 hour fast for evaluation of glucose, insulin, pro-insulin, and C-peptide is low in patients with advanced CKD. It has been suggested that a low betahydroxybutyrate (BHB) level during a 72 hour fast may be a more reliable diagnostic test due to the antiketogenic effects of insulin.
Clinical Case: A 78 year old female with hypertension, CKD stage IV and type 2 diabetes (T2DM), with prior treatment with metformin that was stopped 3 years previously, was transferred to our facility for recurrent hypoglycemia. For 1-2 years prior to presentation, the patient (pt) had been having neuroglycopenic and autonomic symptoms that occurred while fasting in the early morning hours. Symptoms were relieved by drinking juice. During hospitalization, the pt developed hypoglycemia fifteen hours into her fast with serum glucose of 38 mg/dL, insulin level 9 uIU (reference <6 uIU/mL), proinsulin 27.2 pmol/L (reference <5pmol/L), C-peptide 2.13 ng/mL (reference <0.2 ng/mL), and low BHB <1.8 mg/dL (reference >2.7 mg/dL). Estimated GFR was 22 ml/min/1.73 m2, with serum creatinine 2.59 mg/dL. Insulin antibody level was 0.4 U/mL (reference < 0.4 U/mL ). Drug screen for hypoglycemic agents was negative. Although a transabdominal ultrasound and a CT scan of the abdomen and pelvis showed no pathology, an endoscopic ultrasound revealed a single hypoechoic pancreatic body lesion measuring 1.3 x 1.2 cm. Ultrasound guided fine needle aspiration revealed a uniform population of round or oval neoplastic cells concerning for neuroendocrine tumor (NET). The pt underwent subtotal pancreatectomy, splenectomy and cholecystectomy. Pathology showed a well differentiated, grade 1 NET. Post-operatively, the hypoglycemia episodes resolved although the pt developed hyperglycemia consistent with her T2DM history.
Conclusion: In the setting of advanced CKD, the presumptive biochemical diagnosis of insulinoma cannot be made on biochemical criteria alone, but requires positive confirmation by imaging and pathology, and is a challenging diagnosis to make accurately.
Shamleffer, A. Shaik, S. Harnoor, A. Cook, F. Jerkins Drake, J. (2018, March 19). The Challenging Diagnosis Of Insulinoma In Chronic Kidney Disease (ckd). Poster Presented at: The Endocrine Society ENDO 2018 Annual Meeting, Chicago, IL.