Clinical features and causes of endogenous hyperinsulinemic hypoglycemia in Korea

Abstract

Background: Endogenous hyperinsulinemic hypoglycemia (EHH) is characterized by an inappropriately high plasma insulin level, despite a low plasma glucose level. Most of the EHH cases are caused by insulinoma, whereas nesidioblastosis and insulin autoimmune syndrome (IAS) are relatively rare.

Methods: To evaluate the relative frequencies of various causes of EHH in Korea, we retrospectively analyzed 84 patients who were diagnosed with EHH from 1998 to 2012 in a university hospital.

Results: Among the 84 EHH patients, 74 patients (88%), five (6%), and five (6%) were diagnosed with insulinoma, nesidioblastosis or IAS, respectively. The most common clinical manifestation of EHH was neuroglycopenic symptoms. Symptom duration before diagnosis was 14.5 months (range, 1 to 120 months) for insulinoma, 1.0 months (range, 6 days to 7 months) for nesidioblastosis, and 2.0 months (range, 1 to 12 months) for IAS. One patient, who was diagnosed with nesidioblastosis in 2006, underwent distal pancreatectomy but was later determined to be positive for insulin autoantibodies. Except for one patient who was diagnosed in 2007, the remaining three patients with nesidioblastosis demonstrated severe hyperinsulinemia (157 to 2,719 µIU/mL), which suggests that these patients might have had IAS, rather than nesidioblastosis.

Conclusion: The results of this study suggest that the prevalence of IAS may be higher in Korea than previously thought. Therefore, measurement of insulin autoantibody levels is warranted for EHH patients, especially in patients with very high plasma insulin levels.

Keywords: Autoimmune diseases; Hyperinsulinism; Hypoglycemia; Insulin antibodies; Insulinoma; Nesidioblastosis.

Fig. 1. Flow diagram of the localization strategies used to identify endogenous hyperinsulinemic hypoglycemia (EHH) patients. OGTT, oral glucose tolerance test; CT, computed tomography; MRI, magnetic resonance imaging; EUS, endoscopic ultrasound; THPVS, trans-hepatic portal vein sampling; SACS, selective arterial calcium stimulation.

Fig. 2. Plasma insulin levels in patients diagnosed with insulinoma, nesidioblastosis, and insulin autoimmune syndrome (IAS). The case indicted by the arrow demonstrated positive results on the insulin autoantibody test (3,000 µIU/mL, case no. 9 in Table 2). The other case indicated by the head of arrow demonstrated negative results on the insulin autoantibody test (5 µIU/mL, case no. 10 in Table 2).