A nationwide survey of endogenous hyperinsulinemic hypoglycemia in Japan (2017–2018): congenital hyperinsulinism, insulinoma, noninsulinoma pancreatogenous hypoglycemia syndrome, and insulin autoimmune syndrome (Hirata's disease)

AIMS: We aimed to investigate the nationwide incidence, treatment details, and outcomes of patients with endogenous hyperinsulinemic hypoglycemia (EHH), including those with transient/persistent congenital hyperinsulinism (CHI), insulinoma, noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS), and insulin autoimmune syndrome (Hirata's disease) in Japan. MATERIALS AND METHODS: A nationwide, questionnaire-based survey was conducted to determine the number of patients with EHH who were treated for hypoglycemia or hypoglycemia-related complications in 2017-2018. The questionnaires were sent to all hospitals in Japan with >300 beds and with pediatric and/or adult clinics likely managing EHH patients. The secondary questionnaires were sent to obtain the patients' date of birth, sex, age at onset, treatment details, and posttreatment outcomes. RESULTS: A total of 447 patients with CHI (197, transient CHI; 225, persistent CHI; and 25, unknown histology), 205 with insulinoma (118, benign; 18, malignant; and 69, unknown subtype), 111 with NIPHS (33, post-gastric surgery HH; 57, postprandial HH; 10, nesidioblastosis; and 11 unknown subtype), and 22 with insulin autoimmune syndrome were identified. Novel findings included (1) marked improvement in the prognosis of persistent CHI over the past 10 years, (2) male dominance in the incidence of transient CHI, (3) NIPHS emerging as the second most common form of EHH in adults, (4) frequent association of diabetes mellitus with insulin autoimmune syndrome, and (5) frequent posttreatment residual hypoglycemia and impaired quality of life. CONCLUSIONS: The first nationwide, all age-group survey of EHH revealed the current status of each type of EHH disorder and the unmet needs of the patients.