Clinical Presentation and Outcomes of Insulinomas in Pediatric Patients

Introduction. Insulinomas are the leading cause of hyperinsulinemic hypoglycemia in adults, but they can also present during childhood, and, when they do, diagnosis and localization of the lesion can be difficult. Moreover, differentiating between congenital hyperinsulinism (HI) and pediatric insulinomas is challenging because both diseases have similar presentation. Our objective was to review the clinical presentation, diagnostic characteristics, and success of methods for localization, treatment, and outcomes in pediatric patients with insulinomas. Methods. Retrospective study of patients with confirmed insulinoma treated at a single academic pediatric hospital between 2006 and 2024. Descriptive statistics and logistic regression models were used to quantify the data and discriminate between groups, respectively. The optimal operating point (OOP) for diagnostic laboratory data was used to maximize discrimination between insulinomas and congenital hyperinsulinism (HI), with prediction accuracy determined by the sensitivity and specificity at the OOP. Results. We reviewed the records of 23 patients with insulinoma with a median age at presentation of 13 years. A positive family history of multiple endocrine neoplasia type 1 (MEN1) was recorded in 22%. The most common presenting symptom was altered mental status. Median plasma insulin and beta-hydroxybutyrate (BOHB) concentrations during hypoglycemia were 8.8 uIU/mL (61.1 pmol/L) and 0.3 mmol/L, respectively. Most patients had four imaging studies completed to localize their insulinoma. Twenty of the 23 patients reviewed had a single lesion successfully resected and were cured. Of these 20 patients, 12 had 18F-Fluoro-dihydroxyphenylalanine (18F-DOPA) positron emission tomography/computed tomography (PET/CT) completed, of which nine were positive (75%). Three patients had initial lesions localized and successfully resected but continued to have hypoglycemia requiring medical management. Median duration from presentation to surgery was 9 weeks. When comparing the critical samples of patients with insulinomas and HI, the combination of BOHB and insulin-like growth factor binding protein 1 (IGFBP-1) at the time of hypoglycemia yielded a sensitivity and specificity of 0.89 and 0.84, respectively, for insulinoma versus HI when using a multivariate function on our cohorts. Conclusion. In this series, successful treatment of insulinomas took, on average, 9 weeks from diagnosis. Multiple imaging modalities were employed for preoperative lesion localization, with 18F-DOPA PET/CT and MRI being the most successful. Improved imaging modalities are needed to localize insulinomas in pediatric patients and reduce the time between diagnosis and resection. We propose an algorithm to differentiate between pediatric insulinomas and congenital hyperinsulinism using laboratory data to quicken diagnosis and lessen time to treatment.