Endocrine Abstracts

Background: Non-Diabetic Hypoglycemia is a rare entity in Endocrinology. After the confirmation of hypoglycemia with Whipple’s triad and excluding drug induced hypoglycemia, identification of underlying etiology using appropriate and targeted investigations is fundamental to institute specific management. It is challenging in resource poor settings due to unavailability and high cost of some investigations such as insulin autoantibodies and insulin-like growth factr-2 (IGF-2) level.

Methods: We retrospectively analyzed 11 patients who were diagnosed with non-diabetic hypoglycemia in 2023, in a tertiary care center in Sri Lanka

Results: Among the 11 patients, six patients, three and one were diagnosed with insulinoma, Insulin autoimmune syndrome (IAS) and nesidioblastosis respectively. Another one patient with neurofibromatosis type 1(NF-1) was diagnosed with non-islet cell tumor hypoglycemia (NICTH) due to metastatic gastrointestinal stromal tumor (GIST). Among patients with insulinoma, 2 had multifocal insulinoma in the background of MEN-1 syndrome and NF-1 respectively. Among cases of IAS, two were idiopathic and the other one was carbimazole induced. The patient with nesidioblastosis didn’t have a history of gastric surgeries. Most patients had recurrent level-3 hypoglycemia. Timing of the symptoms, whether fasting or postprandial was not reliably helpful in differentiating between the etiologies because one patient with insulinoma had predominantly post-prandial hypoglycemia and two patients with IAS had almost fasting symptoms. All cases of insulinoma and nesidioblastosis had insulin/c-peptide ratio of less than one with insulin recovery after PEG precipitation of more than 70%, while all three patients with IAS had very high insulin levels with the ratio of much more than one and insulin recovery after PEG precipitation of less than 10%. The diagnosis of IAS was confirmed by the presence of insulin autoantibodies in all cases. The case of NICTH had hypo-insulinemic hypoglycemia with suppressed beta-hydroxy butyrate level, low IGF-1 and positive response to glucagon challenge test. IGF-2 level could not be performed.

Conclusion: This series highlights the challenges in identifying the cause of non-diabetic hypoglycemia especially in resource poor settings. The timing of hypoglycemia is not a good indicator to differentiate the etiologies. In the resource-limited settings where insulin autoantibodies cannot be done freely, insulin/c-peptide ratio with insulin recovery after PEG precipitation might be a good alternative to diagnose IAS. The diagnosis of NICTH can be made in a patient with malignancy having hypo-insulinemic hypoglycemia with suppressed ketogenesis, low IGF-1 and positive glucagon challenge test as IGF-2 assay is very expensive and not available in many settings.