Lessons From Case Reports
Alia Munir
JCEM Case Reports, Volume 3, Issue 12, December 2025, luaf270
https://doi.org/10.1210/jcemcr/luaf270
Hypoglycemia in individuals without exogenous insulin use is uncommon and heterogeneous, with an estimated frequency of 36 per 10,000 hospital admissions. Serious sequalae may occur, particularly with missed or delayed diagnosis. Although rare, here we reflect on 3 recently published case reports on the clinical theme of nondiabetic hypoglycemia and review the unique aspects of the presentation, diagnosis, and treatment. The mechanisms contributing to hypoglycemia in the 3 case reports differ, ranging from a tiny β-cell neuroendocrine tumor secreting insulin autonomously, dysautonomia in Ehlers-Danlos syndrome (EDS) with gastrointestinal (GI) dysmotility and amplify postprandial insulin excursions, to a novel heterozygous mutation in the glucokinase (GCK) gene, lowering the glucose threshold for insulin secretion. Together, these reports remind us to first use a mechanism-based approach to diagnosis. Returning to first principles of a detailed medical history followed by a clinical review of the patient to ensure fulfillment of Whipple triad is key. Then it is important to classify the hypoglycemia in relation to timing of food intake and tailor subsequent investigations in line with Endocrine Society and European Neuroendocrine Tumor Society (ENETS) guidance. The aim should be timely diagnosis with avoidance of overmedicalization and investigation with early multidisciplinary collaboration.
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