Hypoglycemia as a paraneoplastic syndrome - current state of knowledge

Abstract

Objective: To provide a comprehensive overview of current knowledge on paraneoplastic hypoglycemia, with particular focus on non-islet cell tumour hypoglycemia, including its epidemiology, pathophysiology, tumour associations, clinical presentation, diagnostic approach and management.

Methods: A literature review was conducted using articles retrieved from PubMed, Google Scholar and SpringerLink. Publications from 2020-2026 were screened using keywords related to non-islet cell tumour hypoglycemia and paraneoplastic hypoglycemia. Systematic reviews, review articles, case series and case reports published in English with full-text availability were included.

Results: Non-islet cell tumour hypoglycemia most commonly arises from mesenchymal tumours, particularly solitary fibrous tumours, but has also been reported in a broad spectrum of other tumour types. Hypoglycemia results from tumour overproduction of insulin-like growth factor two, especially its high-molecular-weight form, which mimics insulin activity. Patients typically present with fasting hypoglycemia, adrenergic and neuroglycopenic symptoms. Diagnosis is supported by a markedly elevated insulin-like growth factor two to insulin-like growth factor one ratio. Surgical tumour resection is the primary treatment; in unresectable cases, glucocorticoids, recombinant growth hormone, radiotherapy, or other emerging therapies may be used.

Conclusions: Early recognition and understanding of the diverse tumours causing non-islet cell tumour hypoglycemia are crucial to prevent hypoglycemia-related complications and support effective management.