Non-Islet Cell Tumor Hypoglycemia in Metastatic High-Grade Undifferentiated Mesenchymal Sarcoma: Complete Resolution after Palliative Above-Knee Amputation

Background: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome that is mainly caused by the excessive production of incompletely processed insulin-like growth factor-2 (big IGF-2) by non-pancreatic tumors; it is most frequently linked to large mesenchymal neoplasms, even though it is very rare in cases of metastatic high-grade undifferentiated mesenchymal sarcoma. Diagnosis is especially difficult in areas with limited resources because there are no specialized IGF-2 assays available.
Case Presentation: A 66-year-old woman was diagnosed with high-grade undifferentiated mesenchymal sarcoma of the distal left femur, with pulmonary metastases. She declined the initially offered palliative above-knee amputation and was treated with anthracycline-based chemotherapy and pazopanib. Repeat radiologic imaging of the primary site after 6 courses of chemotherapy showed a partial response. However, she developed recurrent episodes of fasting hypoglycemia, with associated symptoms such as sweating, confusion, and weakness, and a single episode of loss of consciousness. Biochemical evaluation confirmed hypoglycemia and identified no other potential causes, supporting a probable diagnosis of NICTH. There was associated intractable pain that was not controlled with analgesics. An above-knee amputation was performed as a palliative procedure. The hypoglycemia resolved completely within 48 hours of the operation.
Conclusion: NICTH should be considered in patients with large mesenchymal sarcomas accompanied by recurrent fasting hypoglycemia, and it is proven that palliative tumor resection can completely eradicate paraneoplastic hypoglycemia even in the presence of residual metastatic disease; this therefore highlights the importance of multidisciplinary care and of early surgical intervention, especially in resource-limited settings.

NICTH (non-islet cell tumor hypoglycemia); High-Grade Undifferentiated Mesenchymal Sarcoma

1. Jannatalipour A, Panahi N, Pejman Sani M, Ghaemi O, Kheirandish M, Alipour N, Zarinkolah A, Jawhari M, Rasuli B, Mohajeri-Tehrani MR, Aghaei Meybodi HR, Soltani A. Non-islet cell tumor hypoglycemia (NICTH) associated with sarcoma: case report. BMC Endocr Disord. 2025;25(1):59. doi:10.1186/s12902-025-01885-5. [Google Scholar] [Crossref]

2. Vu A, Chik C, Kwong S. IGF-2-mediated hypoglycemia: a case series and review of the medical therapies for refractory hypoglycemia. Endocrinol Diabetes Metab Case Rep. 2024;2024(1):23-0089. doi:10.1530/EDM-23-0089. [Google Scholar] [Crossref]

3. Yu B, Douli R, Suarez JA, Gutierrez VP, Aldiabat M, Khan M. Non-islet cell tumor hypoglycemia as an initial presentation of hepatocellular carcinoma coupled with end-stage liver cirrhosis: a case report and review of literature. World J Hepatol. 2020;12(8):519-24. doi:10.4254/wjh.v12.i8.519. [Google Scholar] [Crossref]

4. Bodnar TW, Acevedo MJ, Pietropaolo M. Management of non-islet-cell tumor hypoglycemia: a clinical review. J Clin Endocrinol Metab. 2014;99(3):713-22. doi:10.1210/jc.2013-3382. [Google Scholar] [Crossref]

5. Legare TB, Hamilton O, Dhannoon S, Ali S. Non-islet cell tumor hypoglycemia: a rare cause of hypoglycemia in pulmonary sarcomatoid cancer. Cureus. 2017;9(12):e1972. doi:10.7759/cureus.1972. [Google Scholar] [Crossref]

6. Matthews E, Schmitt B, Passeri M, Mizenko C, Orjuela K, Piquet A. AMPA receptor encephalitis in a patient with metastatic breast cancer receiving palbociclib: a case report. Neurol Neuroimmunol Neuroinflamm. 2022;9:e200012. doi:10.1212/NXI.0000000000200012. [Google Scholar] [Crossref]

7. Slack M, Sovich A, Sachs C, Martinez D, Yu R. A case of nonislet cell tumor hypoglycemia due to metastatic salivary myoepithelial carcinoma. AACE Clin Case Rep. 2024;10:184-7. [Google Scholar] [Crossref]

8. van den Berg SAA, Krol CG. Pro-IGF2-induced hypoglycemia associated with hepatocellular carcinoma. Endocrinol Diabetes Metab Case Rep. 2017;2017:17-0004. doi:10.1530/EDM-17-0004. [Google Scholar] [Crossref]

9. Anikhindi A, Aman C, Aneesha M. Non-islet cell tumor hypoglycemia from an occult Müllerian tumor: a rare paraneoplastic presentation. J Clin Images Med Case Rep. 2026;7:1-5. [Google Scholar] [Crossref]

10. Wilson JM, Ginsberg J, Cutts K, Urban S. A Case of Non-Islet Cell Tumor Hypoglycemia (NICTH) Associated with Gastrointestinal Stromal Tumor (GIST). Am J Case Rep. 2017 Sep 13;18:984-988. doi: 10.12659/ajcr.904753. PMID: 28900071; PMCID: PMC5608149. [Google Scholar] [Crossref]

11. Hu X, Zhou L, Tian Y, Li X and Lu T. Primary malignant peripheral nerve sheath tumor of the liver: a case report and literature review. Front. Oncol. 16:1795231. doi: 10.3389/fonc.2026.1795231 [Google Scholar] [Crossref]

12. Douillard, Claire & Jannin, Arnaud & Vantyghem, Marie-Christine. Rare Causes of Hypoglycemia In Adults. Annales d'Endocrinologie. 81. 10.1016/j.ando.2020.04.003. [Google Scholar] [Crossref]

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