Unraveling the Whipple Triad: Non–Islet Cell Tumor–Induced Hypoglycemia

Abstract

Abstract Tumor-induced hypoglycemia (TIH) is a rare paraneoplastic phenomenon resulting from several tumor types and mechanisms. Insulinomas are the most common cause of TIH. However, non–islet cell tumors can also trigger hypoglycemia by releasing insulin-like growth factor 2 (IGF-II) or its precursor. We present a case of a 56-year-old woman experiencing spontaneous hypoglycemia due to a pleural-based solitary fibrous tumor. Diagnostic evaluations revealed diminished C-peptide levels, increased IGF-II, and a 4-fold increase in the IGF-II: IGF-I ratio, indicative of non–islet cell tumor hypoglycemia. Localization imaging identified a left pleural mass, confirming the diagnosis. Preoperatively, the patient received intravenous dextrose and corticosteroids, but surgical resection was essential for the resolution of symptoms. The identified tumor, a benign solitary fibrous tumor, was successfully removed, leading to an immediate postoperative cessation of hypoglycemia. Six years post resection, the patient remains symptom free. Managing TIH necessitates an early diagnosis aiming for complete tumor resection, with alternative approaches considered when complete resection is not possible. This case highlights the importance of a systematic diagnostic and management approach for TIH, emphasizing the need to identify the underlying cause, particularly in people without diabetes.