Managing Non-islet Cell Tumor Hypoglycemia in Hepatocellular Carcinoma With Radiation Therapy

Non-islet cell tumor hypoglycemia (NICTH) is a paraneoplastic syndrome associated with non-mesenchymal-derived and epithelial tumors. A 37-year-old male with stage IVB hepatocellular carcinoma (HCC) and pulmonary metastases presented with recurrent hypoglycemia despite glucose supplementation. Laboratory findings revealed low insulin growth factor 1 (IGF-1) (15 ng/mL), elevated insulin growth factor 2 (IGF-2) (395 ng/ml), and an IGF-2:IGF-1 ratio of 26:1, consistent with NICTH. After ruling out other causes of hypoglycemia, including endocrine deficiencies and medication-induced hypoglycemia, the patient was managed with steroids and intravenous (IV) glucose. Due to the metastatic nature of the cancer, he was treated with atezolizumab and bevacizumab. Palliative radiation therapy (RT) was initiated to improve glycemic control. Following RT, hypoglycemic episodes decreased, allowing discharge with oral steroids. NICTH management remains challenging due to limited therapeutic options and variable treatment responses. Surgical resection is the standard treatment for NICTH; however, conservative approaches include steroid use, glucose supplementation, and recombinant growth hormone (GH). In this case, radiation was chosen to target the tumor and alleviate hypoglycemia, resulting in improved glycemic stability post-treatment. NICTH associated with HCC is a rare and challenging complication with significant morbidity. Early use of RT alongside systemic treatment may offer a viable strategy for managing NICTH and improving patient outcomes.