Paraneoplastic hypoglycemia is a rare but clinically significant complication observed in patients with various malignancies. It is frequently associated with tumors that secrete insulin‑like growth factors, particularly insulin‑like growth factor 2 (IGF‑2). IGF‑2 and its precursors interfere with glucose homeostasis by promoting excessive glucose uptake and utilization by peripheral tissues. The role of IGF‑2 in tumorigenesis is attributed to its capacity to link high energy intake with enhanced cellular proliferation and inhibition of apoptosis. Notably, IGF‑2 overexpression has been correlated with chemoresistance and poorer clinical outcomes.¹

An extensive range of tumors, such as vascular, epithelial, or mesenchymal‑origin tumors, have been previously described as associated with paraneoplastic hypoglycemia.² The most common are hepatocellular carcinomas, followed by adrenocortical tumors, mesotheliomas, and fibrosarcomas.² There are 2 main approaches to the treatment of paraneoplastic hypoglycemia. Causal treatment consists of surgical removal or pharmaceutical intervention directed at the underlying tumor. In the cases where specific treatment is not feaseble, conservative measures, such as corticotherapy, glucagon, intravenous glucose, or dietary precautions, aimed exclusively at managing hypoglycemia, are used.³

We present a case of a 75‑year‑old woman with a documented history of pleural and right lung fibrosarcoma, initially treated with atypical resection of the upper, middle, and lower lobes of the right lung in 2013, currently exhibiting local progression managed with best supportive care, and non‑Hodgkin lymphoma in complete remission since the completion of therapy in 2022.

The patient was initially admitted to a neurological ward with symptoms of confusion and recurrent falls, primarily occurring during early morning hours. Intracranial pathology was ruled out as a contributing factor during the initial hospital assessment. Due to repeated episodes of severe hypoglycemia (plasma glucose levels ranging from 1.2 to 3 mmol/l; reference range [RR], 3.9–5.6 mmol/l), the patient was subsequently transferred to an internal medicine ward for further diagnostic evaluation and management.

According to her medical history, the patient had no prior diagnosis of prediabetes or diabetes mellitus and had never been treated with insulin, sulfonylurea derivates, or other hypoglycemia‑inducing agents. Her ongoing medical treatment included management of hypercholesterolemia and hypothyroidism, and she had a known history of sigmoid diverticulosis. Surgical history (with the exception of the already mentioned lung lobectomy) included cholecystectomy (1977), appendectomy (1983), and strumectomy (2022).

During hospitalization in our ward, the patient experienced recurrent hypoglycemic episodes without loss of consciousness, despite the implementation of dietary modifications and parenteral glucose infusions. Laboratory evaluation showed markedly low C‑peptide levels (72 pmol/l; [RR], 260–1730 pmol/l), while morning serum cortisol was normal (404 nmol/l; RR, 133–537 nmol/l). Clinical suspicions of insulinoma, adrenocortical insufficiency, and factitious disorder (Munchausen syndrome) were subsequently excluded. Due to mild hypothyroidism, which may exacerbate the symptoms of hypoglycemia, the dose of thyroid hormone substitution was adjusted.

As normoglycemia could not be maintained through specialized dietary modifications and glucose infusions alone, parenteral nutrition was initiated. However, the patient’s state and home conditions did not allow for safe administration of home parenteral nutrition. Therefore, the treatment strategy had to be changed. Corticosteroid therapy with prednisone (25 mg daily) and evening administration of corn starch (6 Tablespoons dissolved in 200 ml of water) were introduced to stabilize blood glucose levels. Subsequently, glycemic control was satisfactory with this regimen, eliminating the need for ongoing parenteral nutrition. The patient was discharged with arrangements for home care, continuing both corn starch supplementation and corticosteroid therapy.

The patient received comprehensive education regarding regular blood glucose monitoring and management of potential hypoglycemic episodes, with additional instructions provided to her family. A dietitian advised on an appropriate diet, incorporating a high‑protein oral nutrition supplements (14.6 g protein per 100 ml) as part of the nutritional plan.

The diagnosis of paraneoplastic hypoglycemia presents a clinical challenge, typically requiring confirmation of symptomatic hypoglycemia, exclusion of alternative etiologies, and evidence of an underlying malignancy. Diagnostic evaluation often involves laboratory assessments, including measurements of insulin, C‑peptide, cortisol, IGF‑2 levels, and the IGF‑2/IGF‑1 ratio, complemented by appropriate imaging studies. Currently, IGF‑2 quantification is not available in standard hospital laboratories in the Czech Republic. At present, we perform IGF‑2 measurement in collaboration with the Czech Centre for Phenogenomics. Efforts are ongoing to establish IGF‑2 assay capabilities within our hospital laboratory to facilitate in‑house testing.

IGF 2 in the blood is bound to specific binding proteins. In patients with fibrosarcoma, IGF‑2 more frequently forms binary complexes with IGF binding protein‑3 (IGFBP‑3) in the bloodstream. In healthy subjects, IGF 2 is more likely to form tertiary complexes with IGFBP‑3 and the acidolabile subunit. The binary complexes are smaller and more easily penetrate the capillary wall, which increases their bioavailability and hypoglycemic effect realized through the insulin receptor. As understanding of the mechanisms of paraneoplastic hypoglycemia evolves, new treatment modalities are being developed. One potentially promising approach is the development of high‑affinity antibodies targeting IGF‑2.⁴ However, even drugs commonly available to us, such as corticosteroids, may be useful in suppressing IGF‑2 production.³

Corn starch has long been established as a cornerstone therapy for patients with glycogen storage disease type Ia.⁵ Due to glucose‑6‑phosphatase deficiency, these patients experience severe hypoglycemia during extended fasting periods. In this case, we utilized the slow glucose‑release properties of corn starch to prevent nocturnal hypoglycemia and maintain euglycemia overnight.

The patient’s prognosis remains uncertain; however, the therapeutic intervention with corticosteroids and corn starch resulted in a marked improvement in her quality of life, which had previously been significantly compromised by frequent hypoglycemic episodes, thereby facilitating discharge to home care. The patient continues to be closely monitored in our outpatient clinic, with regular assessments of blood glucose levels, which have remained within normal limits.

This case contributes valuable insights into the challenges of diagnosing and managing paraneoplastic hypoglycemia. Enhanced understanding of the differential diagnostic process will support more informed clinical decision‑making for future patients presenting with suspected paraneoplastic hypoglycemia in the Czech Republic.