Hypoglycemia due to big IGF-2

• Published in: Acta clinica belgica (English ed. Online) 2016-03, Vol.71 (S2), p.3
• Main Authors: Carpentier, M, Van Huffel, L, Lapauw, B
• Format: Article
• Language: English
• Subjects: Consciousness; Diabetes; Hypoglycemia; Insulin; Tumors
• ISSN: 1784-3286; 2295-3337

Hypoglycemia is most commonly iatrogenic, caused by insulin or insulin secretagogue used to treat diabetes mellitus. Diagnosis and treatment of such an event is straightforward. By contrast, spontaneous hypoglycemia in a non-diabetic patient requires a thorough investigation. Hypoglycemia is confirmed when Whipple's triad is present. Clinical evaluation and biochemical work-up with insulin, proinsulin, c-peptide, circulating oral hypoglycemic agents, insulin antibodies and cortisol is needed. Treatment consists of correcting the glycemic state and specific therapy for the primary disease. A 59-year-old non-diabetic man presented on the emergency department of our hospital with confusion and impaired consciousness during a work meeting. First investigations revealed a marked hypoglycemia (36 mg/dl). After intravenous administration of glucose, consciousness and cognitive functions returned to normal. Since the resection of an intracranial solitary fibrous tumor a few months earlier, he did not feel very well with difficulties to concentrate. This improved with the ingestion of carbohydrates. His weight was thought to be stable, night sweats were reported. Further biochemical investigation showed a low insulin and undetectable c-peptide. Given these results and the history of a solitary fibrous tumor, a IGF-2 induced hypoglycemia was suspected. This was confirmed by a western immunoblot assay. Levels of growth hormone and IGF-1 were low, serum cortisol was normal. The patient tested negative for insulin antibodies. Imaging studies showed diffuse liver lesions but no primary tumor. Microscopic evaluation of a liver biopsy revealed a malignant hemangiopericytoma. Initially, there was a striking need of glucose supplementation to reach normoglycemia. Up to 900 mg intravenous glucose per 24 h was administered, on top of oral intake. This could be rapidly tapered after initiation of glucocorticoids (32 mg methylprednisolone). After reaching normoglycemia, making the diagnosis and staging, the patient was transferred to the department of oncology for initiation of chemotherapy with adriamycin. Tumors producing big IGF-2 are a known cause of spontaneous hypoglycemia. Big IGF-2 is an aberrant protein with a higher molecular mass, with low affinity for IGF binding proteins, and thus mainly acting on the insulin receptor causing hypoglycemia. These tumors are mainly benign (mostly benign solitary fibrous tumor), but a few are malignant (mostly malignant solitary fibro