Big Insulin-like Growth Factor 2–Producing Tumor in a Hypoglycemic Dog

Abstract

A 10-year-old female Papillon dog that had previously developed a mammary tumor was admitted for treatment of a hypoglycemic attack. Blood examination showed severe hypoglycemia and decreased blood insulin concentration. Computed tomography indicated multiple tumors in the cranial and caudal lobes of the right lung. These tumors were resected surgically and diagnosed as pulmonary adenocarcinomas by histopathologic examination. Hypoglycemia was temporarily improved after the resection, but a hypoglycemic event occurred 2 months after the surgery. Immunohistochemistry of the tumor demonstrated the expression of insulin-like growth factor 2 in tumor cells. Western blot analysis revealed the expression of high-molecular-weight (big)–insulin-like growth factor 2 in the tumor region. Insulin-like growth factor 2 mRNA expression was also confirmed in the tumor using reverse transcription–polymerase chain reaction. These findings indicate the diagnosis of non–islet cell tumor-induced hypoglycemia caused by big-insulin-like growth factor 2 produced by the tumor in the dog. This report provides information on differentiating tumors that cause paraneoplastic hypoglycemia.

Rare Presentation of Hypoglycemia in a Patient with Anaplastic Large-Cell Lymphoma

“…Although we did not obtain bone marrow biopsy or insulin-like growth factors in the blood, we presumed that this hypoglycemia is most likely due to the anaplastic large-cell lymphoma because we did not find other alternative mechanisms of severe hypoglycemia in the patient such as sepsis, adrenal insufficiency, or insulinoma [ 13 ]. Furthermore, it is likely that such hypoglycemia may also be due to overproduction of insulin-like growth factor (IGF)-2 precursor protein, which is commonly known as “big insulin-like growth factor- (IGF-) 2” [ 16 ]. This is also supported by the literature whereby large neoplasms sometimes may produce IGF-2 that can circulate in the blood followed by binding to insulin and IGF receptors.…”

Validating Immunohistochemistry Assay Specificity in Investigative Studies: Considerations for a Weight of Evidence Approach

“…A combination of IHC, western blotting, and RT-PCR was used to confirm insulin-like growth factor 2 (IGF-2) expression in a pulmonary adenocarcinoma associated with hypoglycemia. 33 The authors further assessed insulin-like growth factor 1 (IGF-1) with each of these assays. By using 3 techniques to characterize IGF-2 expression and taking similar steps to rule out IGF-1, the authors were able to provide robust, nearly irrefutable evidence that tumor-derived IGF-2 was the cause of the hypoglycemia.…”

“…By using 3 techniques to characterize IGF-2 expression and taking similar steps to rule out IGF-1, the authors were able to provide robust, nearly irrefutable evidence that tumor-derived IGF-2 was the cause of the hypoglycemia. 33 In contrast to RT-PCR, ISH provides spatial information that can be directly correlated with IHC data. An example of this is the detection of West Nile virus in horses by IHC and ISH.…”

“…By using 3 techniques to characterize IGF-2 expression and taking similar steps to rule out IGF-1, the authors were able to provide robust, nearly irrefutable evidence that tumor-derived IGF-2 was the cause of the hypoglycemia. 33…”