MANAGEMENT OF ENDOCRINE DISEASE: A clinical update on tumor-induced hypoglycemia

Abstract

Tumor-induced hypoglycemia (TIH) is a rare clinical entity that may occur in patients with diverse kinds of tumor lineages and that may be caused by different mechanisms. These pathogenic mechanisms include the eutopic insulin secretion by a pancreatic islet b-cell tumor, and also the ectopic tumor insulin secretion by non-islet-cell tumor, such as bronchial carcinoids and gastrointestinal stromal tumors. Insulinoma is, by far, the most common tumor associated with clinical and biochemical hypoglycemia. Insulinomas are usually single, small, sporadic, and intrapancreatic benign tumors. Only 5-10% of insulinomas are malignant. Insulinoma may be associated with the multiple endocrine neoplasia type 1 in 4-6% of patients. Medical therapy with diazoxide or somatostatin analogs has been used to control hypoglycemic symptoms in patients with insulinoma, but only surgical excision by enucleation or partial pancreatectomy is curative. Other mechanisms that may, more uncommonly, account for tumor-associated hypoglycemia without excess insulin secretion are the tumor secretion of peptides capable of causing glucose consumption by different mechanisms. These are the cases of tumors producing IGF2 precursors, IGF1, somatostatin, and glucagon-like peptide 1. Tumor autoimmune hypoglycemia occurs due to the production of insulin by tumor cells or insulin receptor autoantibodies. Lastly, massive tumor burden with glucose consumption, massive tumor liver infiltration, and pituitary or adrenal glands destruction by tumor are other mechanisms for TIH in cases of large and aggressive neoplasias.

Hypoglycemia Associated with a Gastrointestinal Stromal Tumor Producing High-molecular-weight Insulin Growth Factor II: A Case Report and Literature Review

“…Finally, identification of big-IGF-II confirmed the diagnosis. The absence of liver metastasis may have antagonized the hypoglycemia (14).…”

Síndromes paraneoplásicos en tumores gastrointestinales. Revisión de tema

“…Otros síndromes endocrinos asociados con tumores gastrointestinales son la acromegalia por elevación de la hormona de crecimiento y del factor insulínico de crecimiento tipo (IGF-1) (72). Los tumores más frecuentemente asociados son los gástricos y los pulmonares (63).…”

“…En mujeres con cáncer de colon, se ha encontrado producción ectópica de prolactina, que ocasiona galactorrea y amenorrea y, cuando se presenta en los hombres, produce ginecomastia e hipogonadismo (63). En tumores gástricos y estromales gastrointestinales (GIST), se ha encontrado hipoglucemia (72).…”

Appendix insulin secreting neuroendocrine tumor in a diabetic patient: a challenging diagnosis.

“…Tumor induced hypoglycemia (TIH) can rarely be developed by extra-pancreatic tumors and it can be due to insulin ectopic secretion or to other neuroendocrine pathogenic mechanisms such as IGF2, IGF1, somatostatin or GLP1 overproduction [2].…”

“…The majority of these rare tumors come from ectopic accessory or aberrant pancreas [3]. Anyway, anecdotal cases reported extra pancreatic insulin secreting tumors such as kidney neuroendocrine tumor, bronchial carcinoid, cervix carcinomas, paraganglioma, schwannomma, and gastrointestinal tumor [2].…”