Hypoglycemia Associated with the Production of Insulin-like Growth Factor II in a Pancreatic Islet Cell Tumor: A Case Report

Abstract

Abstract. An insulinoma is characterized by endogenous hyperinsulinemia and hypoglycemia. However, it has been reported that insulinomas with normal levels of plasma insulin and a normal insulin to glucose ratio occur in patients with hypoglycemia. Although overproduction of Insulin-like growth factor II (IGF-II) by non-islet cell tumors such as large mesenchymal tumors, can cause hypoglycemia, no cases of circulating plasma IGF-II from an islet cell tumor contributing to hypoglycemia have been reported. We report here a rare case of a pancreatic islet tumor in a patient with hypoglycemia that was associated with increased plasma IGF-II, which returned to normal after tumor resection. HYPOGLYCEMIA is a common medical condition with many causes. Although hypoglycemia is most common in patients with diabetes mellitus, it also occurs in patients with renal insufficiency, liver disease, congestive heart failure, autoimmune disorders or cancer [1]. An insulinoma, which is the most common type of islet cell tumor, is characterized by endogenous hyperinsulinemia and hypoglycemia [2]. However, insulinomas with normal levels of plasma insulin and a normal insulin to glucose ratio have been reported in hypoglycemic patients [3]. Insulin-like growth factor II is structurally and functionally related to insulin [4], and overproduction of IGF-II by non-islet cell tumors such as large mesenchymal or epithelial tumors, can cause hypoglycemia [5]. In addition, IGF-II also expressed by insulinproducing tumor cells in the pancreas, as well as some endocrine pancreatic tumors that also produce other peptides such as glucagons [6]. However, there have been no reports of circulating plasma IGF-II produced by islet cell tumor contributing to hypoglycemia.Here, we describe a rare case of a pancreatic islet cell tumor in a patient with hypoglycemia that was associated with increased plasma IGF-II levels, which returned to normal after tumor resection. Case ReportA 65-year old woman was admitted to our hospital after experiencing recurrent episodes of cold sweats and palpitation for 5 years. These symptoms developed when she was hungry or early in the morning, and then disappeared after eating. The incidence of these symptoms had gradually increased and she experienced general weakness and sweating the day before admission. At the time of admission, she was taking cilnidipine (10 mg/day) and irbesartan (150 mg/day) for arterial hypertension, and Hashimoto's thyroiditis had been detected 3 years prior to admission at our facility, but it was well-controlled without pharmacological treatment. She did not smoke or drink and had

Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor–2 from a malignant renal solitary fibrous tumor – clinical case and literature review

“…Pathologic diagnosis included solitary fibrous tumor (n = 10), hemangiopericytoma (n = 3), phyllodes tumor and sarcoma (n = 2), hepatocellular carcinoma (n = 2), uterine leiomyoma (n = 1), gastric adenocarcinoma (n = 1), ovarian germ cell tumor (n = 1), pheochromocytoma (n = 1) and desmoplastic small round cell tumor (n = 1). Hypoglycemia associated with IGF-2 production has also been reported in pancreatic islet cell tumor [39]. Biochemical profiles of the patients varied and included elevated IGF-2, elevated big IGF-2 with normal IGF-2, and elevated IGF-2 to IGF-1 ratio.…”

Retrospective Study of Canine Insulinomas: Eight Cases (2005-2008)

“…Insulinomas without abnormal plasma insulin levels have been reported in human medicine [5,7,8]. The mechanisms remain unclear, although several possible options must be considered: 1) insulinoma may secrete insulin in short bursts, causing wide fluctuations in plasma insulin levels; 2) insulinoma may secrete abnormal insulin, which is easily broken down; 3) insulinoma may release excessive amounts of proinsulin, which displays less biological potency than the corresponding insulin molecules; and 4) circulating insulin-like growth factor (IGF)-II may contribute to hypoglycemia [5].…”

“…The mechanisms remain unclear, although several possible options must be considered: 1) insulinoma may secrete insulin in short bursts, causing wide fluctuations in plasma insulin levels; 2) insulinoma may secrete abnormal insulin, which is easily broken down; 3) insulinoma may release excessive amounts of proinsulin, which displays less biological potency than the corresponding insulin molecules; and 4) circulating insulin-like growth factor (IGF)-II may contribute to hypoglycemia [5]. In addition, a subgroup of patients with insulinoma demonstrates elevated insulin levels as well as insulin secretion totally uncoupled from the blood glucose concentration [16].…”

Pancreatic neuroendocrine tumor with hypoglycemia and elevated insulin-like growth factor II: a case report

“…To date this is the second case reported of hypoglycemia due to production of IGF-II by a pNET. [10] This unusual case highlights the importance of taking into account the production of IGF-II in case of hypoglycemia and pancreatic lesion when clinical, biochemical, and immunohistochemical data are not consistent with insulinoma. In our patient, the finding of empty sella could have justified GH deficiency, so IGF-II was not immediately evaluated.…”