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      Non-islet cell tumor-induced hypoglycemia: a report of five cases and brief review of the literature

      case-report

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          Summary

          We describe the clinical presentation, diagnostic and management issues in five cases of non-islet cell tumor hypoglycemia (NICTH), diagnosed at a tertiary care institute over a period of 15 years. The clinical, laboratory, and histopathological findings of these patients along with diagnostic utility of IGF2:IGF1 ratio are discussed. The mean age of presentation was 52 years, with a male predominance (3:2). Three patients presented with recurrent episodes of fasting hypoglycemia and it was detected in other two patients during hospitalization. Two patients had acromegaloid features that regressed following treatment. One patient had hypokalemia. Low levels of insulin, C-peptide, GH, and IGF1 were invariably found in all. The IGF2 level was elevated in only one patient; however, IGF2:IGF1 ratio was more than 10 in four of the five patients. The mean tumor size was 16.4 cm and mean weight was 3.6 kg. Four patients had mesenchymal tumors and one had epithelial tumor. NICTH is a rare cause of hypoglycemia. Hypoinsulinemic hypoglycemia with low IGF1 and IGF2:IGF1 ratio more than 10 is suggestive of this entity.

          Learning points

          • NICTH should be considered in patients presenting with tumor of mesenchymal origin and hypoglycemia.

          • Hypoinsulinemic hypoglycemia with low IGF1 is a strong biochemical evidence of NICTH.

          • IGF2:IGF1 ratio of more than 10 is a complementary investigation in the absence of an assay facility for IGF2.

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          Most cited references11

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          Seminars in medicine of the Beth Israel Deaconess Medical Center. Insulin-like growth factors.

          Nhu D. Le (1997)
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            Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases.

            This review focuses on the tumour types and symptoms associated with non-islet cell tumour-induced hypoglycaemia (NICTH) as well as the pathogenesis, diagnosis and treatment of this rare paraneoplastic phenomenon. In addition, we report two illustrative cases of patients suffering from NICTH caused by a solid fibrous tumour and a haemangiopericytoma respectively. In the first case, NICTH resolved following complete resection of the tumour, but in the second case the patient needed long-term treatment aimed at controlling hypoglycaemia because of non-resectable metastases. Many tumour types have been associated with NICTH. The crucial event in the development of NICTH seems to be overexpression of the IGF-II gene by the tumour. NICTH is characterised by recurrent fasting hypoglycaemia and is associated with the secretion of incompletely processed precursors of IGF-II ('big'-IGF-II) by the tumour. This induces dramatic secondary changes in the circulating levels of insulin, GH, IGF-I and IGF-binding proteins, resulting in an insulin-like hypoglycaemic activity of 'big'-IGF-II.
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              Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia.

              In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62+/-1.8, range; 9-86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 microU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4+/-0.6 kg/m2) and serum total protein levels (6.6+/-0.1g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                edm
                EDM Case Reports
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                20 November 2013
                2013
                : 2013
                : 130046
                Affiliations
                [1 ]Department of Endocrinology Post Graduate Institute of Medical Education and Research Chandigarh, 160012India
                [2 ]Department of Histopathology Post Graduate Institute of Medical Education and Research Chandigarh, 160012India
                [3 ]Department of Radiodiagnosis Post Graduate Institute of Medical Education and Research Chandigarh, 160012India
                Author notes
                Correspondence should be addressed to A Bhansali Email: anilbhansaliendocrine@ 123456gmail.com
                Article
                EDM130046
                10.1530/EDM-13-0046
                3922193
                24616774
                a63a9203-c824-4397-8529-32ca0b8cdfc4
                © 2013 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 20 September 2013
                : 22 October 2013
                Categories
                Unique/Unexpected Symptoms or Presentations of a Disease

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