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¹ Department of Internal Medicine,, Isala Klinieken, Dr van Heesweg 2, 8025 AB Zwolle, The Netherlands ² Department of Metabolic and Endocrine Diseases,, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands ³ Department of Internal Medicine,, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands ⁴ Department of Medical Oncology,, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

(Correspondence should be addressed to J W B de Groot; Email: j.w.b.de.groot{at}isala.nl)

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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