Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases

    1. Winette T A van der Graaf4
    1. 1Department of Internal Medicine,, Isala Klinieken, Dr van Heesweg 2, 8025 AB Zwolle, The Netherlands 2Department of Metabolic and Endocrine Diseases,, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands 3Department of Internal Medicine,, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands 4Department of Medical Oncology,, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    1. (Correspondence should be addressed to J W B de Groot; Email:{at}


    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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