Endocrine Abstracts

Case history: A 73-year-old gentleman was admitted for evaluation of recurrent hypoglycaemia. He has had type 1 diabetes mellitus for 60 years, which was well controlled on a basal-bolus regime with carbohydrate counting. He had frequent hypoglycaemic episodes for 5 months despite drastic reduction in insulin dosage. His insulin was completely stopped on admission. He did not develop ketosis and continued to have hypoglycaemia. He did not have end-organ complications from T1DM. Examination was unremarkable except for vitiligo.

Investigations: His venous glucose dropped to <2 mmol/l. Endocrinologic investigations revealed high levels of insulin like growth factor-2(IGF-2), suppressed insulin like growth factor-1(IGF-1), elevated IGF-2 : IGF-1 ratio with low insulin/C-peptide levels, which was consistent with non-islet cell tumour.

Results and treatment: CT thorax abdomen and pelvis revealed a massive right-sided pleural-based mass, occupying most of the lower right hemithorax. Biopsy after excision showed a fibrous tumour with abundance of spindle-shaped cells. There was no mitotic activity. It was positive for CD34, CD99, and vimentin on immunohistochemistry. The patient was given dietary counselling. He had successful surgical resection of the large solitary benign tumour with complete resolution of hypoglycaemic episodes.

Conclusions and points for discussion: This patient had recurrent hypoglycaemia due to a non-islet cell tumour (NICT). NICT is well described but we have not been able to find any reports of tumoural hypoglycaemia in a patient with established (>60 years) type 1 diabetes. Paraneoplastic phenomenon with spontaneous overproduction of IGF-2 can be seen in both mesenchymal and epithelial derived tumours such as fibromas, fibrosarcoma, gastrointestinal stromal tumours and hepatocellular tumours. Tumoural IGF-2 acted in a similar way to insulin, causing hypoglycaemia. Normally, IGF-2 binds to IGF-binding protein 3(IGFBP-3) and an acid-labile a-subunit forming a ternary complex. However, more than 60% of total IGF-2 in NICT is high-molecular weight (‘big IGF-2’) with low affinity to a-subunit, thus forming dimers. This smaller complex is easier to pass through capillary membrane and penetrate tissues, causing hypoglycaemia. Large quantities of big IGF-2 in NICT displace free IGF from IGFBP, increasing numbers of free IGF. Therefore, there is a direct relation between big IGF-2 and free total IGF-2 in NICT. The case was unique in that a patient with T1DM effectively became insulin-free. Surgery was still necessary because of the risks of recurrent hypoglycaemia. Hypoglycaemia resolved post-operatively and he resumed his basal-bolus insulin. He subsequently developed cognitive decline, which may be due in part to recurrent hypoglycaemia.