Endocrine Abstracts

Background: Insulin like growth factor-2 (IGF-2) has structural similarity to insulin1. In excess, IGF-2 can activate glucose metabolism so precipitating hypoglycaemia1.

Case Presentation: Six days following her second dose of Doxorubicin and Olaratumab therapy for a pelvic sarcoma, HS presented with two successive days of acute confusion secondary to documented hypoglycaemia (blood sugars 2.0-3.1 mmol/l, 36-55.8 mg/dl). Despite treatment, she had recurrent symptomatic hypoglycaemia. She reported similar confusion episodes following the first cycle of chemotherapy 2 months previously. Initial investigations reported appropriate values for random cortisol, TSH and free T4. Further investigations revealed appropriately suppressed insulin and c-peptide that excluded insulinoma. The IGF-2 was elevated with an IGF-2:1 ratio of 25.9 (Normal Ratio<10). This was consistent with non-islet cell tumour hypoglycaemia. It was theorised that the chemotherapy related exacerbations were a consequence of tumour destruction and subsequent IGF-2 release. HS was managed with oral glucocorticoid therapy with symptomatic improvement and a documented reduction of hypoglycaemic events. She was discharged with blood sugar monitoring, dietary advice for frequent high sugar snacks and advice for hypoglycaemia treatment. Histology was reviewed for IGF-2 staining. With cautious steroid titration, HS was able to continue with her combined chemo-and immunotherapy regime.

Conclusions: This case reviews the common causes of non-diabetic hypoglycaemia, including immunotherapy-mediated hypoglycaemia (hypophysitis, thyroiditis and adrenal insufficiency). It focuses on an uncommon but well documented cause of recurrent hypoglycaemia; paraneoplastic IGF-2.

Reference: 1. A. Khowaja et al. Hypoglycaemia mediated by paraneoplastic production of Insulin like growth factor-2 from a malignant renal solitary fibrous tumor – clinical case and literature review. BMC Endocr Disord Jun 2014;14:49.