E-Poster Presentation ESA-SRB-ANZBMS 2021

Non-islet cell tumour hypoglycaemia: a rare but serious paraneoplastic syndrome (#429)

Melisha Thambyaiyah 1 , Varun Manoharan 1 2 , Hamish Russell 1 2
  1. Diabetes and Endocrine Service, Liverpool Hospital, NSW
  2. South Western Sydney Clinical School, University of New South Wales, Sydney, NSW

A 79-year-old male presented with a reduced level of consciousness and hypoglycaemia with a background of metastatic sarcoma from a right lower lobe solitary fibrous tumour. Baseline blood tests revealed mildly raised inflammatory markers with normal thyroid function and cortisol level, no source of infection was localised. He responded well to prednisolone and 50% dextrose infusion, with complete resolution of neurological symptoms. Further investigation whilst hypoglycaemic revealed low insulin, c-peptide and beta-hydroxybutyrate in keeping with the diagnostic criteria for IGF-2 mediated hypoglycaemia, a subtype of non-islet cell tumour hypoglycaemia (NICTH).(1)

A rare but sinister complication of malignancy, NICTH is caused by tumour secretion of insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) or glucagon like peptide (GLP 1).(2) As in the case of our patient with a presumed diagnosis of IGF-2 mediated hypoglycaemia, mesenchymal tumours are most commonly associated.(3) IGF-2 induces hypoglycaemia through multiple actions. Gluconeogenesis, glycogenolysis, ketogenesis, lipolysis and activity of glucose 6 phosphatase are all inhibited. Additionally, IGF-2 increases glucose demands by muscles.(4) These metabolic pathways are stimulated by IGF-2 as the amino acid polypeptide shares 47% sequence homology with insulin.(5)

Clinically, patients with paraneoplastic production of IGF-2 generally present with neuroglycopaenic symptoms.(6) Biochemical evaluation at the time of hypoglycaemia reveal decreased levels of insulin, proinsulin, C-peptide and beta-hydroxybutyrate.(1) IGF-1 and IGF-2 levels can be measured, typically resulting in a raised IGF-2 to IGF-1 ratio.(4)  In the case of our patient, IGF-2 could not be tested as no Australian lab performs this assay. Following initial correction of hypoglycaemia, optimal long term therapy is surgical resection of the causative tumour which can result in cure. Medical therapy may be used for symptom relief when targeted treatment of malignancy is not feasible. This includes glucocorticoid, recombinant human growth hormone (rhGH) and glucagon use.(7)

  1. Cryer, P., Axelrod, L., Grossman, A. and Heller, S., 2009. Evaluation and management of adult hypoglycaemic disorders: an Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology and Metabolism, 94(3), p.709
  2. Iglesias, P. and Diez, J., 2014. Management of endocrine disease: a clinical update on tumor-induced hypoglycemia. European Journal of Endocrinology, 170(4), pp.147-57.
  3. Santos-Aguilar, R., Chavez-Villa, M., Contreras, A. and Garcia-Herrera, J., 2019. Successful Multimodal Treatment of an IGF2-Producing Solitary Fibrous Tumor With Acromegaloid Changes and Hypoglycemia. Journal of the Endocrine Society, 8(3), pp.537-543.
  4. Garla, V., Sonani, H. and Palabindala, V., 2019. Non-islet cell hypoglycaemia: Case series and review of the literature. Frontiers in Endocrinology, (10), p.316.
  5. Khowaja, A., Johson-Rabbett, B. and Bantle, J., 2014. Hypoglycemia mediated by paraneoplastic production of Insulin like growth factor–2 from a malignant renal solitary fibrous tumor – clinical case and literature review. BMC Endocrine Disorders, (14), p.49.
  6. Fukuda, I., Hizuka, N., Ishikawa, Y., Yasumoto, K., Murakami, Y., Sata, A., Morita, J., Kurimoto, M., Okubo, Y. and Takano, K., 2006. Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia. Growth Hormone & IGF Research, 16(4), pp.211-216.
  7. Bodnar, T., Acevedo, M. and Pietropaolo, M., 2014. Management of Non-Islet-Cell Tumor Hypoglycemia: A Clinical Review. The Journal of Clinical Endocrinology & Metabolism, 99(3), pp.713-722.