Hypoglycemia as a symptom of cancer in adults

Česká verzia

Authors: Zdeněk Fryšák; David Karásek
Authors place of work: III. interní klinika – nefrologická, revmatologická a endokrinologická LF UP a FN Olomouc
Published in the journal: Vnitř Lék 2016; 62(7-8): 564-567
Category: Reviews

Summary

Decrease of blood glucose levels below 3 mmol/l is in fully developed cases accompanied by neuroglycopenic symptoms that may even lead to altered state of consciousness. The treating physician frequently faces a complicated situation. This may be due to inappropriately administered drugs including cases motivated by self-harm intentions (insulin, insulin secretagogues), or alcohol abuse. Undernourished people, or those afflicted with a serious systemic infection, end-stage liver or kidney diseases or with a failing heart, belong to a risk group. Hypoglycemia typically accompanies hypocorticism (Addison‘s disease) or lack of glucagon. Endogenous hyperinsulinism caused by a hormonally active pancreatic cancer, that is, by a neuroendocrine tumour – insulinoma, is a possibility to be considered. A hidden cause of hypoglycemias may be a pancreatic-beta- cell dysfunction (nesidioblastosis, or non-insulin pancreatogenous hypoglycemia). A similar situation may arise following gastric bypass surgery. Hypoglycemia incited by the presence of antibodies to insulin or its receptor is cited in literature as a very rare problem. One section in the differentially diagnostic thinking is dedicated to hypoglycemic states accompanying neoplastic, malign processes. Insulin is demonstrably not a responsible agent here, it is a polypeptide structurally close to it, a somatomedin abbreviated as IGF2.

Key words:
endoscopic ultrasound pancreatography (EUPG) – hypoglycemia mediated by tumour cells other than β cells (NIPHS) – insulin-like growth factor (IGF1, IGF2) – pro-insulin-like growth factor IGF2 (pro-IGF2)

Zdroje

1. Whipple AO. The surgical therapy of hyperinsulinism. J Int Chir 1938; 3: 237.

2. Kong AP, Chan JC. Hypoglycemia and Comorbidities in Type 2 Diabetes. Curr Diab Rep 2015; 15(10): 80.

3. Cryer PE, Axelrod L, Grossman AB et al. Endocrine Society. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2009; 94(3): 709–728.

4. Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest 2007; 117(4): 868–870.

5. Boyle PJ, Schwartz NS, Shah SD et al. Plasma glucose concentrations at the onset of hypoglycemic symptoms in patients with poorly controlled diabetes and in nondiabetics. N Engl J Med 1988; 318(23): 1487–1492.

6. Frasca F, Pandini G, Scalia P et al. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol 1999; 19(5): 3278–3288.

7. de Groot JW, Rikhof B, van Doorn J et al. Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases. Endocr Relat Cancer 2007; 14(4): 979–993.

8. Hoekman K, van Doorn J, Gloudemans T et al. Hypoglycaemia associated with the production of insulin-like growth factor II and insulin-like growth factor binding protein 6 by a haemangiopericytoma. Clin Endocrinol (Oxf) 1999; 51(2): 247–253.

9. Zapf J, Futo E, Peter M et al. Can “big” insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia? J Clin Invest 1992; 90(6): 2574–2584.

10. Latifyan SB, Vanhaeverbeek M, Klastersky J. Tumour-associated osteomalacia and hypoglycaemia in a patient with prostate cancer: is Klotho involved? BMJ Case Rep 2014; 2014. pii: bcr2014206590. Dostupné z DOI: <http://dx.doi.org/10.1136/bcr-2014–206590>.

11. Service FJ. Hypoglycemic Disorders. N Engl J Med 1995; 332(17): 1144–1152.

12. Service FJ. Classification of hypoglycemic disorders. Endocrinol Metab Clin North Am 1999; 28(3): 501–517, vi.

13. Kann PH. Endoscopic Ultrasound in Endocrinology: Imaging of the Adrenals and the Endocrine Pancreas. Front Horm Res 2016; 45: 46–54.

14. Fu W, Li J, Wen J et al. Management of Islet Cell Tumours: A Single Hospital Experience. Hepatogastroenterology 2015; 62(139): 773–776.

15. Anlauf M, Wieben D, Perren A et al. Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis: diagnostic criteria, incidence, and characterization of beta-cell changes. Am J Surg Pathol 2005; 29(4): 524–533.

16. Thompson SM, Vella A, Thompson GB et al. Selective Arterial Calcium Stimulation With Hepatic Venous Sampling Differentiates Insulinoma From Nesidioblastosis. J Clin Endocrinol Metab 2015; 100(11): 4189–4197.

17. Thompson SM, Vella A, Service FJ et al. Impact of variant pancreatic arterial anatomy and overlap in regional perfusion on the interpretation of selective arterial calcium stimulation with hepatic venous sampling for preoperative localization of occult insulinoma. Surgery 2015; 158(1): 162–172.

18. Thompson GB, Service FJ, Andrews JC et al. Noninsulinoma pancreatogenous hypoglycemia syndrome: an update in 10 surgically treated patients. Surgery 2000; 128(6): 937–944; discussion 944–945.

19. Ahluwalia N, Attia R, Green A et al. Doege-Potter Syndrome. Ann R Coll Surg Engl 2015; 97(7): e105-e107. Dostupné z DOI: <http://dx.doi.org/10.1308/rcsann.2015.0023>.

20. Marks V, Teale JD. Tumours producing hypoglycaemia. Diabetes Metab Rev 1991; 7(2): 79–91.

21. Setoyama T, Miyamoto S, Horimatsu T et al. Bioactive insulin-like growth factors as a possible molecular target for non-islet cell tumor hypoglycemia. Cancer Biol Ther 2014; 15(12): 1588–1592.

22. Hizuka N, Fukuda I, Takano K et al. Serum insulin-like growth factor II in 44 patients with non-islet cell tumor hypoglycemia. Endocr J 1998; 45(Suppl): S61-S65.

23. Fukuda I, Hizuka N, Ishikawa Y et al. Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia. Growth Horm IGF Res 2006; 16(4): 211–216.

24. Chen DY, Stern SA, Garcia-Osta A et al. A critical role for IGF-II in memory consolidation and enhancement. Nature 2011; 469(7331): 491–497.

25. Thomas J, Kumar SC. Nonislet cell tumor hypoglycemia. Case Rep Endocrinol 2013; 2013: 308086. Dostupné z DOI: <http://dx.doi.org/10.1155/2013/308086>.

26. Du EH, Walshe TM, Buckley AR. Recurring rare liver tumor presenting with hypoglycemia. Gastroenterology 2015; 148(2): e11-e13. Dostupné z DOI: <http://dx.doi.org/10.1053/j.gastro.2014.09.036>

27. Ahluwalia N, Attia R, Green A et al. Doege-Potter Syndrome. Ann R Coll Surg Engl 2015; 97(7): e105-e107. Dostupné z DOI: <http://dx.doi.org/10.1308/rcsann.2015.0023>.

28. Kitada M, Yasuda S, Takahashi N et al. Non-islet cell tumor hypoglycemia caused by intrathoracic solitary fibrous tumor: a case report. J Cardiothorac Surg 2016; 11:49. Dostupné z DOI: <http://dx.doi.org/10.1186/s13019–016–0463–6>.

29. van Doorn J, Hoogerbrugge CM, Koster JG et al. Antibodies directed against the E region of pro-insulin-like growth factor-II used to evaluate non-islet cell tumor-induced hypoglycemia. Clin Chem 2002; 48(10): 1739–1750.

30. Teale JD, Marks V. Glucocorticoid therapy suppresses abnormal secretion of big IGF-II by non-islet cell tumours inducing hypoglycaemia (NICTH). Clin Endocrinol (Oxf) 1998; 49(4): 491–498.

31. Bourcigaux N, Arnault-Ouary G, Christol R et al. Treatment of hypoglycemia using combined glucocorticoid and recombinant human growth hormone in a patient with a metastatic non-islet cell tumor hypoglycemia. Clin Ther 2005; 27(2): 246–251.

32. Huang JS, Chang PH Refractory hypoglycemia controlled by systemic chemotherapy with advanced hepatocellular carcinoma: A case report. Oncol Lett 2016; 11(1): 898–900.