Non-islet Cell Hypoglycemia: Case Series and Review of the Literature

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2019 Jun 4

PMID 31156561

Citations 23

Authors

Vishnu Garla

Hardik Sonani

Venkatraman Palabindala

Celso Gomez-Sanchez

Jose Subauste

Lillian Francis Lien

Affiliations

Soon will be listed here.

Abstract

Non-islet cell hypoglycemia (NICH) is hypoglycemia due to the overproduction of insulin-like growth factor-2 (IGF-2) and its precursors which can activate the insulin receptor. Typically, large mesenchymal and epithelial tumors can cause NICH. Diagnosis is confirmed by finding an elevated IGF-2/IGF-1 ratio. The mainstay of treatment is surgical excision. Glucocorticoids may be used in cases where surgery is not possible. We present two cases of NICH with different outcomes. A 33-year-old male patient admitted with altered mental. He was found walking naked outside his house. Laboratory assessment revealed severe hypoglycemia. Further evaluation showed low levels of insulin, C-peptide, and beta-hydroxybutyrate along with an elevated IGF-2/IGF-1 ratio confirming the diagnosis of NICH. Computed tomography (CT) of the abdomen showed a massive tumor of the liver consistent with hepatocellular carcinoma. Since the patient refused surgery, he was started on prednisone however the hypoglycemia persisted. A 54-year-old female patient with a history of type 2 diabetes mellitus (DM) admitted with recent onset hypoglycemia. Despite stopping her insulin, she continued to have hypoglycemia necessitating the administration of high concentrations of intravenous dextrose. Further evaluation showed low levels of insulin, C-peptide, and beta-hydroxybutyrate along with an elevated IGF-2/IGF-1 ratio consistent with the diagnosis of NICH. CT abdomen showed a 24 cm tumor near the uterus. The pathology was consistent with a gastrointestinal stromal tumor (GIST). After surgical excision of the tumor, the hypoglycemia resolved.

Citing Articles

A Case of Nonislet Cell Tumor Hypoglycemia Due to Metastatic Salivary Myoepithelial Carcinoma.

Slack M, Sovich S, Sachs C, Martinez D, Yu R AACE Clin Case Rep. 2024; 10(5):184-187.

PMID: 39372824 PMC: 11447760. DOI: 10.1016/j.aace.2024.06.002.

Paraneoplastic hypoglycemia: An overview for optimal clinical guidance.

Karamanolis N, Kounatidis D, Vallianou N, Alexandropoulos K, Kovlakidi E, Kaparou P Metabol Open. 2024; 23:100305.

PMID: 39185033 PMC: 11342107. DOI: 10.1016/j.metop.2024.100305.

Recurrent Hypoglycemia in a 67-Year-Old Woman with CD5- Positive Diffuse Large B-Cell Lymphoma.

Zhang J, Qiu J, Wu L, Shen L, Gu Q, Tan W Clin Med Insights Case Rep. 2024; 17:11795476241271540.

PMID: 39148706 PMC: 11325302. DOI: 10.1177/11795476241271540.

Non-islet cell tumor hypoglycemia that required immediate surgery after a long-term asymptomatic state: recommendation for early intervention.

Kurihara T, Fujimoto K, Iwakura T, Hataya Y, Yamashita D, Matsuoka N Endocrinol Diabetes Metab Case Rep. 2024; 2024(3).

PMID: 39142329 PMC: 11378120. DOI: 10.1530/EDM-23-0148.

From liver to hormones: The endocrine consequences of cirrhosis.

Quiroz-Aldave J, Gamarra-Osorio E, Durand-Vasquez M, Rafael-Robles L, Gonzales-Yovera J, Quispe-Flores M World J Gastroenterol. 2024; 30(9):1073-1095.

PMID: 38577191 PMC: 10989500. DOI: 10.3748/wjg.v30.i9.1073.

References

Dizon A, Kowalyk S, Hoogwerf B . Neuroglycopenic and other symptoms in patients with insulinomas. Am J Med. 1999; 106(3):307-10. DOI: 10.1016/s0002-9343(99)00021-2. View

Rosenfeld R, Hwa V, Wilson E, Plymate S, Oh Y . The insulin-like growth factor-binding protein superfamily. Growth Horm IGF Res. 2000; 10 Suppl A:S16-7. DOI: 10.1016/s1096-6374(00)90007-8. View

Zapf J, Futo E, Peter M, FROESCH E . 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):2574-84. PMC: 443417. DOI: 10.1172/JCI116152. View

Frohman L, Downs T, Chomczynski P . Regulation of growth hormone secretion. Front Neuroendocrinol. 1992; 13(4):344-405. View

CROCKER D, Veith F . MESODERMAL TUMORS ASSOCIATED WITH HYPOGLYCEMIA: REVIEW OF LITERATURE AND REPORT OF A CASE. Ann Surg. 1965; 161:418-27. PMC: 1408962. DOI: 10.1097/00000658-196503000-00016. View

Sussenbach J, Steenbergh P, Holthuizen P . Structure and expression of the human insulin-like growth factor genes. Growth Regul. 1992; 2(1):1-9. View

Teale J, Wark G . The effectiveness of different treatment options for non-islet cell tumour hypoglycaemia. Clin Endocrinol (Oxf). 2004; 60(4):457-60. DOI: 10.1111/j.1365-2265.2004.01989.x. View

Cherrington A . The role of hepatic insulin receptors in the regulation of glucose production. J Clin Invest. 2005; 115(5):1136-9. PMC: 1087191. DOI: 10.1172/JCI25152. View

Qiu Q, Basak A, Mbikay M, Tsang B, Gruslin A . Role of pro-IGF-II processing by proprotein convertase 4 in human placental development. Proc Natl Acad Sci U S A. 2005; 102(31):11047-52. PMC: 1182422. DOI: 10.1073/pnas.0502357102. View

10.

Feng Y, Zhu Z, Xiao X, Choudhry V, Barrett J, Dimitrov D . Novel human monoclonal antibodies to insulin-like growth factor (IGF)-II that potently inhibit the IGF receptor type I signal transduction function. Mol Cancer Ther. 2006; 5(1):114-20. DOI: 10.1158/1535-7163.MCT-05-0252. View

11.

Fukuda I, Hizuka N, Ishikawa Y, Yasumoto K, Murakami Y, Sata A . Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia. Growth Horm IGF Res. 2006; 16(4):211-6. DOI: 10.1016/j.ghir.2006.05.003. View

12.

de Boer J, Jager P, Wiggers T, Nieboer P, Machteld Wymenga A, Pras E . The therapeutic challenge of a nonresectable solitary fibrous tumor in a hypoglycemic patient. Int J Clin Oncol. 2006; 11(6):478-81. DOI: 10.1007/s10147-006-0606-1. View

13.

Riedemann J, Macaulay V . IGF1R signalling and its inhibition. Endocr Relat Cancer. 2007; 13 Suppl 1:S33-43. DOI: 10.1677/erc.1.01280. View

14.

Prince S, Foulstone E, Zaccheo O, Williams C, Hassan A . Functional evaluation of novel soluble insulin-like growth factor (IGF)-II-specific ligand traps based on modified domain 11 of the human IGF2 receptor. Mol Cancer Ther. 2007; 6(2):607-17. DOI: 10.1158/1535-7163.MCT-06-0509. View

15.

Puglianiello A, Cianfarani S . Central control of glucose homeostasis. Rev Diabet Stud. 2007; 3(2):54-60. PMC: 1783580. DOI: 10.1900/RDS.2006.3.54. View

16.

de Groot J, Rikhof B, van Doorn J, Bilo H, Alleman M, Honkoop A . Non-islet cell tumour-induced hypoglycaemia: a review of the literature including two new cases. Endocr Relat Cancer. 2007; 14(4):979-93. DOI: 10.1677/ERC-07-0161. View

17.

Zapf J . Insulinlike growth factor binding proteins and tumor hypoglycemia. Trends Endocrinol Metab. 1995; 6(2):37-42. DOI: 10.1016/1043-2760(94)00144-s. View

18.

Cryer P, Axelrod L, Grossman A, Heller S, Montori V, Seaquist E . Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008; 94(3):709-28. DOI: 10.1210/jc.2008-1410. View

19.

Lawson E, Zhang X, Crocker J, Wang W, Klibanski A . Hypoglycemia from IGF2 overexpression associated with activation of fetal promoters and loss of imprinting in a metastatic hemangiopericytoma. J Clin Endocrinol Metab. 2009; 94(7):2226-31. DOI: 10.1210/jc.2009-0153. View

20.

Teale J, Marks V . Inappropriately elevated plasma insulin-like growth factor II in relation to suppressed insulin-like growth factor I in the diagnosis of non-islet cell tumour hypoglycaemia. Clin Endocrinol (Oxf). 1990; 33(1):87-98. DOI: 10.1111/j.1365-2265.1990.tb00469.x. View