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Case Reports
. 2019 May 15:10:316.
doi: 10.3389/fendo.2019.00316. eCollection 2019.

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

Vishnu Garla  1 , Hardik Sonani  2 , Venkatraman Palabindala  1 , Celso Gomez-Sanchez  1 , Jose Subauste  1 , Lillian Francis Lien  1
Affiliations
Case Reports

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

Vishnu Garla et al. Front Endocrinol (Lausanne). .

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.

Keywords: IGF-2 induced hypoglycemia; gastrointestinal stromal tumor; hepatocellular carcinoma; hypoglycemia; non-islet cell hypoglycemia.

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Figures

Figure 1
Figure 1
(A) Computed tomography (CT) of the abdomen showing a large mass of 20 cm size (red arrow). (B) CT of the abdomen showing a large tumor of 24 cm* 18 cm*12 cm (red arrow).
Figure 2
Figure 2
(A) Plasma glucose trend in case 1. (B) Plasma glucose trend in case 2.
Figure 3
Figure 3
(A) Spindle cells with fibrillary eosinophilic cytoplasm forming whorls consistent with gastrointestinal stromal tumor (GIST). (B) Diffuse positive staining to CD 117. (C) Immunohistochemistry showing diffuse positive staining to IGF-2 monoclonal antibody (MA5-17096, Thermofisher scientific Inc.). (D) No positive staining seen on the control for IGF-2 antibody (MA5-17096, Thermofisher scientific Inc.).
Figure 4
Figure 4
Synthesis and binding of mature and abnormal IGF-2.
Figure 5
Figure 5
Mechanisms by which IGF-2 induced hypoglycemia.
See this image and copyright information in PMC

References

    1. Cryer P. Hypoglycemia. In: Melmed S, Polonsky K., Braverman L, Kronenberg H, editors. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier; (2011). p. 1568.
    1. Teale JD, Wark G. The effectiveness of different treatment options for non-islet cell tumor hypoglycemia. Clin Endocrinol. (2004)60:457–60. 10.1111/j.1365-2265.2004.01989.x - DOI - PubMed
    1. Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. J Clin Endocrinol Metab. (2013)98:1845–59. 10.1210/jc.2012-4127 - DOI - PubMed
    1. Dynkevich Y, Rother KI, Whitford I, Qureshi S, Galiveeti S, Szulc AL, et al. Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive. Endocr Rev. (2013)34:798–826. 10.1210/er.2012-1033 - DOI - PubMed
    1. Nader W, Wolfer J. Hepatogenic hypoglycemia associated with primary liver cell carcinoma. Arch Intern Med. (1929)44:700–10. 10.1001/archinte.1929.00140050077007 - DOI

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