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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 3  |  Issue : 2  |  Page : 116-118

Intractable hypoglycemia in an elderly lady with breast cancer


Department of Medicine, Al Khor Hospital, Hamad Medical Corporation, Doha, Qatar

Date of Submission23-Jul-2018
Date of Acceptance10-Oct-2018
Date of Web Publication26-Dec-2018

Correspondence Address:
Dr. Khalid Farooqui
Hamad Medical Corporation, Doha
Qatar
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bjhs.bjhs_20_18

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  Abstract 


Paraneoplastic hypoglycemia is one of the rare causes of noninsulin-mediated hypoglycemia, which has been encountered mostly with solid tumors or mesenchymal in origin; however, it can also occur in patients with diverse kinds of tumor origin. Hypoglycemia related to tumors can be induced by different hormones produced by different tumors – for example, excessive secretion of insulin by islet cell tumors (insulinoma and neuroendocrine tumors); insulin-like growth factor 2 (IGF2) from mesenchymal and epithelial tumors; and rarely by secretion of IGF1, cytokines, and catecholamines or increased tumor metabolism of glucose. Herein, we report the case of an 89-year-old female, known to have type 2 diabetes mellitus with frequent hospital admission due to recurrent episodes of severe hypoglycemia, which was initially attributed to the insulin therapy she was taking; the patient continued to have episodes of hypoglycemia even after cessation of insulin. During her previous admission, she was found to have a swelling over the left breast. Ultrasound-guided biopsy was done and histopathology was suggestive of an invasive ductal cell breast carcinoma. We eventually found that these episodes of severe hypoglycemia were secondary to the paraneoplastic effect of invasive ductal cell carcinoma of the breast.

Keywords: Breast carcinoma, hypoglycemia, insulin-like growth factor 2, paraneoplastic hypoglycemia


How to cite this article:
Farooqui K, Abuzaid H, Hamammy R, Milad M. Intractable hypoglycemia in an elderly lady with breast cancer. BLDE Univ J Health Sci 2018;3:116-8

How to cite this URL:
Farooqui K, Abuzaid H, Hamammy R, Milad M. Intractable hypoglycemia in an elderly lady with breast cancer. BLDE Univ J Health Sci [serial online] 2018 [cited 2019 Jan 16];3:116-8. Available from: http://www.bldeujournalhs.in/text.asp?2018/3/2/116/248550



Paraneoplastic effect of tumors causing hypoglycemia was first described in 1930 by Doege in a case of mediastinal fibrosarcoma and is often caused by paraneoplastic secretion of big insulin-like growth factor 2 (IGF2) and is a rare syndrome among tumorous disease.[1] Paraneoplastic syndrome causing hypoglycemia is rarely seen in breast cancer and gynecological oncology.[2],[3],[4],[5] As per scientific literature available, only a few cases have been reported until now and no cases have been reported from the Indian subcontinent.[6] Hypoglycemia due to paraneoplastic effect is usually induced by an either a primary tumor which has huge bulk of tumor mass or seen in an advanced malignancy. It is mainly induced by paraneoplastic secretion of big IGF2 released from tumor mass, which competitively binds to insulin factor-binding proteins and exerts a similar action of insulin causing severe life-threatening hypoglycemia, simultaneously with negative feedback mechanism insulin, IGF1, and C-peptide secretion is decreased.[7],[8],[9],[10]

Therefore, paraneoplastic effect of tumor causing hypoglycemia could be the first sign of tumor progression or lead to the diagnosis of an unknown primary neoplasm.[9],[10] Intravenous administration of dextrose remains the mainstay of emergency treatment, and corticosteroids have shown promising results in suppressing IGF2 and reducing the frequency of hypoglycemic attacks.[11],[12]

We report this case of intractable hypoglycemia in an elderly lady which was discovered to be caused by the paraneoplastic effect of breast cancer.


  Case Report Top


This is an 89-year-old female who is known to have medical history relevant for essential hypertension, bronchiectasis, old cerebrovascular accident, and type 2 diabetes mellitus (T2DM). She has been on treatment for hypertension for the past 40 years, for diabetes mellitus on mixtard insulin for 42 years including basal insulin for the past (glargine) 7 years. Her initial treatment for diabetes was with oral hypoglycemic agents.

At the time of our evaluation, she was hospitalized multiple times (3 times in a span of 1 month) with severe hypoglycemia. Each time she was brought by her relatives to the emergency department with a history of drowsiness, excessive sweating, and restlessness, and a blood glucose level was suggestive of hypoglycemia. Her complaints were evaluated on those visits and were attributed to the insulin therapy. Although her treatment with insulin was withheld, she continued to present with hypoglycemia, and the lowest recorded blood glucose reading was 2.1 mmol/L.

She was treated with standard protocol for hypoglycemia, with dextrose infusion following which her random blood glucose raised to 7.4 mmol/L. However, despite withholding the insulin, she had repeated episodes of severe hypoglycemia over the next several hospital days.

On further evaluation, and with a suspicion of occult malignancy, physical examination revealed a soft-tissue swelling over the left breast. This swelling was confirmed by ultrasound (US), to be an irregular hypoechoic lesion with areas of calcification noticed in the 11–12 o'clock position of the left breast. There was vascularity seen within the lesion. The left axillary lymph node noticed was measured to be 1.5 cm × 1.1 cm. These findings were suggestive of a malignant lesion. Subsequently, an US-guided biopsy was performed, and the histopathology revealed an invasive ductal cell carcinoma (Grade 2/3).

The patient was kept on continuous infusion of dextrose as the patient had persistent low blood glucose readings. Meanwhile, the metabolic workup revealed insulin levels on the lower limit of normal range value, decreased C-peptide levels, normal IGF1 level, normal cortisol levels, and high normal IGF2, which in corelation with histopathological diagnosis of left breast tissue as invasive ductal cell carcinoma was clearly suggestive of paraneoplastic secretion of IGF2 causing recurrent hypoglycemic attacks [Table 1]. She was initiated on oral corticosteroids following which her blood glucose readings normalized. Reduction of tumor mass is found to be the only known effective treatment for paraneoplastic effect of tumor causing hypoglycemia. In this case of disseminated breast cancer, we referred the patient to a tertiary cancer center for further management.
Table 1: Laboratory findings

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  Discussion Top


An elderly lady known case of T2DM was hospitalized multiple times with recurrent hypoglycemic episodes for the past 1 month; since she was on basal insulin, her episodes were attributed to the insulin and it was promptly stopped, but despite discontinuing the insulin for more than a week, she was persistently having recurrent episodes of severe hypoglycemia over several days. During the course of hospitalization, she was found to have a swelling of the left breast, and US biopsy was suggestive of invasive ductal cell carcinoma of the left breast. Paraneoplastic hypoglycemia is a rare and life-threatening condition which is mainly due to huge bulk of the tumor mass and sometimes just the first manifestation of malignancy. In most cases, hypoglycemia caused by tumor mass is due to a paraneoplastic secretion of “big” IGF2,[3],[4] which is a partially processed precursor of IGF2. The abnormal IGF2 competitively binds by forming smaller complexes with IGF-binding proteins[5],[6],[7] and shows increased permeability and a higher bioavailability, and this is the reason we find that most patients with tumor-induced hypoglycemia exhibit IGF2 concentrations within normal ranges. The most effective, essential, lifesaving treatment for severe and persistent hypoglycemia is intravenous glucose administration. Infusion of glucagon is another treatment option as described by Hoff and Vassilopoulou-Sellin.[12] Initiation of glucocorticoids has been promising by correcting the growth hormone–insulin growth factor axis, stimulating gluconeogenesis and also in some cases by suppressing big IGF2 production. Hypoglycemia caused paraneoplastic secretion of IGF in breast cancer which is very rare and is described only in few patients in the literature.

Breast cancer is the most common malignancy in the world, more commonly seen in women of middle-aged, especially after menopause. Because of the tumor mass induced paraneoplastic secretion of IGF2 which behaves as insulin and acts on the insulin receptors causing severe hypoglycemia.[13],[14]

Learning point/take-home message

Intractable hypoglycemia in elderly population needs to be evaluated extensively to rule out the rare possibility of paraneoplastic etiology. Paraneoplastic hypoglycemia is at times the first sign of tumor progression or can lead to the diagnosis of an occult neoplasm. In the described case, the occult malignancy leading to intractable hypoglycemia was discovered to be an invasive ductal cell carcinoma.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Doege KW. Fibro-sarcoma of the mediastinum. Ann Surg 1930;92:955-60.  Back to cited text no. 1
    
2.
Bessell EM, Selby C, Ellis IO. Severe hypoglycaemia caused by raised insulin-like growth factor II in disseminated breast cancer. J Clin Pathol 1999;52:780-1.  Back to cited text no. 2
    
3.
Daughaday WH. Hypoglycemia in patients with non-islet cell tumors. Endocrinol Metab Clin North Am 1989;18:91-101.  Back to cited text no. 3
    
4.
Daughaday WH, Emanuele MA, Brooks MH, Barbato AL, Kapadia M, Rotwein P, et al. Synthesis and secretion of insulin-like growth factor II by a leiomyosarcoma with associated hypoglycemia. N Engl J Med 1988;319:1434-40.  Back to cited text no. 4
    
5.
Le Roith D. Tumor-induced hypoglycemia. N Engl J Med 1999;341:757-8.  Back to cited text no. 5
    
6.
Morbois-Trabut L, Maillot F, De Widerspach-Thor A, Lamisse F, Couet C. “Big IGF-II”-induced hypoglycemia secondary to gastric adenocarcinoma. Diabetes Metab 2004;30:276-9.  Back to cited text no. 6
    
7.
Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: Biological actions. Endocr Rev 1995;16:3-4.  Back to cited text no. 7
    
8.
Marks V, Teale JD. Tumours producing hypoglycaemia. Diabetes Metab Rev 1991;7:79-91.  Back to cited text no. 8
    
9.
Service FJ. Hypoglycemic disorders. N Engl J Med 1995;332:1144-52.  Back to cited text no. 9
    
10.
Daughaday WH, Kapadia M. Significance of abnormal serum binding of insulin-like growth factor II in the development of hypoglycemia in patients with non-islet-cell tumors. Proc Natl Acad Sci U S A 1989;86:6778-82.  Back to cited text no. 10
    
11.
Zapf J, Futo E, Peter M, Froesch ER. Can “big” insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia? J Clin Invest 1992;90:2574-84.  Back to cited text no. 11
    
12.
Hoff AO, Vassilopoulou-Sellin R. The role of glucagon administration in the diagnosis and treatment of patients with tumor hypoglycemia. Cancer 1998;82:1585-92.  Back to cited text no. 12
    
13.
Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, et al. Acritical role for IGF-II in memory consolidation and enhancement. Nature 2011;469:491-7.  Back to cited text no. 13
    
14.
Buckway CK, Wilson EM, Ahlsén M, Bang P, Oh Y, Rosenfeld RG, et al. Mutation of three critical amino acids of the N-terminal domain of IGF-binding protein-3 essential for high affinity IGF binding. J Clin Endocrinol Metab 2001;86:4943-50.  Back to cited text no. 14
    



 
 
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