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ORIGINAL ARTICLE
Year : 2015  |  Volume : 12  |  Issue : 3  |  Page : 104-106

Serum adenosine deaminase activity in thyroid disorders


Department of Biochemistry, Bishweshwar Prasad Koirala Institute of Health Sciences, Dharan, Nepal

Date of Web Publication16-Oct-2015

Correspondence Address:
Dr. Seraj Ahmed Khan
Department of Biochemistry, Bishweshwar Prasad Koirala Institute of Health Sciences, Dharan - 56700
Nepal
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-0354.157933

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  Abstract 

Context: It has been widely reported that thyroid gland is very much prone to autoimmune disorder. Adenosine deaminase (ADA), an enzyme distributed in the human tissues, is considered as nonspecific marker of cell-mediated immunity. Also it is suggested to be an important enzyme for modulating the bioactivity of thyroid hormones, but its clinical significance in thyroid disorders is not yet characterized. Therefore this study aims to see association between serum ADA and different thyroid disorders if any. Research Design and Methods: This was a hospital based cross sectional study conducted in Immunoassay laboratory of Department of Biochemistry, BPKIHS. A total of 122 subjects were selected and divided into five groups: Group 1 (Euthyroid), Group 2 (Overt Hyperthyroid), Group 3 (Subclinical Hyperthyroid), Group 4 (Overt Hypothyroid) and Group 5 (Subclinical Hypothyroid) based on the thyroid function status. Samples were stored at − 20 o till the assay of parameters. Thyroid hormones; thyroxine (fT4), triiodothyronine (fT3) and thyroid stimulating hormones (TSH) were assayed by Enzyme Linked Immunoflouresent Assay (ELFA) technique. Serum ADA activity was estimated by spectrophotometric methods of Giusti and Galanti. Data are presented as mean ± SD. Statistical analysis done by Chi-square test and one way ANOVA. P <0.05 considered as significant. Result: Out of 122 subjects 91 were female and 31 were male, showing the female preponderance of thyroid disorders. There was significant difference in ADA activity in different thyroid disorders (P < 0.001). Conclusion: The females were more prone to thyroid disorders and there was significant difference in ADA activity in different thyroid disorders. Our findings suggest that ADA may play a role in the pathophysiology of thyroid disorders, however a large scale study is required to predict the relationship.

Keywords: Adenosine deaminase, thyroid disorder, thyroid hormones


How to cite this article:
Duwal R, Khan SA, Das BK, Gelal B. Serum adenosine deaminase activity in thyroid disorders. Thyroid Res Pract 2015;12:104-6

How to cite this URL:
Duwal R, Khan SA, Das BK, Gelal B. Serum adenosine deaminase activity in thyroid disorders. Thyroid Res Pract [serial online] 2015 [cited 2019 Sep 15];12:104-6. Available from: http://www.thetrp.net/text.asp?2015/12/3/104/157933


  Introduction Top


The thyroid gland produces hormones that are responsible for appropriate energy levels and an active life. At the same time, they are highly vulnerable to autoimmune diseases. Complex autoimmune diseases demonstrate a lack of tolerance to self-antigens, whereby autoreactive lymphocytes and/or antibodies mount an inflammatory response against various tissues in an individual. The response may be organ-specific, such as type 1 (insulin-dependent) diabetes mellitus (T1DM), Graves' disease, autoimmune hypothyroidism and multiple sclerosis, or non-organ specific, such as systemic lupus erythematosus, rheumatoid arthritis, juvenile chronic arthritis, psoriasis and inflammatory bowel disease. [1]

Adenosine deaminase (ADA), an enzyme distributed in the human tissues, [2] that converts adenosine into inosine through an irreversible deamination reaction, considered as good marker of cell-mediated immunity. [3] It plays a crucial role in lymphocyte proliferation and differentiation [4] , and shows its highest activity in T-lymphocytes. [5] ADA is considered as a non-specific marker of T-cell activation but its connection with the immune system is not yet established in thyroid disorders. Even though there are some reports [6] available on adenosine deaminase levels in thyroid diseases subjects, these are all inconclusive and controversial. Since a relationship exists between adenosine deaminase and cell-mediated immunity. [3] Therefore this preliminary study was undertaken to determine plasma ADA activity and sought out its association with various thyroid disorders.


  Materials and Methods Top


Study design

This was a hospital based cross sectional study. A total of122 subjects were enrolled from the patients visiting immunoassay lab of the teaching hospital for their thyroid function test after taking their informed consent. Five milliliter venous blood sample was collected aseptically in a plain vial and serum was separated after running it in centrifuge (REMI) at 3000 rpm for 10 minutes. Sample were stored at − 20°C till the analysis of thyroid hormones, TSH and ADA. Patients with liver disorders, renal disorders, congestive cardiac failure; pregnant women; patients on oral contraceptive pills, statins, and other medications that alter thyroid functions and lipid levels were excluded from the study.

Biochemical Assay

Thyroid hormones; fT4, fT3 and TSH were assayed by ELFA technique from VIDAS (bioMeriux RCSL 673 620 399). The normal reference values as per our laboratory were as follows: TSH (0.25-5.0 μIU/ml), fT3 (4.0-8.3 pmol/L), and fT4 (9.0-20.0 pmol/L). Serum ADA activity was measured by simple, sensitive spectrophotometer methods of Giusti and Galanti based on modified Berthelot's reaction. [7] Adenosine deaminase hydrolyses adenosine to ammonia and inosine. The ammonia formed further reacts with a phenol and hypochlorite in an alkaline medium to form a blue colored indophenol complex, with sodium nitroprusside acting as a catalyst. The intensity of blue colored indophenol complex formed is directly proportional to the amount of ADA present in the sample.

Division of the subjects

Study population were divided into five groups based on their thyroid reports. Patients with normal TSH, fT3, and fT4 were considered euthyroid (Group 1). Patients with low TSH and high fT3 and fT4 levels were classified as being overt hyperthyroid (Group 2). A low serum TSH level and normal fT3 and fT4 levels were required for the diagnosis of subclinical hyperthyroidism (Group 3). Patients with high TSH and low fT3 and fT4 levels were classified as being overt hypothyroid (Group 4). A high serum TSH level and normal fT3 and fT4 levels were required for the diagnosis of subclinical hypothyroidism (Group 5).

Statistical analysis

Data were expressed as frequency, percentage and mean ± standard deviation (SD). Statistical analysis was performed using the SPSS statistical program version 15.0 for Windows (SPSS Inc., Chicago, IL, USA). Chi-square test was used to compare the categorical data and one way ANOVA and Post Hoc Turkey HSD was used for nominal data. A P < 0.05 was considered to be statistically significant.


  Results Top


Of the 122 patients in the study group, 91 were females and 31 were males. The baseline characteristics of the study participants is depicted in [Table 1]. It is clear from the table that females were more prone to thyroid disorders as compared to males in all the groups. In the study group overt hyperthyroids were highest and subclinical hyperthyroid were lowest in number. [Table 2] shows the mean level of FT3, FT4, TSH and ADA in the study participants. The ADA activity was highest in overt hyperthyroids compared to other groups as shown in the [Table 2]. Comparison of ADA in different study groups is compared in [Figure 1], and we found a significant difference between Group 1 and Group 2, 4. The difference between Group 2 and Group 3, 4, 5 is also significant (P < 0.001). There was a significant difference in ADA level between the different study groups.
Figure 1: Comparison of serum ADA amongst the groups. *significant as compare to Group 2 and 4. significant as compare to Group 3, 4 and 5

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Table 1: Age and sex distribution of subjects in different groups


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Table 2: Thyroid profile and ADA in different groups


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  Discussion Top


Immunological disturbances of cell-mediated origin are believed to initiate from T-lymphocyte dysfunction. ADA plays a crucial role in lymphocyte proliferation and differentiation [5] and shows its highest activity in T-lymphocytes. [6] In the present study we studied the ADA activity in different thyroid disorders that is euthyroid, overt hyperthyroid, subclinical hyperthyroid, overt hypothyroid and subclinical hypothyroid. Since this is the first study of its kind therefore very few literature are available. Similar study has been carried out in other disorders like diabetes mellitus (DM), autoimmune diseases, tuberculosis. Our study report that the females are much prone to thyroid disorders as compare to male, owing to their greater susceptibility to increased autoimmunity.

ADA level was found to be significantly higher in overt hyperthyroid and overt hypothyroid as compared to normal euthyroid subjects. Our finding is in accordance to the study done by Abbas et al. [7] Whereas the study done by Vishnu et al., [8] shows that ADA level in hyperthyroid patients were within normal limit, which contradicts to our study. We also noted significant difference in ADA level between Group 2 and Group 3, 4, 5. We could not find any report that shows such relation because of the limited studies done in this area. However there are many studies done in diseases like DM showing significant increase in ADA level in DM. [9],[10],[11],[12],[13]

As our findings suggests that there is increase in the serum level of ADA in overt hyper and hypothyroid patients therefore its altered blood levels may help in predicting immunological dysfunction in thyroid disorders and might be one of the important biomarkers in predicting the disease. However further investigations are necessary for the clarification of pathogenic role of ADA in thyroid diseases.

 
  References Top

1.
Heward J, Gough SC. Genetic susceptibility to the development of autoimmune disease. Clin Sci (Lond) 1997;93:479-91.  Back to cited text no. 1
[PUBMED]    
2.
Vader Weyden MB, Kelly WN. Human adenosine deaminase. Distribution and properties. J Biol Chem 1976;251:5448-56.  Back to cited text no. 2
    
3.
Baghanha MF, Pego A, Lima MA, Gaspar EV, Cordeiro AR. Serum and pleural adenosine deaminase correlation with lymphocyte populations. Chest 1990;87:605-10.  Back to cited text no. 3
    
4.
Hovi T, Smyth JF, Allison AC, Williams SC. Role of adenosine deaminase in lymphocyte proliferation. Clin Exp Immunol 1976;23:395-403.  Back to cited text no. 4
[PUBMED]    
5.
Sullivan JL, Oxborne WR, Wedgewood RJ. Adenosine deaminase activity in lymphocytes. Br J Haematol 1977;37:157-8.  Back to cited text no. 5
    
6.
Giusti G, Galanti B. Colorimetric method: Adenosine deaminase. In: Bergmeyer HU, editor. Methods of enzymatic analysis. Vol 4, 3 rd edition. Weinhem: Verlag Chemie; 1984. p. 315-23.  Back to cited text no. 6
    
7.
Abbas AK, Kadhim FH, Waheeb ZT. A study on the relationship between thyroid hormones and adenosine deaminase enzyme activity in patients with auto- immune hyperthyroid disease. Iraqi Post Med J 2008;7:164-7.  Back to cited text no. 7
    
8.
Vishnu M, Sampath KV, Mohanty S. Role of ADA in immunological disorders - Diabetes mellitus and thyroid dysfunction. J Health Sci 2013.  Back to cited text no. 8
    
9.
Lee JG, Kang DG, Yu JR, Kim Y, Kim J, Koh G, et al. Changes in adenosine deaminase activity in patients with type 2 diabetes mellitus and effect of dpp-4 inhibitor treatment on ADA activity. Diabetes Metab J 2011;35:149-58.  Back to cited text no. 9
    
10.
Khemka VK, Bagchi D, Ghosh A, Sen O, Bir A, Chakrabarti S, et al. Raised serum adenosine deaminase level in nonobese type 2 diabetes mellitus. ScientificWorldJournal 2013;2013:404320.  Back to cited text no. 10
    
11.
Kurtul N, Pence S, Akarsu E, Kocoglu H, Aksoy Y, Aksoy H. Adenosine deaminase activity in the serum of type 2 diabetic patients. Acta Medica (Hradec Kralove) 2004;47:33-5.  Back to cited text no. 11
    
12.
Hoshino T, Yamada K, Masuoka K, Tsuboi I, Itoh K, Nonaka K, et al. Elevated adenosine deaminase activity in the serum of patients with diabetes mellitus. Diabetes Res Clin Pract 1994;25:97-102.  Back to cited text no. 12
    
13.
Prakash MS, Chennaiah S, Murthy YS, Anjaiah E, Rao SA, Suresh C. Altered adenosine deaminase activity in type 2 diabetes mellitus. J Indian Acad Clin Med 2006;7:114-7.  Back to cited text no. 13
    


    Figures

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    Tables

  [Table 1], [Table 2]



 

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