Abstract
Background:
Anti-TPO antibodies are one of the characteristic factors in autoimmune thyroiditis (AIT). Previous studies reported a high prevalence of anti-TPO antibodies (Abs) in Iran. We have therefore assessed the prevalence of anti-TPO Abs in Gorgan, Iran.
Methods:
This cross-sectional study, conducted from 2015 to 2018 in Gorgan city, Northeast of Iran. The Participants included women with Poly cystic ovary syndrome (PCOs), celiac patients, men with hepatitis C infection, and age and sex-matched controls. ELISA method was used for the analysis of laboratory tests.
Results:
The number of enrolled subjects in PCOs, celiac disease, and Hepatitis C infection groups were 76, 67, and 60, respectively. Anti-TPO Abs positivity was significantly higher in patients with PCOS than in the control group (18.4% vs. 0.00%; p = 0.000). There were no significant differences in the frequency of anti-TPO Abs positive cases between CD patients and the controls (26.9% vs. 21.1% p =0.413). The incidence of anti-TPO Abs positivity was significantly higher in the control group (10% vs. 25%; P = 0.031).
Conclusion:
Very high level of anti-TPO Abs was observed in both patients and healthy population in Golestan province. Considering this rate and its association with autoimmune disorders, it is suggested to prioritize screening programs for related disease in this area.
Key Words: Anti-thyroid Peroxidase (anti-TPO), Autoimmune thyroiditis (AIT), Celiac disease, Hepatitis C infection, Iran
The thyroid gland is the most common site of autoimmune diseases (1). Autoimmune thyroiditis (AIT) is characterized by anti-Thyroid peroxidase (anti-TPO) and anti-Thyroglobulin (anti-Tg) autoantibodies (2). The prevalence of thyroid dysfunction in a different population depends on geographic/environmental factors, sex, age, ethnicity, etc (3,4). Previous studies in Iran reported a high prevalence of anti-TPO antibodies (Abs) either in patients with specific disorders or in the general population (5–8). We have therefore assessed the prevalence of anti-TPO Abs in women with polycystic ovarian syndrome (PCOS), male with hepatitis C and celiac patients (CD) compared to the control group.
Methods
This cross-sectional study, conducted from 2015 to 2018 in Gorgan city, Northeast of Iran. The Participants included 1) Women with confirmed PCOs with diagnostic criteria such as oligoovulation, anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries at ultrasonography (9).
The control group included healthy age and sex-matched women who visited gynecology clinics for other gynecological concerns except for POCS and AIT; 2) Celiac patients diagnosed with positive serological tests for tissue transglutaminase (TTG) antibodies, followed by an intestinal biopsy (10). The control group included healthy age and sex-matched patients who visited gastroenterology clinics for other concerns except for CD, AIT, and no IgA deficiency; 3) Men recently diagnosed with hepatitis C using a rapid HCV antibody test and PCR method (11). The control group included healthy age and sex-matched men who visited gastroenterology clinics for other concerns except HCV, AIT, with no history of being in prison, addiction to IV drugs, and positive HBsAg. Anti-TPO Abs was checked with an ELISA method in the same laboratory.
The local ethical committee of the Golestan University of Medical Sciences approved the protocol (IR.GOUMS.REC.1398.164).
Results
The PCOs patients consisted of 76 women with a mean age of 26.62±5.58 years. In the control group, there were 66 females. PCOS was diagnosed based on oligoovulation in 61 patients (85.9%), polycystic ovaries at ultrasonography in 48 (67.7%), clinical or biochemical hyperandrogenism in 26 (36.6%), and anovulation in 22 (31%). Anti-TPO Abs positivity was significantly higher in patients with PCOS than in the control group (p = 0.000) (table 1). In the CD patients, there were 18 males and 49 females with a mean age of 38.65±11.48 years. The control group consisted of 28 males and 57 females. There were no significant differences in the frequency of anti-TPO Abs positive cases between CD patients and the control (p =0.413) (table 1). Hepatitis C patients consisted of 60 men with a mean age of 41.17±8.033 years. In the control group, there were 60 men. The incidence of anti-TPO Abs positivity was significantly higher in the control group (P = 0.031) (table 1).
Table 1.
Anti-thyroid Peroxidase (anti-TPO) positive rate and median in polycystic ovarian syndrome (PCOS), Celiac disease (CD), and hepatitis C infection, and control groups
| PCOs | CD | Hepatitis C infection | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Case (N:76) | Control (N:66) | P-value | Case (N:67) | Control (N:85) | P-value | Case (N:60) | Control (N:60) | P-value | |
|
Positive Anti-TPO,
N (%) |
14 (18.4%) | 0 (0%) | 0.000 | 18 (26.9%) | 18 (21.2%) | 0.413 | 6 (10%) | 15 (25%) | 0.031 |
| Anti-TPO median (IU/ml) | 5.4200 | 3.2400 | - | 16.3000 | 19.8000 | - | 11.4500 | 17.4000 | - |
Discussion
Results showed a higher rate of anti-TPO antibodies in PCOS patients than in controls. Other studies also claimed a significant relationship between PCOS and Autoimmune thyroiditis disease (AITD). studies in the Slovak Republic (18.75% vs. 7.35% P=0.045) (12), Turkey (37.9% vs. 11.1% p <0.001) (13) and Isfahan, Iran, (30.6% vs. 27.8% P = 0.730) reported a higher prevalence of anti-TPO Abs in PCOS women compared to the control group (14). Although the mechanisms of this association are not clear but probable justifications were offered. Evidences showed excess in estrogens secretion in women leads to higher prevalence of systemic autoimmune disorders (15). The expression of interleukin-6 increases due to over-secretion of estrogens; this process reduces the level of progesterone and its inhibitory effect on immune system in patients with PCOS (16). The result of the immune system over-stimulation could be the inappropriate production of autoantibodies (17,18).
The prevalence of anti-TPO Abs in CD patients was not significantly different from controls in our study. Whereas other studies reported a significant correlation between CD and thyroid autoimmunity. An Italian study in 2001, showed a high prevalence of anti-TPO Abs in CD patients compared to the control group (16.2% vs. 3.8% p<0.0005) (19). In another study by Baharvand et al. in 2020, rate of positive anti-TPO Abs was 4-fold higher in cases than in controls (1.7% vs. 0.4% p=0.03) (20).
The positive anti-TPO Abs level was found in 10% of hepatitis C patients (before interferon therapy). However, controls showed a higher rate of anti-TPO Abs. Previous studies reported contradictory findings. Some researchers including Acay et al. (21) and Hasan Mohammed et al. (22) did not find an association between hepatitis C infection and anti-TPO positive Abs. Whereas other studies like studies in Pakistan (23) and China (24) reported that patients with chronic hepatitis C have a high-risk of AITD.
A notable result in this study was the high level of anti-TPO Abs in both case and control groups. Other studies from other parts of the world like a screening studies in Spain (weman:9.4%;men:2.4%) (25), a study in berlin (3.4%) (26), an African screening study(0%) (27), and A cross-sectional study in Malaysia (12.2%) (28), reported a significantly lower prevalence of anti-TPO Abs in the gener
al population than ours. This high prevalence of anti-TPO Abs in the general population was seen in previous studies in Iran. A studies in Shiraz (22.7%) (29) and Tehran (25.2%) (30) demonstrate a significantly high level of anti-TPO Abs in the control group also a population-based cohort study in Isfahan reported a considerable rate of thyroid dysfunction (23.4%) (7).
A high level of Anti TPO Abs has been thought to arise from a complex combination of genetic, environmental, and endogenous factors (31). In our region, this high level of anti-TPO Abs could be due to racial and regional differences (32), and iodine consumption (33). Golestan province composes of different ethnicities (32), so this may play a role in these results. Some studies demonstrated an association between genetic variations of TPO gene and anti-TPO Abs level. A study in Iran (2017) demonstrate A2173C polymorphism of TPO gene increases the rate of anti-TPO Abs level (P=0.035) (34) also another study in India found other TPO gene polymorphisms (Thr725Pro and Asp666Asp) associated with hypothyroidism (p = 0.01) (35). Therefore, due to the association of TPO gene variations with racial differences, evaluation of TPO gene polymorphisms in our region could shed more light on this issue.
Another reason for the higher rate of anti-TPO Abs in our region could be the iodine sufficient area by consumption of iodine salt (36,37). Iodine sufficiency is related to the increase of thyroid autoimmunity in iodine-sufficient areas (26). Some studies have mentioned excess iodine ingestion as a predisposing factor for thyroid dysfunctions. Studies from areas with high dietary iodine intake in Africa (38) and Japan (39) reported an increase in anti-TPO Abs. Therefore, iodine consumption is better to be done under close control of the health care system and nutritional habits of people such as consumption of salt (38,39).
In conclusion, we found a significant relationship between PCOS and a high level of anti-TPO Abs, but there was not in CD and hepatitis C. In addition, a high level of anti-TPO Abs was seen in the general population. Considering the high prevalence of anti-TPO Abs in this area, and the fact that it could be a strong predictive marker for future thyroid autoimmunity, it may be suggested that the Golestan health system take screening program more seriously. Further studies need to be conducted in order to identify etiologies and underlying reasons of this data in Golestan province.
Acknowledgments
Part of this project was extracted from a thesis dedicated to achieve Doctor of Medicine (M.D.) degree from Golestan University of Medical Sciences (GOUMS). Authors tend to thank research deputy of GOUMS for their supports.
Funding:
Golestan University of Medical Sciences financially supported the present study.
Conflicts of Interest:
The authors declare there is no conflict of interests.
Authors’ contribution:
Study concept and design: BK, MM, TA; Acquisition of data: HH, FH, FA, MM; Analysis and interpretation of data: HH, FH. ; Drafting of the manuscript: HH.FH, MM; Critical revision of the manuscript for important intellectual content: FA, SB; Statistical analysis: HH, FH; Administrative, technical, and material support: BK, TA, SB; Study supervision: HH, FH and FA
References
- 1.McLeod DSA, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine. 2012;42:252–65. doi: 10.1007/s12020-012-9703-2. [DOI] [PubMed] [Google Scholar]
- 2.Leslie D, Lipsky P, Louis Notkins A. Autoantibodies as predictors of disease. J Clin Invest. 2001;108:1417–22. doi: 10.1172/JCI14452. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Hollowell JG, Staehling NW, Dana Flanders W, et al. Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III) J Clin Endocrinol Metab. 2002;87:489–99. doi: 10.1210/jcem.87.2.8182. [DOI] [PubMed] [Google Scholar]
- 4.Siriwardhane T, Krishna K, Ranganathan V, et al. Significance of Anti-TPO as an early predictive marker in thyroid disease. Autoimmune Dis. 2019;2019:1684074. doi: 10.1155/2019/1684074. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Zakeri Z, Sandooghi M. Thyroid disorder in systemic lupus erythematosus patients in Southeast Iran. Shiraz E Med J. 2010;11:34–8. [Google Scholar]
- 6.Moradi S, Ghafarpoor G. Thyroid dysfunction and thyroid antibodies in Iranian patients with vitiligo. Indian J Dermatol. 2008;53:9–11. doi: 10.4103/0019-5154.39733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Aminorroaya A, Meamar R, Amini M, et al. Incidence of thyroid dysfunction in an Iranian adult population: The predictor role of thyroid autoantibodies: Results from a prospective population-based cohort study. Eur J Med Res. 2017;22:21. doi: 10.1186/s40001-017-0260-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Sharifi F, Ghasemi L, Mousavinasab N. Thyroid function and anti-thyroid antibodies in Iranian patients with type 1 diabetes mellitus: Influences of age and sex. Iran J Allergy Asthma Immunol. 2008;7:31–6. [PubMed] [Google Scholar]
- 9.Dewailly D. Diagnostic criteria for PCOS: Is there a need for a rethink? Best Pract Res Clin Obstet Gynaecol. 2016;37:5–11. doi: 10.1016/j.bpobgyn.2016.03.009. [DOI] [PubMed] [Google Scholar]
- 10.Dewar DH, Ciclitira PJ. Clinical features and diagnosis of celiac disease. Gastroenterology. 2005;128:S19–24. doi: 10.1053/j.gastro.2005.02.010. [DOI] [PubMed] [Google Scholar]
- 11.Pawlotsky JM, Lonjon I, Hezode C, et al. What strategy should be used for diagnosis of hepatitis C virus infection in clinical laboratories? Hepatology. 1998;27:1700–2. doi: 10.1002/hep.510270632. [DOI] [PubMed] [Google Scholar]
- 12.Petrikova J, Lazurova I, Dravecka I, et al. The prevalence of non organ specific and thyroid autoimmunity in patients with polycystic ovary syndrome. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159:302–6. doi: 10.5507/bp.2014.062. [DOI] [PubMed] [Google Scholar]
- 13.Hepşen S, Karaköse M, Çakal E, et al. The assessment of thyroid autoantibody levels in euthyroid patients with polycystic ovary syndrome. J Turkish Ger Gynecol Assoc. 2018;19:215–19. doi: 10.4274/jtgga.2018.0001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kachuei M, Jafari F, Kachuei A, Keshteli AH. Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Arch Gynecol Obstet. 2012;285:853–6. doi: 10.1007/s00404-011-2040-5. [DOI] [PubMed] [Google Scholar]
- 15.Lahita RG. Gender disparity in systemic lupus erythematosus, thoughts after the 8th international congress on systemic lupus erythematosus, Shanghai, China, 2007. J Clin Rheumatol. 2008;14:185–7. doi: 10.1097/RHU.0b013e3181778ce0. [DOI] [PubMed] [Google Scholar]
- 16.Petríková J, Lazúrová I, Yehuda S. Polycystic ovary syndrome and autoimmunity. Eur J Intern Med. 2010;21:369–71. doi: 10.1016/j.ejim.2010.06.008. [DOI] [PubMed] [Google Scholar]
- 17.Janssen OE, Mehlmauer N, Hahn S, Öffner AH, Gärtner R. High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Eur J Endocrinol. 2004;150:363–9. doi: 10.1530/eje.0.1500363. [DOI] [PubMed] [Google Scholar]
- 18.Hefler-Frischmuth K, Walch K, Huebl W, et al. Serologic markers of autoimmunity in women with polycystic ovary syndrome. Fertil Steril. 2010;93:2291–4. doi: 10.1016/j.fertnstert.2009.01.056. [DOI] [PubMed] [Google Scholar]
- 19.Sategna-Guidetti C, Volta U, Ciacci C, et al. Prevalence of thyroid disorders in untreated adult celiac disease patients and effect of gluten withdrawal: An Italian multicenter study. Am J Gastroenterol. 2001;96:751–7. doi: 10.1111/j.1572-0241.2001.03617.x. [DOI] [PubMed] [Google Scholar]
- 20.Baharvand P, Hormozi M, Aaliehpour A. Comparison of thyroid disease prevalence in patients with celiac disease and controls. Gastroenterol Hepatol Bed Bench. 2020;13:44–9. [PMC free article] [PubMed] [Google Scholar]
- 21.Acay A, Demir K, Asik G, Tunay H, Acarturk G. Assessment of the frequency of autoantibodies in chronic viral hepatitis. Pak J Med Sci. 2015;31:150–4. doi: 10.12669/pjms.311.6053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Mohammed AH. Investigation of thyroid function disturbance in patients infected with hepatitis C virus. J Int Pharm Res. 2018;45:82–8. [Google Scholar]
- 23.Shafiq MI, Gauhar A, Akram M, Elahi S. Thyroid peroxidase antibodies in non-interferon treated hepatitis C patients in Pakistan. Biomed Res Int. 2015;2015:172981. doi: 10.1155/2015/172981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Yang R, Shan Z, Li Y, Fan C, Li C, Teng W. Prevalence of thyroid autoantibodies in hepatitis C and hepatits B infection in China. Intern Med. 2011;50:811–15. doi: 10.2169/internalmedicine.50.4870. [DOI] [PubMed] [Google Scholar]
- 25.Lucas A, Juliá MT, Cantón A, et al. Undiagnosed thyroid dysfunction, thyroid antibodies, and iodine excretion in a Mediterranean population. Endocrine. 2010;38:391–6. doi: 10.1007/s12020-010-9397-2. [DOI] [PubMed] [Google Scholar]
- 26.Kabelitz M, Liesenkötter KP, Stach B, et al. The prevalence of anti-thyroid peroxidase antibodies and autoimmune thyroiditis in children and adolescents in an iodine replete area. Eur J Endocrinol. 2003;148:301–7. doi: 10.1530/eje.0.1480301. [DOI] [PubMed] [Google Scholar]
- 27.Njemini R, Meyers I, Demanet C, et al. The prevalence of autoantibodies in an elderly sub-Saharan African population. Clin Exp Immunol. 2002;127:99–106. doi: 10.1046/j.1365-2249.2002.01713.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Shahar MA, Omar AM, Wahab ABN, Sukor N, Kamaruddin NA. High prevalence of thyroid antibodies in urban population of peninsular Malaysia. Int Med J Malaysia. 2020;19 Available at: https://journals.iium.edu.my/kom/index.php/imjm/article/view/1559. [Google Scholar]
- 29.Rasaei N, Shams M, Kamali-Sarvestani E, Nazarinia MA. The prevalence of thyroid dysfunction in patients with systemic lupus erythematosus. Iran Red Crescent Med J. 2015;17:e17298. doi: 10.5812/ircmj.17298. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Soltanghoraee H, Arefi S, Mohammadzadeh A, et al. Thyroid autoantibodies in euthyroid women with recurrent abortions and infertility. Iran J Reprod Med. 2010;8:153–6. [Google Scholar]
- 31.Unnikrishnan AG, Kalra S, Sahay RK, et al. Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India. Indian J Endocrinol Metab. 2013;17:647–52. doi: 10.4103/2230-8210.113755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Marjani HA, Biramijamal F, Hossein-Nezhad A, et al. Prevalence of esophageal cancer risk factors among Turkmen and non-Turkmen ethnic groups in a high incidence area in Iran. Arch Iran Med. 2010;13:111–5. [PubMed] [Google Scholar]
- 33.Glinoer D. The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab. 2004;18:133–52. doi: 10.1016/j.beem.2004.03.001. [DOI] [PubMed] [Google Scholar]
- 34.Khoshi A, Sirghani A, Ghazisaeedi M, Mahmudabadi AZ, Azimian A. Association between TPO Asn698Thr and Thr725Pro gene polymorphisms and serum anti-TPO levels in Iranian patients with subclinical hypothyroidism. Hormones. 2017;16:75–83. doi: 10.14310/horm.2002.1721. [DOI] [PubMed] [Google Scholar]
- 35.Balmiki N, Bankura B, Guria S, Das TK, Pattanayak AK, Sinha A, et al. Genetic analysis of thyroid peroxidase (TPO) gene in patients whose hypothyroidism was found in adulthood in West Bengal, India. Endocr J. 2014;61:289–96. doi: 10.1507/endocrj.ej13-0237. [DOI] [PubMed] [Google Scholar]
- 36.Azizi F, Mehran L, Sheikholeslam R, et al. Sustainability of a well-monitored salt iodization program in Iran: Marked reduction in goiter prevalence and eventual normalization of urinary iodine concentrations without alteration in iodine content of salt. J Endocrinol Invest. 2008;31:422–31. doi: 10.1007/BF03346386. [DOI] [PubMed] [Google Scholar]
- 37.Marjani A, Kabir MJ. Incidence of thyroid cancer in Golestan province of Iran: Some initial observations. Pakistan J Med Sci. 2008;24:887–90. [Google Scholar]
- 38.Pearce EN, Gerber AR, Gootnick DB, et al. Effects of chronic iodine excess in a cohort of long-term American workers in West Africa. J Clin Endocrinol Metab. 2002;87:5499–502. doi: 10.1210/jc.2002-020692. [DOI] [PubMed] [Google Scholar]
- 39.Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab. 1994;78:393–7. doi: 10.1210/jcem.78.2.8106628. [DOI] [PubMed] [Google Scholar]