|Year : 2020 | Volume
| Issue : 2 | Page : 79-83
Prevalence of thyroid dysfunction in patients with systemic lupus erythematosus: A descriptive cross sectional study
Anasuya S Desai1, Sara Chandy1, Shine J Pakalomattom1, Vineeta Shobha2
1 Department of General Medicine, St. Johns Medical College Hospital, Bengaluru, Karnataka, India
2 Department of Clinical Immunology and Rheumatology, St. Johns Medical College Hospital, Bengaluru, Karnataka, India
|Date of Web Publication||29-May-2020|
Dr. Vineeta Shobha
Department of Clinical Immunology and Rheumatology, St. Johns Medical College Hospital, Bengaluru - 560 034, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Estimate of prevalence of thyroid dysfunction in systemic lupus erythematosus (SLE) patients from India is scarce. The present study evaluated the prevalence of thyroid dysfunction and anti-thyroid peroxidase (TPO) antibodies in SLE patients, and the most prominent clinical features of thyroid dysfunction were noted.
Materials and Methods: This descriptive, cross-sectional study involved 100 adult patients diagnosed with SLE at a tertiary teaching hospital, Bengaluru, India. The study excluded patients on medications that are known to cause thyroid dysfunctions, those with a history of thyroidectomy, and those with other systemic autoimmune diseases.
Results: Among the 100 recruited patients, 99 were females, and most (47%) belonged to the age group of 20–30 years, the median duration of lupus was 24 months. Thyroid dysfunction was observed in 42% (n = 42), and hypothyroidism was the most common thyroid abnormality. None of the patients had hyperthyroidism. Among the patients with thyroid dysfunction, the corresponding number of patients with clinical hypothyroidism and subclinical hypothyroidism were 71% (n = 30) and 29% (n = 12). Of 25 patients with elevated anti-TPO, 48% (n = 12) had clinical hypothyroidism, 20% (n = 5) had subclinical hypothyroidism, and 32% (n = 8) had normal thyroid-stimulating hormone and free T4. Most of the patients with thyroid dysfunction were newly diagnosed, and the predominant symptoms noted were fatigue (75%), hair loss (75%), and joint pain (63%).
Conclusions: The prevalence of thyroid dysfunction was found to be higher in SLE than previously published cohorts in India and the rest of the world. It does not affect lupus activity.
Keywords: Anti-thyroid peroxidase, clinical hypothyroidism, hyperthyroidism, subclinical hypothyroidism, systemic lupus erythematosus, thyroid dysfunction
|How to cite this article:|
Desai AS, Chandy S, Pakalomattom SJ, Shobha V. Prevalence of thyroid dysfunction in patients with systemic lupus erythematosus: A descriptive cross sectional study. Indian J Rheumatol 2020;15:79-83
|How to cite this URL:|
Desai AS, Chandy S, Pakalomattom SJ, Shobha V. Prevalence of thyroid dysfunction in patients with systemic lupus erythematosus: A descriptive cross sectional study. Indian J Rheumatol [serial online] 2020 [cited 2021 Sep 16];15:79-83. Available from: https://www.indianjrheumatol.com/text.asp?2020/15/2/79/282824
| Introduction|| |
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder affecting women in their reproductive years. Multisystem organ involvement and tissue damage in SLE is mediated by the deregulation of self-reactive B-cells, resulting in autoantibody production, immune complex disposition, and complement activation.
Many studies have demonstrated that autoimmune thyroid diseases marked by the presence of anti-thyroid antibodies are associated with various rheumatological disorders. Goh and Wang in 1986 have reported that thyroid disorders are more prevalent in SLE patients than in general population. In a recent review and meta-analysis, a higher prevalence of hypothyroidism was noted among SLE patients compared with the general population (odds ratio of 2.93; P < 0.05). This included ten studies with 10,500 SLE patients and 44,170 healthy controls. In addition, 5.67-fold increased the risk of subclinical hypothyroidism based on five studies was documented. The relationship between SLE and hyperthyroidism as well as subclinical hyperthyroidism is inconclusive at present.
Although several studies reported increased prevalence of thyroid disease in SLE patients, it has not been established whether the occurrence of SLE functions as an independent risk factor for developing thyroid abnormalities. In addition, it has not been studied whether the association is coincidental, as both diseases are more prevalent among young- and middle-aged women.
Prevalence studies evaluating the prevalence of thyroid dysfunction in Indian SLE patients are very limited. An Indian study by Pillai and Velayudhan, conducted in 100 SLE patients, has reported hypothyroidism (26%) as the common thyroid abnormality noted, followed by subclinical hypothyroidism (24%) and hyperthyroidism (16%). Kumar et al. reported that primary hypothyroidism (14%) and subclinical hypothyroidism (12%) were the most common alterations among lupus patients, which was significantly higher when compared to control group (5% and 3%, respectively). The present study was intended to estimate the prevalence of thyroid abnormalities, anti-thyroid peroxidase (TPO) antibodies, and the most prominent clinical features of thyroid dysfunction in SLE patients attending a tertiary care center in South India.
| Materials and Methods|| |
The descriptive, cross-sectional observational study was conducted at St. John's National Academy of Medical Sciences, which is a tertiary care, multispecialty teaching hospital Bengaluru, India. The study recruited 100 consecutive adult SLE patients fulfilling Systemic Lupus International Collaborating Clinics 2012 lupus classification criteria. Patients receiving medications that are known to cause thyroid dysfunction, and those with a history of thyroidectomy, SLE with pregnancy and subject with systemic autoimmune diseases were excluded from the study. The approval of the institutional ethics committee was obtained before the study.
Complete clinical assessment, with a specific focus on features of hypothyroidism or hyperthyroidism, was conducted for all the enrolled patients and details entered into a prestructured pro forma. SLE Disease Activity Index-2K (SLEDAI-2K) was calculated for all patients. Specific laboratory investigations included the estimation of free T4 (FT4), thyroid-stimulating hormone (TSH), and anti-TPO antibody. Patients were classified as hyperthyroidism (clinical and subclinical), clinical hypothyroidism, subclinical hypothyroidism, and those with elevated anti-TPO alone using standard definitions. Overt hypothyroidism was defined as TSH levels >10 lU/L and subclinical hypothyroidism as elevated TSH (5–10 lU/L) with normal (FT4 10–28 pmol/l) as per the laboratory cutoffs. Five TSH and FT4 were tested using a chemiluminescence enzyme immunoassay. Anti-TPO antibody levels were tested using chemiluminescent microparticle immunoassay. All assays were carried out in the laboratory of the department of clinical biochemistry, which is the National Accreditation Board for Testing and Calibration Laboratories accredited.
Descriptive statistical analysis was conducted to calculate the mean, standard deviation, and percentage, wherever appropriate. The prevalence of different thyroid dysfunctions and anti-TPO status in recruited patients was calculated as proportion or percentage. Chi-square test was used to for comparing different groups. Probability value < 5% was considered as statistically significant. The analysis was performed using SPSS version 18 software (SPSS Inc., USA).
| Results|| |
Of the 100 recruited SLE patients, 99 were women; and majority of the patients (47%) belonged to the age group of 20–30 years. Duration of SLE ranged from newly diagnosed to 14 years, the median duration of lupus being 24 months. The duration of hypothyroidism ranged from newly diagnosed to 19 years [Table 1].
|Table 1: Distribution of the subjects based on the duration of SLE and thyroid dysfunction|
Click here to view
Among the total enrolled patients, 50 patients were found to have thyroid dysfunction. Thyroid dysfunction was detected before the diagnosis of SLE in 24 (48%) of the patients, whereas in 11 (22%), thyroid dysfunction was detected after the SLE diagnosis. Both the diseases were diagnosed simultaneously in 15 (30%) of the patients. The time relation between the onset of SLE and thyroid dysfunction is shown in [Figure 1].
|Figure 1: The time relation between the onset of systemic lupus erythematosus and thyroid dysfunction in recruited patients|
Click here to view
Hypothyroidism was the most common thyroid abnormality noted, and none had hyperthyroidism. Among the patients with thyroid dysfunction, the corresponding number of patients with clinical hypothyroidism and subclinical hypothyroidism were 71% (n = 30) and 29% (n = 12) [Table 2]. Overall, elevated anti-TPO levels were noted in 25 patients. Among them, the prevalence of clinical hypothyroidism, subclinical hypothyroidism, and normal TSH and FT4 were 48% (n = 12), 20% (n = 5), and 32% (n = 8), respectively [Table 3].
Fatigue (75%), hair loss (75%), and joint pain (63%) were the predominant symptoms reported in patients with thyroid dysfunctions. Among all the symptoms, statistical significance was noted for joint pain (P = 0.02) and constipation (P = 0.02). Overall, of 16 patients with neurological manifestations, 11 fulfilled american college of rheumatology (ACR) neurological criteria for neuropsychiatric systemic lupus erythematosus, which included psychosis (n = 6), peripheral neuropathy, and hemiplegia, seizure, and cerebral venous thrombosis one each. Thyroid dysfunction was documented in four of them. Of two patients with Carpal Tunnel syndrome, both had overt hypothyroidism. Serositis was noted in 11 patients in overall cohort, five of them had thyroid dysfunction. Pleural effusion and pericardial effusion were reported in six and two patients, respectively, and three patients had both. Largely, classical manifestations of hypothyroidism such as weight gain, constipation, and delayed tendon jerks were conspicuous by their absence.
Only one patient had hypothyroidism in family. None had a family history of lupus. None of autoantibodies (Immunoblot-EUROIMMUN) correlated with thyroid dysfunction or the presence of anti-TPO.
The mean SLEDAI-2K in the entire cohort was 7.2 (±5.6) with a range from 0 to 26. There was no significant difference in SLEDAI scores between euthyroid and thyroid dysfunction group (P = 0.19).
| Discussion|| |
It is well established that SLE is significantly associated with thyroid dysfunction, specifically hypothyroidism and subclinical hypothyroidism. We explored this association in our cohort of lupus patients.
The mean age of patients enrolled in the present study was 29.4 ± 9.3 years, and most of them belonged to the age group of 20–30 years. In contrast to other studies from India (Kumar et al. and Porkodi et al.), we report an overall higher prevalence of thyroid dysfunction, overt hypothyroidism (30%) and subclinical hypothyroidism (12%) in our cohort. However, none had hyperthyroidism in our cohort. Elsewhere, Khataybeh et al., Kakehasi et al., and Miller et al. have observed subclinical hypothyroidism as the major thyroid abnormality, but to a much lesser extent [Table 4].,,
|Table 4: Comparative data Demographic characteristics, Thyroid Dysfunction and prevalence of anti TPO antibody|
Click here to view
In stark contrast to these findings, the 10-year study by Lin et al. have reported that the rate of thyroid diseases was significantly lesser in SLE patients (8.1% vs. 16.9%; P < 0.001) when compared to non-SLE-matched controls. Several studies have reported inconsistent findings on the association between thyroid autoimmunity and SLE. Most of these individual studies were not powerful enough to determine the association and had relatively small sample size. Recently published systemic meta-analysis aimed at providing reliable estimates of the extent of any association has corroborated the hypothesis, suggesting an increased thyroid autoimmunity risk in SLE patients.
Higher prevalence of thyroid dysfunction noted in the present study could be attributed to higher prevalence of thyroid disorders in Asians than the Western population raising the risk over and above the ethnic predisposition. It could also be attributed to significantly higher female to male ratio of the present study, as hypothyroidism is 4–5 times more common in females than males., In a similar study at our hospital conducted in 100 patients of rheumatoid Arthritis, 15% were detected as overt hypothyroidism, 5% subclinical hypothyroidism, while hyperthyroidism was detected in 1%. In a population-based study done in Cochin, India, the prevalence of hypothyroidism was 3.9% and that of subclinical hypothyroidism was 9.4% in 971 iodine-sufficient adults. The prevalence was higher, at 11.4% in women, when compared with men, in whom the prevalence was 6.2%.
In the current study, 48% of the patients were detected with thyroid dysfunctions before the diagnosis of SLE; whereas in 22% of the patients, the dysfunctions were detected after the detection of SLE. In 30% of the patients, both the diseases were diagnosed simultaneously. Porkodi et al. have demonstrated that thyroid dysfunction preceded SLE in 30%, postdated in 40%, while the concurrent diagnosis was made in 30%. The study by Antonelli et al. has noted the diagnosis of autoimmune disease at SLE onset in 2.9% of patients, and 70.6% of patients developed thyroid disease during follow-up. This might be attributed to high index of suspicion and ease of availability of thyroid assays.
Of the 100 SLE patients, elevated anti-TPO levels were noted in 25 (25%) patients. Among them, 8 (32%) patients had normal thyroid function tests, 12 had clinical hypothyroidism, and 5 had subclinical hypothyroidism. Based on the literature evidence, a review by Blich et al. has concluded on the increased prevalence of anti-TPO antibodies in SLE patients than in the general population. Anti-TPO autoantibodies play a crucial role in the diagnosis of autoimmune thyroid diseases and in estimating the disease course. Kohno et al. have reported that the anti-TPO autoantibody specificities noted in SLE are different from that in thyroid disorders.
The prominent attributable symptoms of thyroid dysfunctions noted in the present study patients were as follows: fatigue (75%), hair loss (75%), and joint pain (63%). These symptoms are frequent in lupus population too and undetected thyroid dysfunction may contribute to persistent symptoms. Goh and Wang also noted a higher incidence of joint pain, mucocutaneous involvement, lymphadenopathy, and renal manifestations in SLE patients with thyroid dysfunction.
Lack of a control group for comparison was one of the major limitations of the study. The skewed enrollment of female patients in the present study is attributed to increased preponderance of SLE in females than males. The study has not matched the clinical and SLE-related antibody profiles with that of the thyroid antibody profile due to the limited sample size, which would have helped in further corroborating the association.
Corroborating this association and thereby, early detection and treatment for both the diseases would be beneficial for planning therapeutic strategies.
| Conclusions|| |
In summary, the present study underscores the need for conducting thyroid function and TPO antibody tests as part of the biochemical and immunological profiling of SLE patients. Moreover, there is a greater possibility of overlooking the diagnosis of thyroid dysfunctions in SLE patients, as both the diseases have similar clinical manifestations. Further studies involving larger population are warranted to substantiate this association.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dan L, Anthony F, Dennis K, Stephen H, J. Larry J, Joseph L. Harrison's Principles of Internal Medicine. 18th
ed. Vol. 1 and 2. McGraw Hill Education USA; 2011.
Pillai SS, Velayudhan G. Thyroid dysfunction in SLE and association of thyroid antibody levels with disease activity in SLE. J Evolution Med Dent Sci 2017;33;2684-8. [doi: 10.14260/ jemds/2017/579].
Pyne D, Isenberg DA. Autoimmune thyroid disease in systemic lupus erythematosus. Ann Rheum Dis 2002;61:70-2.
Goh KL, Wang F. Thyroid disorders in systemic lupus erythematosus. Ann Rheum Dis 1986;45:579-83.
Luo W, Mao P, Zhang L, Yang Z. Association between systemic lupus erythematosus and thyroid dysfunction: A meta-analysis. Lupus 2018;27:2120-8.
Kumar K, Kole AK, Karmakar PS, Ghosh A. The spectrum of thyroid disorders in systemic lupus erythematosus. Rheumatol Int 2012;32:73-8.
Ighe A, Dahlström Ö, Skogh T, Sjöwall C. Application of the 2012 systemic lupus international collaborating clinics classification criteria to patients in a regional swedish systemic lupus erythematosus register. Arthritis Res Ther 2015;17:3.
Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity inde×2000. J Rheumatol 2002;29:288-91.
Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism. Lancet 2017;390:1550-62.
The American college of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes. Arthritis Rheum 1999;42:599-608.
Khataybeh O, Al Mashaleh M, Burgan A, Haddad F, Zgoul N, Hussamia M, et al
. Thyroid Dysfunctions among Jordanian Patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Hospital Based Study. J R Med Serv 2013;20;37-42. [doi: 10.12816/0000050].
Kakehasi AM, Dias VN, Duarter JE, Duarte Lanna CC, Parreiras De Carvalho MA. Thyroid abnormalities in systemic lupus erythematosus: A study in 100 Brazilian patients. Rev Bras Reumatol 2006;46;375-9. [doi: 10.1590/ S0482 50042006000600003].
Miller FW, Moore GF, Weintraub BD, Steinberg AD. Prevalence of thyroid disease and abnormal thyroid function test results in patients with systemic lupus erythematosus. Arthritis Rheum 1987;30:1124-31.
Wen-Ya L, Chia-Li C, Lin-Shien F, Lin CH, Heng-Kuei. (2014). Systemic lupus erythematosus and thyroid disease: A 10-year study. J Microbiol Immunol Infect 2015;48:676-83. [doi: 10.1016/j.jmii.2014.03.004].
Pan XF, Gu JQ, Shan ZY. Patients with systemic lupus erythematosus have higher prevalence of thyroid autoantibodies: A systematic review and meta-analysis. PLoS One 2015;10:e0123291.
Walsh JP, Bremner AP, Feddema P, Leedman PJ, Brown SJ, O'Leary P. Thyrotropin and thyroid antibodies as predictors of hypothyroidism: A 13-year, longitudinal study of a community-based cohort using current immunoassay techniques. J Clin Endocrinol Metab 2010;95:1095-104.
Usha Menon V, Sundaram KR, Unnikrishnan AG, Jayakumar RV, Nair V, Kumar H. High prevalence of undetected thyroid disorders in an iodine sufficient adult south Indian population. J Indian Med Assoc 2009;107:72-7.
Blich M, Rozin A, Edoute Y. Systemic lupus erythematosus and thyroid disease. IMAJ 2004;6:218-20.
Antonelli A, Fallahi P, Mosca M, Ferrari SM, Ruffilli I, Corti A, et al
. Prevalence of thyroid dysfunctions in systemic lupus erythematosus. Metabolism 2010;59:896-900.
Kohno Y, Naito N, Saito K, Hoshioka A, Niimi H, Nakajima H, et al
. Anti-thyroid peroxidase antibody activity in sera of patients with systemic lupus erythematosus. Clin Exp Immunol 1989;75:217-21.
[Table 1], [Table 2], [Table 3], [Table 4]