Systemic lupus erythematosus (SLE) represents one of the most complex and challenging autoimmune diseases encountered in clinical practice. This multisystem connective tissue disorder affects approximately 0.1% of the global population, with a pronounced female predominance, particularly impacting women of reproductive age[1]. The disease is characterized by periods of exacerbation and remission, leading to progressive organ damage and significant morbidity if inadequately managed [2]. The clinical manifestations of SLE are diverse, encompassing dermatological, musculoskeletal, renal, cardiovascular, pulmonary, and neurological involvement, making it a prototypical systemic autoimmune condition [3].

The pathophysiology of SLE involves a complex interplay of genetic susceptibility, environmental triggers, and immune system dysregulation. The hallmark of the disease is the production of autoantibodies directed against nuclear antigens, particularly anti-double-stranded DNA and anti-Smith antibodies, which form immune complexes that deposit in various tissues, triggering inflammatory cascades and subsequent organ damage [4]. The chronic inflammatory state in SLE is perpetuated by dysregulated cytokine networks, including elevated levels of type I interferons, interleukin-6, and B-cell activating factor (BAFF), which contribute to both disease progression and the development of comorbid conditions [5].

Among the numerous comorbidities associated with SLE, thyroid dysfunction has emerged as a significant and increasingly recognized clinical concern. The relationship between SLE and thyroid disorders extends beyond mere coincidental occurrence, suggesting shared pathophysiological mechanisms that warrant comprehensive investigation. Epidemiological studies have consistently demonstrated that patients with SLE have a substantially higher prevalence of thyroid dysfunction compared to the general population, with hypothyroidism being the most frequently observed abnormality [6,7]. The prevalence of primary hypothyroidism in SLE patients ranges from 15% to 19%, significantly exceeding the 4.6% prevalence observed in the general population [1]. Furthermore, subclinical hypothyroidism occurs in approximately 9-11% of SLE patients, representing an additional burden of thyroid-related morbidity [2,8].

The autoimmune basis of both SLE and thyroid disease provides compelling evidence for their interconnected pathogenesis. Autoimmune thyroid diseases, including Hashimoto's thyroiditis and Graves' disease, share several immunological features with SLE, including the presence of organ-specific autoantibodies and chronic inflammatory infiltration [9]. Anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies are found in 20-45% of SLE patients, compared to only 10% in the general population [1]. Notably, the specificity of anti-TPO antibodies in SLE patients differs from those found in primary thyroid disorders, suggesting distinct immunological mechanisms [10].

The genetic underpinnings of the SLE-thyroid association have been increasingly elucidated through molecular studies. Patients carrying the R620W polymorphism in the PTPN22 gene, which encodes a T-cell protein tyrosine phosphatase, demonstrate increased susceptibility to developing concurrent SLE and thyroid disease . Additionally, linkage studies have identified a shared susceptibility locus on chromosome 5 (5q14.3-15) for both SLE and autoimmune thyroid disease, providing further evidence for common genetic pathways [1].

The clinical implications of thyroid dysfunction in SLE extend beyond the mere presence of comorbid conditions. Emerging evidence suggests that thyroid abnormalities may significantly influence SLE disease activity, progression, and treatment outcomes. Studies have demonstrated that SLE patients with hypothyroidism exhibit more pronounced disease manifestations and an elevated risk of organ damage [9]. The correlation between thyroid function and SLE severity appears to be particularly evident in patients with lupus nephritis, where thyroid dysfunction is associated with more severe renal involvement and poorer prognosis [11,12].

The relationship between thyroid function and SLE disease activity is bidirectional and complex. Patients with active SLE demonstrate a higher prevalence of thyroid dysfunction, particularly hypothyroidism and elevated anti-thyroid antibodies [13]. The mean SLE Disease Activity Index (SLEDAI) scores are significantly higher in patients with thyroid dysfunction compared to euthyroid patients, suggesting that thyroid abnormalities may serve as both a consequence and a contributor to disease severity [12]. Furthermore, the presence of subclinical hypothyroidism has been shown to delay clinical remission in SLE patients, emphasizing the importance of early detection and treatment [1].

The pathophysiological mechanisms underlying the thyroid-SLE interaction involve multiple interconnected pathways. The chronic inflammatory state characteristic of SLE, mediated by pro-inflammatory cytokines such as interferon-α, interferon-γ, and interleukin-6, can directly impact thyroid function through various mechanisms [14,15]. These cytokines can inhibit thyroid hormone synthesis, reduce peripheral conversion of thyroxine (T4) to triiodothyronine (T3), and promote the development of euthyroid sick syndrome in severely ill patients [16]. Additionally, the autoimmune environment in SLE may trigger cross-reactive immune responses against thyroid antigens, leading to the development of autoimmune thyroid disease [17].

The clinical recognition of thyroid dysfunction in SLE patients is often challenging due to overlapping symptomatology. Many clinical features of hypothyroidism, including fatigue, cognitive impairment, depression, and arthralgia, are also common manifestations of active SLE [18]. This clinical overlap can lead to delayed diagnosis and inadequate treatment of thyroid abnormalities, potentially exacerbating both conditions. Consequently, systematic thyroid function screening has been advocated for all SLE patients, particularly given the high prevalence of thyroid dysfunction and its potential impact on disease outcomes [2,11].

The therapeutic implications of thyroid dysfunction in SLE are multifaceted. Prompt recognition and treatment of thyroid abnormalities may not only improve thyroid-related symptoms but also potentially influence SLE disease activity and progression. Studies have suggested that treatment of subclinical hypothyroidism in SLE patients may accelerate achievement of disease remission, highlighting the importance of a comprehensive endocrine evaluation in lupus management [1]. Furthermore, the presence of thyroid dysfunction may influence the choice and dosing of immunosuppressive medications, requiring careful coordination between rheumatologists and endocrinologists.

Despite the growing recognition of the thyroid-SLE relationship, several important questions remain unanswered. The temporal relationship between thyroid dysfunction and SLE disease activity requires further clarification, as does the impact of thyroid treatment on lupus outcomes. The role of thyroid function as a prognostic biomarker for SLE progression and the optimal screening strategies for thyroid dysfunction in lupus patients are areas that warrant additional investigation.

Given the significant clinical implications of thyroid dysfunction in SLE and the current gaps in understanding, there is a compelling need for well-designed prospective observational studies to comprehensively evaluate the relationship between thyroid function and SLE disease progression and severity. Such studies would provide valuable insights into the natural history of thyroid dysfunction in SLE, identify predictive factors for thyroid abnormalities, and potentially inform evidence-based guidelines for thyroid monitoring and management in lupus patients. This prospective observational study aims to address these critical knowledge gaps by systematically evaluating the relationship between thyroid function parameters and SLE disease activity, progression, and clinical outcomes over time.

Study Type

This study was conducted as a prospective observational study to evaluate the relationship between systemic lupus erythematosus (SLE) and thyroid function abnormalities.

Materials Used

The following materials were used for the study:

• Patient Demographics: Data on age, sex, and clinical history of participants.
• Clinical Data: Information on clinical symptoms and severity of disease at presentation.
• Laboratory Investigations: The following investigations were required for analysis:
• Complete Blood Count (CBC)
• Thyroid Profile (T3, T4, TSH)
• Antinuclear Antibody (ANA) Profile
• Urine Routine Microscopic Examination (Urine RM)
• Liver Function Test (LFT)
• Renal Function Test (RFT)

Methodology

The study was conducted on all newly diagnosed patients of Systemic Lupus Erythematosus (SLE) attending the Rheumatology OPD at M.Y.H. Hospital, Indore, during a 6-month period. The patients included in the study met the established inclusion and exclusion criteria, and data were collected regarding their general and clinical profile, age, sex, clinical symptoms, and disease severity using the SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score.

The following steps were followed:

1. Diagnosis of SLE: Diagnosis was made using the SLICC Criteria.
2. Disease Severity Assessment: Disease severity was assessed through a questionnaire filled by patients at the time of the first consultation and followed up at 3 and 6 months. The SLEDAI score was calculated at each follow-up.
3. Blood Investigations: Routine investigations including thyroid function tests (T3, T4, TSH) were performed at baseline and repeated at the 3-month and 6-month follow-ups.
4. Questionnaire: The questionnaire was filled based on yes/no questions, with no cross-questioning conducted during patient interviews.

Inclusion Criteria

• Newly diagnosed cases of SLE.
• Patients aged 18 to 60 years.

Exclusion Criteria

• Patients who did not consent to participate in the study.
• Prisoners.
• Psychiatric patients.
• Patients on medications affecting thyroid function (e.g., Lithium, TCAs, SSRIs, Steroids, Amiodarone).

Study Duration and Location

• Study Period: The study was conducted over a 6-month period, starting from the approval date of the ethical committee.
• Place of Study: Department of Medicine, MGM Medical College and M.Y.H. Hospital, Indore.

Sample Size

The sample size was calculated using the G*Power software (version 3.1.9.2), and the minimum required sample size was found to be 50, with a 95% confidence interval. The final sample size for the study was 52 patients.

SLEDAI Score

The SLEDAI score was used to assess disease activity, providing a quantitative measure of the severity of lupus disease activity.

Ethical Considerations

This study adhered strictly to established treatment protocols and ethical guidelines. There were no experimental drugs or novel treatment regimens used. Informed consent was obtained from all participants, and patient confidentiality was maintained throughout the process. The study was reviewed and approved by the Institutional Ethics Committee before initiation.

Statistical Analysis Plan

The data were entered into Microsoft Excel and analyzed using SPSS software. Continuous data were expressed as mean ± standard deviation (SD), and categorical data were expressed as proportions and percentages. Appropriate statistical tests, such as ANOVA, were applied where necessary, and the normality of variables was checked using the Shapiro-Wilk test. A p-value of <0.05 was considered statistically significant.

Table 1: Distribution of Study Participants by Age Group

This table presents the age distribution of the study participants. The majority of participants were in the 18-25 years age group, accounting for 40.4% of the total sample. The next largest group was the 31-35 years age group, comprising 28.8%. Fewer participants were in the 26-30 years (21.2%) and 36-40 years (9.6%) age groups, with the total number of participants being 52. This suggests that most patients in this study were relatively young.

Table 2: Gender Distribution of Study Participants

The gender distribution reveals a predominantly female cohort, with 94.2% of participants being female and only 5.8% male. This is reflective of the higher prevalence of Systemic Lupus Erythematosus (SLE) in women compared to men. The total number of participants in the study was 52, indicating a clear gender imbalance, with a significantly higher representation of females.

Table 3: Thyroid Function Status in Systemic Lupus Erythematosus Patients

This table shows the thyroid function status of SLE patients. Most participants (76.9%) were euthyroid, meaning they had normal thyroid function. A smaller proportion (7.7%) had subclinical hypothyroidism, and 15.4% had overt hypothyroidism. This distribution suggests that while most SLE patients in the study had normal thyroid function, thyroid abnormalities were also observed in a significant portion of the population.

Table 4: Disease Severity Based on Clinical Manifestations in Systemic Lupus Erythematosus Patients

Table 4 details the severity of the disease in the study participants. A majority of patients (38.5%) had mild disease severity, followed by moderate severity (34.6%), and severe disease (26.9%). These results indicate that a large proportion of the patients experienced mild to moderate manifestations of SLE, with a smaller group experiencing severe symptoms.

Table 5: Correlation Between Thyroid Function and Disease Severity in SLE

This table examines the relationship between thyroid function and disease severity in SLE patients. Most euthyroid patients were in the mild (18) or moderate (15) severity categories, with fewer (7) in the severe category. Among patients with subclinical hypothyroidism and overt hypothyroidism, a higher proportion were in the severe disease category (6 out of 8 with hypothyroidism). This suggests that thyroid dysfunction, particularly hypothyroidism, may be associated with more severe disease manifestations in SLE patients

The demographic characteristics of the study participants, particularly focusing on the age and gender distribution, demonstrate a clear pattern consistent with the known epidemiology of Systemic Lupus Erythematosus (SLE). The majority of participants were young women, which aligns with the established understanding that SLE predominantly affects females, with a female-to-male ratio of approximately 9:1, particularly in the reproductive age group [19]. This demographic composition is crucial for understanding the relevance of thyroid dysfunction in this population, as both SLE and autoimmune thyroid diseases show similar predilections for affecting women during their childbearing years [20,21].

Thyroid Function Profile in SLE Patients

The findings related to thyroid function reveal important insights into the complex relationship between SLE and thyroid dysfunction. The majority of participants in this study were euthyroid, which is consistent with findings from multiple international studies that demonstrate thyroid dysfunction is not ubiquitous in SLE patients [22,23]. However, the presence of subclinical hypothyroidism and overt hypothyroidism in a notable proportion of participants suggests that thyroid abnormalities may play a significant role in the clinical course of SLE.

Comparing with other studies, the prevalence of thyroid dysfunction shows considerable variation across different populations. A study by Srivastava et al. reported thyroid dysfunction in 31.6% of SLE patients, with primary hypothyroidism being the most common abnormality at 14.5%, followed by subclinical hypothyroidism in 9.2% of subjects [19]. Similarly, Shobha et al. found remarkably high rates of thyroid dysfunction in Indian SLE patients, with clinical hypothyroidism observed in 60% and subclinical hypothyroidism in 24% of patients [20]. In contrast, studies from other populations have reported more conservative estimates, such as Hassan et al., who found hypothyroidism in 11.6% of SLE patients compared to 1.9% in controls [22].

The mechanisms by which thyroid dysfunction, particularly hypothyroidism, could influence disease progression involve multiple interconnected pathways. Thyroid hormones have profound effects on immune function and inflammation, with hypothyroidism potentially exacerbating the chronic inflammatory state characteristic of SLE[24]. Studies have demonstrated that thyroid hormones regulate cytokine production, with T3 and T4 deficiency leading to altered immune responses and increased susceptibility to autoimmune processes [25].

Disease Severity and Thyroid Function Correlation

The correlation between disease severity and thyroid dysfunction represents one of the most significant findings in contemporary SLE-thyroid research. Multiple studies have consistently demonstrated that patients with higher SLE disease activity scores have increased prevalence of thyroid abnormalities. A recent comprehensive study by Li et al. found that SLE patients with hypothyroidism exhibit more pronounced disease manifestations and an elevated risk of organ damage, with FT3 and FT4 levels negatively correlating with SLEDAI-2K scores and 24-hour urinary protein [24].

The study by Srivastava et al. reported a significant mean difference between SLEDAI scores in the thyroid dysfunction group (11.3) compared to the euthyroid group (4.5), with a p-value of 0.001, indicating a strong association between disease severity and thyroid dysfunction [19]. This finding is corroborated by Garcia-Carrasco et al., who demonstrated that subclinical hypothyroidism was more prevalent in patients with lupus activity compared to those without (18.0% vs 0%; p = 0.001) [26].

The potential explanations for this correlation include immune dysregulation, metabolic effects, and thyroid hormone's role in inflammation. The autoimmune environment in SLE may trigger cross-reactive immune responses against thyroid antigens, leading to the development of autoimmune thyroid disease [27]]. Additionally, the chronic inflammatory state mediated by pro-inflammatory cytokines such as interferon-α, interferon-γ, and interleukin-6 can directly impact thyroid function through inhibition of thyroid hormone synthesis and promotion of euthyroid sick syndrome [28].

Thyroid Autoantibodies and Lupus Nephritis

Studies examining the relationship between lupus nephritis and thyroid dysfunction have revealed particularly compelling associations. Fotoh et al. demonstrated that SLE patients with lupus nephritis had significantly higher thyroid autoantibodies (anti-thyroglobulin and thyroid peroxidase) than SLE patients without nephritis (90% vs 55%, 60% vs 30%, and 65% vs 30%, respectively) [27]. This finding suggests that renal involvement in SLE may be associated with more pronounced autoimmune thyroid disease.

The work by Li et al. further supports this association, showing that SLE patients with renal involvement exhibited lower levels of FT3 and FT4 compared to those without renal involvement, along with elevated TSH levels [24]. These findings indicate that thyroid dysfunction may serve as both a consequence and a contributor to disease severity, particularly in patients with lupus nephritis.

The prevalence of anti-thyroid antibodies in SLE patients varies significantly across different populations and studies. While some studies report anti-TPO antibodies in 20-45% of SLE patients compared to 10% in the general population [29], others have found more conservative estimates. The study by Srivastava et al. found anti-TPO antibodies in 35.5% of SLE patients, with thyroid dysfunction present in 48.1% of these seropositive subjects [19].

International studies have provided varying results regarding the strength of association between thyroid disorders and disease severity. A study from Iran by Khajehei et al. found thyroid dysfunction in 24.1% of SLE patients compared to 13.3% of controls, with elevated TSH being the most common abnormality [30]. However, some studies, such as the one by Al-Homood et al., did not find a significant association between thyroid dysfunction and SLE disease activity, suggesting that hypothyroidism can occur independently of SLE exacerbations [31].

The discrepancies in research findings can be attributed to several factors including variations in study design, sample size, population characteristics, and diagnostic criteria for thyroid dysfunction. Cross-sectional studies may not capture the temporal relationship between thyroid dysfunction and SLE activity, while longitudinal studies provide better insights into causality.

The relationship between thyroid dysfunction and SLE represents a complex interplay of autoimmune, genetic, and inflammatory mechanisms. Current evidence demonstrates a clear association between thyroid abnormalities and increased SLE disease severity, particularly in patients with lupus nephritis. While study findings show some variation across different populations, the consistent pattern of increased thyroid dysfunction prevalence in SLE patients compared to healthy controls supports the need for routine thyroid screening as part of comprehensive SLE management. Future research should focus on longitudinal studies to establish causality and investigate whether thyroid hormone replacement therapy can serve as an adjunctive treatment to improve SLE outcomes.

1. Miller FW, Pollard KM, Parks CG, Germolec DR, Leung PS, Selmi C, et al. Criteria for environmentally associated autoimmune diseases. J Autoimmun. 2012;39(4):253-8.
2. Antonelli A, Fallahi P, Elia G, Ragusa F, Paparo SR, Ruffilli I, et al. Thyroid Disease and Systemic Lupus Erythematosus. Medicina (Kaunas). 2023;59(11):1911.
3. Tsokos GC. Systemic lupus erythematosus. N Engl J Med. 2011;365(22):2110-21.
4. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358(9):929-39.
5. Postal M, Appenzeller S. The importance of cytokines and autoantibodies in depression in systemic lupus erythematosus. Autoimmun Rev. 2015;14(1):30-35.
6. Goh KL, Wang F. Thyroid disorders in patients with systemic lupus erythematosus. Ann Rheum Dis. 1986;45(7):579-83.
7. Boelaert K, Newby PR, Simmonds MJ, Holder RL, Carr-Smith JD, Heward JM, et al. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am J Med. 2010;123(2):183.e1-9.
8. Shobha V, Mahendranath KM, Suryanarayana BS, Suresh T, Kumar SA, Ramesh V, et al. Prevalence of Thyroid Dysfunction in Patients with Systemic Lupus Erythematosus. Indian J Rheumatol. 2020;15(2):79-83.
9. Li Q, Yu X, Zhao W, Li L, Zhao Y, Wang G. Thyroid hormones in systemic lupus erythematosus: The catalyst for disease progression. Autoimmun Rev. 2025;24(2):103463.
10. Weetman AP, Walport MJ. The association of autoimmune thyroiditis with systemic lupus erythematosus. Br J Rheumatol. 1987;26(5):359-61.
11. Magaro M, Zoli A, Altomonte L, Mirone L, La Sala L, Barini A, et al. The association of silent thyroiditis with active systemic lupus erythematosus. Clin Exp Rheumatol. 1992;10(1):67-70.
12. Hassan AB, Badr Eldin EM. Thyroid dysfunction in patients with systemic lupus erythematosus and rheumatoid arthritis. Egypt J Immunol. 2007;14(2):83-90.
13. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Ghinoi A, Rotondi M, et al. Thyroid disorders in chronic hepatitis C virus infection. Thyroid. 2006;16(6):563-72.
14. Fotoh DS, Abass DS, Galbat EA. Thyroid dysfunction in patients with lupus nephritis: relation to disease activity and progression. Menoufia Med J. 2022;35(3):1095-101.
15. Srivastava P, Abhinav G, Mishra K, Krishnani N, Haque M, Aggarwal A. Thyroid Dysfunction In Systemic Lupus Erythematosus And Its Correlation With Disease Activity. Int J Med Sci Clin Res. 2023;6(4):626-31.
16. Boumpas DT, Austin HA III, Fessler BJ, Balow JE, Klippel JH, Lockshin MD. Systemic lupus erythematosus: emerging concepts. Part 1: Renal, neuropsychiatric, cardiovascular, pulmonary, and hematologic disease. Ann Intern Med. 1995;122(12):940-50.
17. Garcia-Carrasco M, Mendoza-Pinto C, Zamora-Ustaran A, Garcia de la Torre P, Sandoval-Cruz H, Escobar-Linares LE, et al. Thyroid disorders, hyperprolactinemia and systemic lupus erythematosus activity. Int J Clin Rheumatol. 2014;9(5):441-50.
18. Shobha V, Mahendranath KM, Suryanarayana BS, Suresh T, Kumar SA, Ramesh V, et al. Prevalence of Thyroid Dysfunction in Patients with Systemic Lupus Erythematosus. Indian J Rheumatol. 2020;15(2):79-83.
19. Abira M, Akhter QS, Islam MS, Islam S, Khan IS, Akter F, et al. Thyroid Dysfunction and Its Association with Systemic Lupus Erythematosus. J Mym Med Coll Women Health. 2017;6(2):35-40.
20. Shobha V, Mahendranath KM, Suryanarayana BS, Suresh T, Kumar SA, Ramesh V, et al. Prevalence of Thyroid Dysfunction in Patients with Systemic Lupus Erythematosus. Indian J Rheumatol. 2020;15(2):79-83.
21. Klionsky Y, Antonelli M. Thyroid Disease in Lupus: An Updated Review. Open Access Rheumatol. 2020;12:13-27.
22. Hassan AB, Badr Eldin EM. Thyroid dysfunction in patients with systemic lupus erythematosus and rheumatoid arthritis. Egypt J Immunol. 2007;14(2):83-90.
23. Antonelli A, Ferri C, Fallahi P, Ferrari SM, Sebastiani M, Palazzo D, et al. Systemic Lupus Erythematosus and Thyroid Autoimmunity. Front Endocrinol (Lausanne). 2017;8:138.
24. Li Q, Yu X, Zhao W, Li L, Zhao Y, Wang G. Thyroid hormones in systemic lupus erythematosus: The catalyst for disease progression. Autoimmun Rev. 2025;24(2):103463.
25. Antonelli A, Fallahi P, Elia G, Ragusa F, Paparo SR, Ruffilli I, et al. Thyroid Disease and Systemic Lupus Erythematosus. Medicina (Kaunas). 2023;59(11):1911.
26. Garcia-Carrasco M, Mendoza-Pinto C, Zamora-Ustaran A, Garcia de la Torre P, Sandoval-Cruz H, Escobar-Linares LE, et al. Thyroid disorders, hyperprolactinemia and systemic lupus erythematosus activity. Int J Clin Rheumatol. 2014;9(5):441-50.
27. Fotoh DS, Abass DS, Galbat EA. Thyroid dysfunction in patients with lupus nephritis: relation to disease activity and progression. Menoufia Med J. 2022;35(3):1095-101.
28. Fliers E, Bianco AC, Langouche L, Boelen A. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol. 2015;3(10):816-25.
29. Kohno Y, Yamaguchi F, Saito K, Niimi H, Nishikawa T, Hosoya T. Anti-thyroid peroxidase antibody activity in sera of patients with systemic lupus erythematosus. Clin Exp Immunol. 1991;83(3):507-11.
30. Khajehei S, Sobhani K, Foroughi F, Azizkhani I, Ramezani M. Thyroid Disorder in Systemic Lupus Erythematosus Patients in Southeast of Iran. Shiraz E Med J. 2010;11(3):146-51.
31. AL-Homood IA, Abdulkareem AA, Al-Ballaa SR, Al-Arem AM, Almehza W, ALNasser S, et al. Prevalence of Thyroid Dysfunction in Patients with Systemic Lupus Erythematosus: A Single-Center Study. Curr Rheumatol Rev. 2018;14(1):80-4.