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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 35  |  Issue : 3  |  Page : 1318-1323

Thyroid dysfunction in patients with lupus nephritis: relation to disease activity and progression


1 Department of Physical Medicine, Rheumatology, and Rehabilitation, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission09-Mar-2022
Date of Decision05-May-2022
Date of Acceptance08-May-2022
Date of Web Publication29-Oct-2022

Correspondence Address:
Eman A Galbat
Al Shohada, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_78_22

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  Abstract 


Objectives
To evaluate thyroid dysfunction prevalence and antithyroid antibody production including antithyroglobulin and thyroid peroxidase in systemic lupus erythematosus (SLE) patients with lupus nephritis and their relationship to SLE disease activity and progression.
Background
SLE is an autoimmune disorder in which the production of a variety of antibodies like anti-double-stranded DNA, antinuclear antibodies, anti-Ro antibodies, and others is associated with the organ-specific autoimmune thyroiditis.
Patients and methods
This cross-sectional study included 120 SLE patients divided into two groups: 60 SLE patients with nephritis and 60 SLE patients without nephritis. Clinical assessment includes assessment of disease activity by SLE disease activity (Systemic Lupus Erythematosus Disease Activity Index). Laboratory assessment of thyroid hormones and antithyroid antibody was done by enzyme-linked immunosorbent assay.
Results
SLE patients with nephritis had significantly higher thyroid autoantibodies (antithyroglobulin and thyroid peroxidase) than SLE patients without nephritis (90 vs. 55%, 60 vs. 30%, and 65 vs. 30%, respectively). However the means of complement 3 and complement 4 were lower in SLE patients with nephritis than SLE patients without nephritis (51.8 ± 17.6 vs. 103.9 ± 24.8 and 8.8 ± 3.6 vs. 35.4 ± 23.5, respectively).
Conclusions
SLE patients with lupus nephritis had significantly higher thyroid autoantibodies than SLE patients without nephritis with significant positive correlations between these autoantibodies and SLE disease activity. Thyroid autoantibodies are important new and potential prognostic factors predicting poor outcomes in SLE patients with lupus nephritis. Further large-scale, multicenter, and prospective studies are needed to confirm these findings.

Keywords: lupus nephritis, systemic lupus erythematosus, thyroid dysfunction


How to cite this article:
Fotoh DS, Abass DS, Galbat EA. Thyroid dysfunction in patients with lupus nephritis: relation to disease activity and progression. Menoufia Med J 2022;35:1318-23

How to cite this URL:
Fotoh DS, Abass DS, Galbat EA. Thyroid dysfunction in patients with lupus nephritis: relation to disease activity and progression. Menoufia Med J [serial online] 2022 [cited 2024 Mar 28];35:1318-23. Available from: http://www.mmj.eg.net/text.asp?2022/35/3/1318/359525




  Introduction Top


The loss of immunological tolerance to self-antigens is the initial cause of autoimmune diseases contributing to a heterogeneous group of disorders with multiple alterations in the immune system causing a group of syndromes targeting specific organs or affecting the body systematically[1],[2],[3].

Systemic lupus erythematosus (SLE) is an autoimmune disorder in which the production of a variety of antibodies like anti-double-stranded DNA, antinuclear antibodies, anti-Ro antibodies, and others is associated with the organ-specific autoimmune thyroiditis (AT)[4],[5]. Several studies have reported the association between thyroid dysfunction and thyroid autoantibody production in SLE patients with lupus nephritis[6]. While some studies reported a higher prevalence of hyperthyroidism in SLE patients, others reported a higher prevalence of hypothyroidism[7].

On the one hand, thyroid hormones play a major role in the early development of kidneys structurally and thereafter in the regulation of major glomerular and tubular functions as well as water and electrolyte balance; on the other hand, the kidneys are important in the metabolism and elimination of thyroid hormones[8]. Thus, the dysfunctioning of either organ is expected to have subsequent dangerous consequences on both of them.

Lupus nephritis is a significant complication of SLE characterized by the presence of proteinuria in which albumin contributes to the major fraction of protein excreted owing to the selective nature of proteinuria, in addition to many other important globulins, hormones, and hormone-binding proteins excreted in a significant amount causing clinical implications other than renal dysfunction itself[9]. Thyroxine and thyroid-binding globulins (TBG) loss in urine is an important concern. In the early stages, the levels of free triiodothyronine and free thyroxine (FT4) remain normal with no metabolic consequences. However, with prolonged excretions of TBG, the thyroid gland starts to overfunction to maintain constant hormone levels causing the reduction in the levels of free thyroid hormones with the elevation of thyroid-stimulating hormone (TSH) levels[10]. The goal of this study was to evaluate thyroid dysfunction prevalence and antithyroid antibodies (ATA) production including antithyroglobulin (ATg) and thyroid peroxidase (TPO) in SLE patients with lupus nephritis and their relationship to SLE disease activity and progression.


  Patients and methods Top


Study design and patient groups

A cross-sectional study included 120 participants, chosen according to the inclusion and exclusion criteria which met the American College of Rheumatology classification criteria of SLE[11],[12]. The patients were recruited from the Rheumatology and Internal Medicine Clinics of Menoufia University Hospital after approval from the Research and Ethics Committee of Faculty of Medicine, Menoufia University from January 2020 to December 2020. Patients were divided into two groups: SLE with nephritis which included 60 patients and SLE without nephritis which also included 60 patients. Their age ranged from 23 to 50 years and the duration of the disease ranged from 1 to 10 years. Females represent 62.5% while males represent 37.5%.

Exclusion criteria

All patients with the previous diagnosis of thyroid dysfunction, other autoimmune diseases, and pregnant women were excluded from the study.

Ethical guidelines

This study was conducted under the Declaration of Helsinki and was accepted by our University Hospital Committee's Institutional Review Board. All participants included in the study signed an informed written consent. Data were collected in a preorganized data sheet (case sheet) by the researcher from patients fulfilling the inclusion and exclusion criteria.

Methods: clinical assessment

SLE activity was evaluated using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)[13].

Thyroid function tests and laboratory assessment

FT4, TSH, ATg antibodies, and anti-TPO antibodies were tested in the serum using enzyme-linked immunosorbent assay. Methods for thyroid hormone assessment include two categories: direct methods, which include a physical separation of the free-from protein-bound hormone, and estimate tests, which either calculate a free hormone index from a measurement of total hormone corrected for binding proteins with either a TBG measurement or a binding-protein estimate, or immunoassays that employ an antibody to sequester a small amount of the total hormone that is purportedly proportional to the free hormone concentration. The normal range for TSH is 0.5–4.5 mU/l and 0.7–1.8 ng/dl for FT4.

Elevation of TSH and suppression of FT4 was defined as clinical hypothyroidism, while the elevation of TSH with a normal FT4 was defined as subclinical hypothyroidism. Treatment with L-thyroxine was considered to be hypothyroid state irrespective of the TSH levels in these conditions. Suppression of TSH levels with normal FT4 levels was considered as subclinical hyperthyroidism while suppression of TSH with the elevation of FT4 levels was defined as clinical hyperthyroidism[14],[15].

Serum antibodies to TPO and ATg were determined in all participants by immunometric assays. Levels higher than 35 IU/ml for TPO and 40 IU/ml for ATg were considered abnormally high. Patients with a SLEDAI score of more than or equal to 6 were considered clinically active[14],[15].

Statistical analysis

Data analysis was done using SPSS, version 24 (Statistical Package for the Social Sciences for Windows statistical package; IBM Corp., Armonk, New York, USA). The relationship between categorical variables in small samples was tested by the χ2 test or by Fisher's exact test. The results of different variables were presented as mean ± SD. The mean ± SD values were compared between both groups using the Mann–Whitney test depending as the distribution was not normal. A P value less than 0.05 was considered statistically significant.


  Results Top


Seventy hundred (70%) of SLE patients with nephritis had abnormal TSH levels with a mean of (5.9 ± 2.6 mU/l) while 35% in SLE patients without nephritis was with a mean of (4.1 ± 1.6 mU/l) with statistically significant differences (P < 0.001). Also, SLE patients with nephritis had a significantly lower mean of FT4 (0.4 ± 0.5 ng/dl) while in SLE patients without nephritis the mean is (1.4 ± 0.3 mg/dl) with statistically significant differences (P < 0.001). SLE patients with nephritis had significantly higher thyroid autoantibodies (ATg and TPO) than SLE patients without nephritis (90 vs. 55%, 60 vs. 30%, and 65 vs. 30%, respectively). While the mean of complement 3 (C3) and complement 4 (C4) were lower in SLE patients with nephritis compared with SLE patients without nephritis (51.8 ± 17.6 vs. 103.9 ± 24.8 and 8.8 ± 3.6 vs. 35.4 ± 23.5, respectively) [Table 1].
Table 1: Comparison between the two studied groups according to different parameters

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All patients in both groups have positive antinuclear antibodies and increased anti-DNA and Anti-Smith. However, the means of urea and creatinine were higher in SLE patients with nephritis than SLE patients without nephritis (43.8 ± 14.7 vs. 38.6 ± 8.5 and 2.5 ± 1.6 vs. 2.3 ± 2.0, respectively). Of the SLE patients 10% with nephritis had a SLEDAI score less than 6 and 90% of them had a score more than 6, while the score of SLE patients without nephritis less than 6 was 35% and more than 6 was 65% [Table 2].
Table 2: Comparison between the two studied groups according to different parameters

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There were no statistically significant relations between thyroid autoantibodies abnormalities, ATg, TPO, and urine albumin/creatinine ratio, while there were statistically significant relations between thyroid autoantibodies abnormalities, ATg, and C3, C4, and SLEDAI score in SLE with nephritis [Table 3].
Table 3: Relation between thyroid autoantibody abnormalities and different parameters in systemic lupus erythematosus with nephritis (N=20)

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There were statistically significant differences between thyroid autoantibodies abnormalities including ATg and TPO, and C3, urine albumin/creatinine ratio, SLEDAI score, and C4 in SLE without nephritis [Table 4].
Table 4: Relation between thyroid autoantibody abnormalities and different parameters in systemic lupus erythematosus without nephritis (N = 20)

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  Discussion Top


The autoimmune nature of both thyroid disease and SLE makes the association between an expected sequence in SLE patients. There is a shred of strong evidence suggesting a genetic background for the association between SLE and thyroid disease. The development of both SLE and thyroid disease concomitantly rather than SLE only is strongly suggested in patients carrying a particular R620W polymorphism in the PTPN22 gene encoding a T-cell protein[16].

A site on chromosome 5 (5q14.3-15) was considered a susceptible gene in families with both SLE and AT[17].

This study reported that 70% of SLE patients with nephritis had abnormal TSH levels with a mean of 5.9 ± 2.6 mU/l while 35% in SLE patients without nephritis had a mean of 4.1 ± 1.6 mU/l with statistically significant differences (P < 0.001). Also, SLE patients with nephritis had a significantly lower mean of FT4 (0.4 ± 0.5 Ng/dl) while in SLE patients without nephritis the mean was 1.4 ± 0.3 mg/dl with statistically significant differences (P < 0.001). The most common thyroid disease in patients with lupus is hypothyroidism. Primary hypothyroidism occurs in 15–19% of patients with lupus[18],[19].

Several studies have confirmed that a relatively significant number of SLE patients had ATA, with values ranging from 20 to 45% in SLE patients, compared with 10% in the general population[17]. In contrast to this study, there was a study that assessed SLE patients in 6 months and reported that the levels of ATA were the same in both SLE patients (21%) and healthy population (16%)[20].

This study proved that SLE patients with nephritis had statistically significantly higher levels of thyroid autoantibodies (90%) compared with SLE patients without nephritis (55%) with statistically significant differences (P = 0.013). This comes in agreement with the studies by Weetman and Walport[13], Magaro et al.[21], and Kausman and Isenberg[22], who reported a significantly high prevalence of thyroid antibodies (51, 45, and 21%, respectively) in SLE patients.

In agreement with Pyne and Isenberg[6], who found a higher prevalence of thyroid antibodies in lupus patients with thyroid disease (68%), we found that SLE patients with nephritis had significantly higher positive TPO and ATg than SLE patients without nephritis with statistically significant differences (P < 0.05).

The cumulative positive rate of ATgAb and TPOAb was higher in SLE patients than healthy controls in a systemic review and meta-analysis published in 2015[23]. This study comes in agreement with other Egyptian studies[24],[25],[26]. It has not yet been established whether the ATA fluctuates with the SLE disease activity status in patients with and without nephritis. In the present study, ATA levels had a statistically significant correlation with disease activity assessed by SLEDAI and its components suggesting that the production of ATA is strongly related to the disease activity and progression in SLE patients.


  Conclusion Top


SLE patients with lupus nephritis had significantly higher thyroid autoantibodies than SLE patients without nephritis with significant positive correlations between these autoantibodies and SLE disease activity. Thyroid autoantibodies are important, new, and potential prognostic factors predicting poor outcomes in SLE patients with lupus nephritis correlating with SLEDAI. Further large-scale, multicenter, and prospective studies are needed to confirm these findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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