| Background:Hypothyroidism has been found to be the most common abnormality of thyroid function in patients with Sjogren’s syndrome(SS).However,research on the relationship between hypothyroidism and SS is scarce and not sufficiently detailed.The causal relationship between SS and hypothyroidism is still unclear.Objectives:1.To further confirm the prevalence of hypothyroidism in primary Sj?gren’s syndrome(pSS)patients,to clarify the clinical characteristics of pSS patients with hypothyroidism and to identify the risk factors of hypothyroidism in pSS patients.2.To explore the causal relationship between hypothyroidism and SS and to analyze the association between hypothyroidism and SS,as well as to provide ideas for the study of the mechanism of hypothyroidism developing in SS.Methods:1.814 cases of pSS patients and 1565 cases of sex-and age-matched healthy population were included.2.Compared the prevalence of hypothyroidism and the positive rate of thyroid autoantibodies between pSS patients and control population.3.Collected clinical data and laboratory indices of patients,compared the differences between patients with pSS-hypothyroidism and patients with pSS-euthyroidism.Comparisons between two groups of normally distributed quantitative variables were performed by t-test,and comparisons between two groups of non-normally distributed quantitative variables or ranked data were performed by rank sum test.The chi-square test was used for comparison of differences between two groups of categorical variables.Binary logistic regression analysis was used for multi-factor analysis.When P<0.05,the difference was indicated as statistically significant.4.Collected genome-wide association study data for hypothyroidism and SS,selected single nucleotide polymorphism as instrumental variables,and then the use TwoSampleMR package in R 4.2.2 software for two-sample mendelian randomization analysis.Results:1.The prevalence of hypothyroidism in pSS patients was not significantly different from that in healthy controls(13.02%vs12.14%,P=0.573),but the prevalence of clinical hypothyroidism was higher in pSS patients than that in healthy controls(5.04%vs1.09%,P<0.001)while the prevalence of subclinical hypothyroidism was lower in healthy controls than in pSS patients(7.99%vs 11.05%,P--0.018).The rate of thyroid peroxidase antibody(TPOAb)positivity was higher in pSS patients than in healthy controls(20.76%vs 11.50%,P<0.001).There was no significant difference in the rate of thyrotropin receptor antibody(TRAb)and thyroglobulin antibody(TgAb)positivity between the two groups.2.Compared with the pSS-euthyroidism patients,pSS patients with hypothyroidism had lower positive rate of smoking history,lower levels of erythrocytes,hemoglobin,absolute monocytes,apolipoprotein A/B,glomerular filtration rate(P<0.05),and higher levels of prothrombin time,triglycerides,apolipoprotein B,creatinine,β2 microglobulin,cystatin,myoglobin,creatine kinase isoenzyme,troponin I,Sj?gren’s syndrome type B(SSB)antibodies,immunoglobulin E and ESR,as well as the higher prevalence of cirrhosis,hyperlipidemia and anemia(P<0.05).3.Multifactorial logistic regression analysis showed that elevated creatinine[odd ratio(OR)=1.009 95%Confidence intervals(CI)1.001-1.018,P=0.038],elevated triglycerides(OR=22.463,95%CI1.584-3.831,P<0.001),decreased hemoglobin(OR=0.984,95%CI0.971－0.998,P--0.022),and cirrhosis(OR=3.784,95%CI 1.447-9.894,P--0.007)were independent risk factors for the development of hypothyroidism in patients with pSS.4.Hypothyroidism was a risk factor for the development of SS(IVW:(OR=1.146,95%CI 1.013-1.297,P=0.031)and SS was a risk factor for the development of hypothyroidism(IVW:OR=1.169,95%CI 1.108-1.233,P<0.001).There was a bidirectional causal relationship between hypothyroidism and SS.Conclusion:Compared to the general population,the prevalence of clinical hypothyroidism is higher in patients with pSS.Patients with pSS combined with elevated creatinine,elevated triglycerides,decreased hemoglobin and cirrhosis are at high risk for hypothyroidism.There is a bidirectional causal relationship between hypothyroidism and SS. |
