儿童系统性红斑狼疮合并甲状腺功能异常危险因素分析

Risk factors of childhood systemic lupus erythematosus with thyroid dysfunction

目的探讨系统性红斑狼疮(SLE)患儿合并甲状腺功能异常的危险因素以及甲状腺激素与狼疮性肾炎(LN)肾脏损伤的关系。方法回顾性病例总结,选取2019年1月至2021年12月于郑州大学第一附属医院儿科确诊SLE的253例患儿为病例组,选取同期同年龄段进行健康体检、无不适症状的70名健康儿童作为对照组,根据甲状腺功能检查结果将病例组分为甲状腺功能正常组和甲状腺功能异常组。组间比较采用独立样本t检验、χ^(2)检验、Mann-Whitney U检验,多因素分析采用Logistic回归分析,采用Spearman进行相关性分析。结果病例组253例患儿中男44例、女209例,就诊年龄14(12,16)岁;70名对照组儿童中男24名、女46名,就诊年龄13(10,13)岁。病例组甲状腺功能异常的发生率高于对照组[48.2%(122/253)比8.6%(6/70),χ²=36.03,P<0.05]。131例甲状腺功能正常组中男17例、女114例,就诊年龄14(12,16)岁;122例甲状腺功能异常组中男28例、女94例,就诊年龄14(12,16)岁,其中正常甲状腺病态综合征51例(41.8%)、亚临床甲状腺功能减退症25例(20.5%)、亚临床甲状腺功能亢进症18例(14.8%)、甲状腺功能低减症12例(9.8%)、桥本甲状腺炎10例(8.2%)、甲状腺功能亢进症4例(3.3%)、毒性弥漫性甲状腺肿2例(1.6%)。甲状腺功能异常组的SLE疾病活动度评分、甘油三酯、胆固醇、尿红细胞、尿白细胞、24 h尿蛋白、D-二聚体、血浆纤维蛋白原及铁蛋白水平均高于甲状腺功能正常组(Z=2.80、3.07、3.07、2.48、3.16、2.40、3.99、2.68、2.55,均P<0.05),甲状腺功能异常组游离甲状腺激素及补体C3水平均低于甲状腺功能正常组[10.6(9.1,12.7)比11.3(10.0,12.9)pmol/L、0.46(0.27,0.74)比0.57(0.37,0.82)g/L,Z=2.18、2.42,均P<0.05]。Logistic回归分析显示血甘油三酯及血浆D-二聚体水平升高均是SLE患儿合并甲状腺功能异常的危险因素(OR=1.40、1.35,95%CI 1.03~1.89、1.00~1.81,均P<0.05)。病例组共161例合并LN,全部行肾脏穿刺及病理活检,其中Ⅰ型LN 11例(6.8%)、Ⅱ型LN 11例(6.8%)、Ⅲ型LN 31例(19.3%)、Ⅳ型LN 92例(57.1%)、Ⅴ型LN 16例(9.9%)。不同病理类型间LN患儿血清促甲状腺激素和游离三碘甲状腺原氨酸水平差异均有统计学意义(均P<0.05),Ⅳ型LN患儿的游离三碘甲状腺原氨酸水平低于Ⅰ型[3.4(2.8,3.9)比4.3(3.7,5.5)pmol/L,Z=3.75,P<0.05]。Spearman相关分析显示,不同病理类型LN患儿游离三碘甲状腺原氨酸水平与肾脏病理活动性指数评分呈低度负相关(r=-0.228,P<0.05),血清促甲状腺激素水平与肾脏病理活动性指数评分存在低度正相关(r=0.257,P<0.05)。结论儿童SLE合并甲状腺功能异常的发生率较高。合并甲状腺功能异常的SLE患儿SLE疾病活动度指数更高、肾脏损伤更重。血甘油三酯及血浆D-二聚体水平升高是儿童SLE合并甲状腺功能异常的危险因素,甲状腺激素水平与LN患儿肾脏损伤可能存在一定相关性。

Objective To investigate the risk factors of childhood systemic lupus erythematosus(SLE)with thyroid dysfunction and to explore the relationship between thyroid hormone and kidney injury of lupus nephritis(LN).Methods In this retrospective study,253 patients who were diagnosed with childhood SLE and hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2021 were enrolled in the case group,and 70 healthy children were the control cases.The patients in the case group were divided into the normal thyroid group and the thyroid dysfunction group.Independent t-test,χ^(2) test,and Mann-Whitney U test were used for comparison between the groups,Logistic regression analysis was used for multivariate analysis,and Spearman correlation.Results A total of 253 patients,there were 44 males and 209 females in the case group,and the age of onset was 14(12,16)years;a total of 70 patients,24 males and 46 females were in the control group,and the age of onset was 13(10,13)years.The incidence of thyroid dysfunction in the case group was higher than that in the control group(48.2%(122/253)vs.8.6%(6/70),χ²=36.03,P<0.05).Of the 131 patients,there were 17 males and 114 females in the normal thyroid group,and the age of onset was 14(12,16)years.Of the 122 patients in the thyroid dysfunction group,28 males and 94 females were in the thyroid dysfunction group,and the age of onset was 14(12,16)years.Of the 122 had thyroid dysfunction,including 51 cases(41.8%)with euthyroid sick syndrome,25 cases(20.5%)with subclinical hypothyroidism,18 cases(14.8%)patients with sub-hyperthyroidism,12 cases(9.8%)with hypothyroidism,10 cases(8.2%)with Hashimoto′s thyroiditis,4 cases(3.3%)with hyperthyroidism,and 2 cases(1.6%)with Graves disease.Compared to patients with normal thyroid function,the serum level of triglyceride,total cholesterol,urine white blood cell,urine red blood cell,24 h urine protein,D-dimer,and fibrinogen,ferritin and systemic lupus erythematosus disease activity Index-2000(SLEDAI-2K)score were higher in patients with thyroid dysfunction(Z=3.07,3.07,2.48,3.16,2.40,3.99,2.68,2.55,2.80,all P<0.05),while the serum level of free thyroxine and C3 were lower in thyroid disfunction patients(10.6(9.1,12.7)vs.11.3(10.0,12.9)pmol/L,and 0.46(0.27,0.74)vs.0.57(0.37,0.82)g/L,Z=2.18,2.42,both P<0.05).The higher level of triglyceride and D-dimer were the independent risk factors for childhood SLE with thyroid dysfunction(OR=1.40 and 1.35,95%CI 1.03-1.89 and 1.00-1.81,respectively,both P<0.05).There were 161 patients with LN in the case group,all of which were conducted with renal biopsies,including 11 cases(6.8%)with typesⅠLN,11 cases(6.8%)with typesⅡLN,31 cases(19.3%)with typesⅢLN,92 cases(57.1%)with typesⅣLN,and 16 cases(9.9%)with typesⅤLN.There were significant differences in the level of free triiodothyronine and thyroid stimulating hormone among different types of kidney pathology(both P<0.05);compared with types I LN,the serum level of free triiodothyronine was lower in typesⅣLN(3.4(2.8,3.9)vs.4.3(3.7,5.5)pmol/L,Z=3.75,P<0.05).The serum level of free triiodothyronine was negatively correlated with the acute activity index score of lupus nephritis(r=-0.228,P<0.05),while the serum level of thyroid stimulating hormone was positively correlated with the renal pathological acute activity index score of lupus nephritis(r=0.257,P<0.05).Conclusions There is a high incidence of thyroid dysfunction in childhood SLE patients.The higher SLEDAI and more severe renal damage were found in SLE patients with thyroid dysfunction compared to these with normal thyroid functions.The risk factors of childhood SLE with thyroid dysfunction are the higher level of triglyceride and D-dimer.The serum level of thyroid hormone is possibly related to the kidney injury of LN.