代谢综合征患者血清25(OH)D和GDF15水平表达与并发甲状腺结节发生恶性风险的相关性研究

Study on the Correlation between the Expression of Serum 25(OH)D and GDF15 Levels and the Risk of Malignancy in Combined Thyroid Nodules in Patients with Metabolic Syndrome

目的探讨代谢综合征(metabolic syndrome,MS)患者血清25羟基维生素D[25(OH)D],生长分化因子15(growth differentiation factor 15,GDF-15)水平表达与并发甲状腺结节(thyroid nodules,TN)发生恶性风险的相关性。方法选取2019年8月~2023年8月在新疆医科大学第一附属医院就诊的185例MS患者作为研究对象,按照甲状腺超声检查结果将其分为MS组(n=73)和MS+TN组(n=112),并根据甲状腺结节恶性分级将MS+TN组患者分为良性组(n=89)及恶性组(n=23);另选取同期体检的68例体检健康者作为对照组。采用酶联免疫吸附法(ELISA)测定各组血清25(OH)D和GDF-15水平;Pearson分析血清25(OH)D和GDF-15水平与MS并发TN患者临床指标之间的相关性;多因素Logistic回归分析MS并发TN患者发生恶性TN的影响因素;绘制受试者工作特征(ROC)曲线评估血清25(OH)D和GDF-15水平对MS并发恶性TN的诊断价值。结果对照组、MS组、MS+TN组血清25(OH)D(30.41±6.73ng/ml,27.23±6.15 ng/ml,24.67±4.38 ng/ml)和GDF-15(167.99±22.56 ng/L,239.75±25.92 ng/L,286.63±26.04 ng/L)水平比较,差异具有统计学意义(F=22.219,472.113,均P<0.05);且与良性组相比,恶性组患者血清25(OH)D(26.28±4.53 ng/ml vs 18.44±3.79 ng/ml)水平明显降低,GDF-15(276.93±24.53 ng/L vs 324.17±31.89 ng/L)水平明显升高,差异具有统计学意义(t=7.631,7.718,均P<0.05)。恶性组患者BMI,年龄、FPG,TG,TSH和TGAb水平明显高于良性组,差异具有统计学意义(t=2.868,3.523,3.542,3.603,4.581,5.516,均P<0.05).Pearson相关分析,MS并发TN患者血清25(OH)D水平与FPG,TSH,TG和TGAb水平均呈负相关(r=-0.302,-0.482,-0.524,-0.546,均P<0.05),GDF-15水平与TG,TSH,TGAb和FPG水平均呈正相关(r=0.467,0.541,0.578,0.623,均P<0.001)。多因素Logistic回归分析,GDF-15(OR=1.673,95%CI:1.146~2.442)为MS患者恶性TN发生的危险因素(P<0.05),25(OH)D(OR=0.744,95%CI:0.604~0.916)为恶性TN发生的保护因素(P<0.05);血清25(OH)D和GDF-15水平单独及联合诊断MS并发恶性TN的AUC分别为0.813,0.799,0.930,联合诊断优于单独诊断(Z=2.088,2.021,P=0.037,0.043)。结论MS并发TN患者血清25(OH)D,GDF-15水平与其结节性质明显相关,血清25(OH)D水平降低和GDF-15水平升高是MS患者发生恶性TN的危险因素。

Objective To investigate the correlation between the expression of serum 25hydroxyvitamin D[25(OH)D]and growth differentiation factor 15(GDF-15)levels and the risk of malignancy in patients with metabolic syndrome(MS)and the development of combined thyroid nodules(TN).Methods From August 2019 to August 2023,185 MS patients who visited the First Affiliated Hospital of Xinjiang Medical University were regarded as the study subjects,according to the results of thyroid ultrasound examination,they were separated into MS group(n=73)and MS+TN group(n=112).According to the malignant grading of thyroid nodules,MS+TN patients were separated into benign group(n=89)and malignant group(n=23).Another 68 healthy individuals who underwent physical examinations were regarded as control group.Enzyme-linked immunosorbent assay(ELISA)was applied to determine the levels of serum 25(OH)D and GDF-15 in each group.Pearson was applied to analyze the correlation between serum 25(OH)D and GDF-15 levels and clinical indicators in MS in TN patients.Multivariate Logistic regression was applied to analyze the influencing factors of malignant TN in patients with MS combined with TN.Receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic value of serum 25(OH)D and GDF-15 levels in MS with malignant TN.Results Comparison of serum 25(OH)D(30.41±6.73 ng/ml,27.23±6.15 ng/ml,24.67±4.38 ng/ml)and GDF-15(167.99±22.56 ng/L,239.75±25.92 ng/L,286.63±26.04 ng/L)levels in control,MS and MS+TN groups,the differences were statistically significant(F=22.219,472.113,all P<0.05).Compared with the benign group,the serum 25(OH)D(26.28±4.53 ng/ml vs 18.44±3.79 ng/ml)level in the malignant group was obviously reduced,while the GDF-15(276.93±24.53 ng/L vs 324.17±31.89 ng/L)level was obviously increased,the differences were statistically significant(t=7.631,7.718,all P<0.05).The BMI,age,FPG,TG,TSH and TGAb levels of patients in the malignant group were obviously higher than those in the benign group,the difference were statistically significant(t=2.868,3.523,3.542,3.603,4.581,5.516,all P<0.05).Pearson correlation analysis,and the serum 25(OH)D level in MS patients with TN was negatively correlated with FPG,TSH,TG and TGAb levels(r=-0.302,-0.482,-0.524,-0.546,all P<0.001),while GDF-15 level was positively correlated with TG,TSH,TGAb and FPG levels(r=0.467,0.541,0.578,0.623,all P<0.05).Multivariate logistic regression analysis,GDF-15(OR=1.673,95%CI:1.146~2.442)was a risk factor for the occurrence of malignant TN in MS patients(P<0.05),and 25(OH)D(OR=0.744,95%CI:0.604~0.916)was a protective factor for the occurrence of malignant TN,the AUC values of serum 25(OH)D and GDF-15 levels in the diagnosis of MS combined with malignant TN were 0.813,0.799 and 0.930,respectively,and the combination was superior to the single diagnosis(Z=2.088,2.021,P=0.037,0.043).Conclusion The levels of serum 25(OH)D and GDF-15 in patients with MS combined with TN are obviously correlated with nodular nature.The decrease in serum 25(OH)D level and the increase in GDF-15 level are risk factors for malignant TN in MS patients.