Correlation Analysis Between Baseline HTSH Level And Hypothyroidism After Immunotherapy For Malignant Tumors

Objective To analyze the related risk factors of hypothyroidism after immunotherapy in patients with malignant tumor and explore the relationship between baseline hypersensitivity thyroid stimulating hormone(hTSH)levels and hypothyroidism after immunotherapy for malignant tumors.Methods48 patients with malignant tumors who were hospitalized in the Shizhong District People’s Hospital of Zaozhuang City from January 2020 to January 2022 were selected as the research objects.All patients were histopathologically diagnosed as malignant tumors.Performance status(PS)score 0~2 points.All patients received immune checkpoint inhibitors therapy,including Camrelizumab 200mg(36 cases),Sintilimab 200mg(9 cases),Tislelizumab200mg(2 cases),Atezolizumab 1200mg(1 case),three-week course of treatment,until intolerable adverse events or disease progression occurred.Many factors,such as patients’ age,gender,smoking history,history of diabetes,history of hypertension,history of coronary heart disease,anti-thyroglobulin antibody(TG-Ab),anti-thyroid peroxidase antibody(TPO-Ab),baseline thyroid function,body mass index(BMI),triglycerides(TG),drug name,treatment history and combined treatment factors have been retrospectively analyzed.The risk factors for hypothyroidism after immunotherapy for malignant tumors were selected,and the relationship between baseline hTSH levels and hypothyroidism after immunotherapy for malignant tumors were further analyzed.In the statistical analysis of this study,Continuous variables were expressed as mean ± standard deviation,and categorical variables were expressed as the number of cases or percentages.Univariate analysis and multiple regression equations were used to analyze the differences in the mean and proportion of hTSH after immunotherapy for each factor.In addition,we utilize generalized additive models to identify nonlinear relationships.If non-linear correlations were observed,we employed a two-segment linear regression model to calculate the threshold effect of baseline hTSH on post-treatment hTSH based on smooth plots.The maximum likelihood method was used to calculate the inflection point when there was a clear rise in the smooth curves of baseline hTSH and post-immunotherapy hTSH.All analyses were performed using a statistical software Empower Stats.P<0.05 was considered statistically significant.Results Among the 48 patients who received PD1/PD-L1 inhibitor therapy,30 cases(62.50%)had normal thyroid function,18 cases(37.50%)had hypothyroidism.Among them,4 cases(8.33%)had clinical hypothyroidism,and 14 cases(29.17%)had subclinical hypothyroidism.By univariate analysis of the baseline data of 48 patients,it was found that age,gender,smoking history,hypertension history,diabetes history,coronary heart disease history,radiotherapy history,chemotherapy history,targeted therapy history,combined radiotherapy history,combined chemotherapy history,TG,BMI,TPO-Ab,TG-Ab,drug name were not related to hypothyroidism after immunization treatment(P>0.05).However,it was found that baseline hTSH(P<0.001)and combined targeted therapy(P=0.005)were related to hTSH after immunotherapy,and the difference was statistically significant.To further investigate the association of baseline hTSH and combined targeted therapy with post-immunotherapy hTSH,we used multiple regression equations to assess their associations.Meanwhile,we showed unadjusted and adjusted models.In the unadjusted model,The increase of baseline hTSH was positively correlated with post-immunotherapy hTSH(β=1.5,95% CI: 0.9~2.1,P<0.001),and combined targeted therapy was positively correlated with post-immunotherapy hTSH(β=3.2,95 %CI: 1.1~5.3,P=0.005).In the minimum adjustment model(adjusted for age and sex),the increase of baseline hTSH and combined targeted therapy were still positively correlated with post-immunotherapy hTSH(β=1.5,95%CI: 0.9~2.1,P<0.001;β = 3.3,95% CI:1.1 ~ 5.5,P = 0.005).In the fully adjusted model,we detected a positive correlation between the increase of baseline hTSH and post-immunotherapy hTSH(β=1.6,95% CI: 1.0~2.2,P<0.001),but we did not detect the correlation between combined targeted therapy and post-immunotherapy hTSH(β=1.4,95%CI:-1.4~4.2,P=0.342).Since both baseline hTSH and post-immunotherapy hTSH were continuous variables,it was very necessary to analyze the nonlinear relationship betweenthem.After adjusting gender,age,smoking history,hypertension history,diabetes history,coronary heart disease,TG,radiotherapy history,chemotherapy history,targeted therapy history,combined radiotherapy,combined chemotherapy,combined targeted therapy,BMI,TPO-Ab,TG-Ab,drug name and other factors,a non-linear relationship between baseline hTSH and post-treatment hTSH was found.Through a two-segment linear regression model,we calculated that the inflection point was 3.42 μIU/m L.When the baseline hTSH was less than 3.42 μIU/m L,there was no significant relationship between the baseline hTSH and the post-immunotherapy hTSH(β=0.12,95%CI:-1.17~1.41,P=0.855).However,when baseline hTSH was more than3.42 μIU/m L,baseline hTSH was significantly associated with post-immunotherapy hTSH(β=3.10,95%CI:1.90~4.30,P<0.001).Therefore,we concluded that when the baseline hTSH was more than 3.42 μIU/m L,for every 1 μIU/m L increase in baseline hTSH,hTSH increases by 3.10 μIU/m L after treatment.Conclusions The increase of baseline hTSH is risk factor for hypothyroidism after immunotherapy in patients with malignancy.When the baseline hTSH is greater than 3.42 μIU/m L,the incidence of hypothyroidism after immunotherapy will significantly increase.It is recommended to detect the level of hTSH in patients before immunotherapy,so as to diagnose and intervene hypothyroidism as early as possible,better manage patients and ensure drug safety for patients.