Study Of The Relationship Between Serum Thyroglobulin And Metastases As Well As The Treatment Response In Patients With Differentiated Thyroid Carcinoma

Part 1 Relation between pathology of papillary thyroid cancer and the stimulated serum thyroglobulin at the frist radioactive iodine therapy for metastasisObjectiveRetrospective analyzed the association and pattern between the pathology of papillary thyroid carcinoma (PTC) and the stimulated serum thyroglobulin (sTG) at the frist radioactive iodine (RAI) therapy for metastasis which would help deciding the next treatment program after the frist RAI for residual thyroid.MethodsReviewed the patients who received RAI therapy at our apartment from January 2014 to December 2015, including the patients pathologically comfirmed PTC after thyroidectomy, had the frist RAI adjuvant therapy at our apartment and TGAb was negative (≤115IU/L) which detected by CLIA. Then the patients whose TG weren’t detected by CLIA or the pathological information missed were excluded.There were 395 patients in our study. Analyzed the clinical information retrospectively (sex, age, interval from total thyroidectomy to initial RAI, sTG, TGAb and TSH levels) as well as pathological data including pathological subtype (PTC classical type, tall cell, columnar cell, diffuse sclerosing and oncocytic variants), No. of tumor involvement, No. of glands involvement, tumor diameter, embolus/vascular invasion, thyroid capsular invasion, extracapsular invasion, nerve invasion, complication diseases of thyroid cancer (such as Hashimoto’s thyroiditis, nodular goiter, Graves disease, simple goiter), No. of LN (including NLNM, NLND, CLNM, CLND) and NO. of thyroidectomies. Divided sTG into 4 levels, including< 2ug/L,≥2ug/L and< lOug/L,≥10ug/L and <100ug/L,≥100ug/L. SPSS 19.0 software was applied to analysis Statistics, and the groups with statistics signifincance after univariate analyses (x2 test/Fisher’s exact test) were taken into the multivariate ordinal logistic regression analysis. P-value of <0.05 was considered significant.Results395 cases of patients, including 126 men and 269 women (M:F=1:2.13), the mean and range of ages were 40.43±12.9 and 12～77 years.189 cases sTG<2μg/L (47.8%), 91 cases 2-10μg/L (23.0%),70 cases 10～100μg/L (17.7%),45 cases≥100μg/L (11.3%). Tumor diameter, embolus/vascular invasion, thyroid capsular invasion, extracapsular invasion, complication diseases of thyroid cancer, No. of LN (including NLNM, NLND, CLNM, CLND) and NO. of thyroidectomies were associated with sTG signifincantly (χ2=15.045,35.392,20.967,26.565,39.991,17.640,10.880,30.743, 15.450, P=0.020,0.000,0.000,0.000,0.000,0.001,0.012,0.000,0.001) after univariate analyses, but only thyroid capsular invasion (Estimate=-0.459, P=0.033), extracapsular invasion (Estimate=-0.502, P=0.020), complication diseases of thyroid cancer (HT, Estimate=-2.165, P=0.001; nodular goiter, Estimate=-0.854, P=0.000), NO. of thyroidectomies (Estimate=-0.823, P=0.001), No. of NLNM (<5, Estimate=-1.135, P=0.000) were the signifincant factors for sTG after multivariate analyses.ConclusionThe pathological factors associated with sTG before the first RAI therapy for the metastases were tumor diameter, embolus/vascular invasion, thyroid capsular invasion, extracapsular invasion, thyroid associated diseases, No. of LN (including NLNM, NLND, CLNM, CLND) and NO. of thyroidectomies. Among all the factors above, thyroid capsular invasion, extracapsular invasion, thyroid associated diseases (HT/ nodular goiter), NO. of thyroidectomies and No. of NLNM independently influenced sTG, what’more, thyroid capsular invasion/extracapsular invasion positive and having reoperation indicated a higher sTG, a lower sTG conveyed by complication diseases of thyroid cancer (HT/nodular goiter) and No. of NLNM<5. The conclusion could be used in clinical work to predict sTG and contributed to the decision-making of the next treatment program.Part 2 The predictive value of serum thyroglobulin and its variation for metastases of papillary thyroid cancerObjectiveTo investigate the association and pattern between the metastases of PTC and the TG before and after thyroid hormone withdrawal as well as its variation.MethodsReviewed the patients who received RAI therapy at our apartment from January 2014 to December 2015, including the patients pathologically comfirmed DTC after thyroidectomy, had the first RAI therapy for metastases at our apartment, the repressed and stimulated TG before RAI were negative (≥115IU/L by CLIA, or<30% by RIA), then the patients who failed to have successful ablation of residual thyroid tissue and/or had the TSH level corresponding to the repressed TG before the first RAI therapy for metastases was>5uIU/ml (RIA) were excluded. There were 291 cases meeted the standard above. The data of patients’age and gender were gathered, the clinical information including the repressed TG (rTG) before the first RAI therapy for metastases and the corresponded TGAb and TSH (called rTG, rTGAb and rTSH), the sTG and the corresponded TGAb and TSH (called sTG, sTGAb and sTSH), 131I-Whole body Scan, thyroid static imaging, dynamic salivary imaging, thyroid radioiodine uptake(24h),18F-FDG, PET/CT, cervical ultrasonic examination, neck and chest CT, chest DR were collected. SPSS 19.0 software was applied to analysis Statistics, x2 test was used to compare the difference of the age and gender between metastases groups, rTG, sTG, △TG (rTG-sTG), rTSH, sTSH, rTGAb and sTGAb didn’t conform to Normal distribution, so Kruskal-Wallis rank test were needed, then receiver operating characteristic curves (ROC) and the cut off value of rTG and sTG as well as the area under the ROC curve (AUC) were worked out to predict the metastases of PTC. P-value of<0.05 was considered significant.Results291 cases of patients, including 78 men and 213 women (M:F=1:2.73), the mean and range of ages were 41.12±13.4 and 12～77 years. Lymph node/soft tissue metastasis, distant metastasis and non-transfer group had 138 cases (47.4%),27 cases (9.3%) and 126 cases (43.3%) respectively. The range of rTG of lymph node/soft tissue metastasis group was 0.04～500μg/L, sTG (0.04-1100μg/L), △TG (-136.3～749.71μg/L). The range of rTG of distant metastasis group was 0.1～1439μg/L, sTG (0.14～5321μg/L), △TG (-4.99～5080.8μg/L). The range of rTG of non-transfer group was 0.04～7.51μg/L, sTG (0.04～11.35μg/L), △TG (-7.38-10.49ug/l).The univariate analyses result showed that rTG, sTG, ATG and sTGAb were connected with different metastasis signifincantly (p=0.000,0.000,0.000,0.009). The mean rTG rank value of three groups were 170.35,250.80 and 96.88 respectively; the mean sTG rank value were 180.46,253.20 and 85.29; the mean △TG rank value were 173.17,239.00 and 96.32. Area under the ROC curves with regard to lymph node/soft tissue metastasis were 0.765,0.847, the cut off value were 0.45μg/L,2.05μg/L with sensitivity of 75.4%,74.6%, specificity of 69.8%,82.5%, and Youden index were 0.456,0.571; The area under the ROC curves with regard to distant metastasis were 0.966,0.977, the cut off value were 9.20μg/L,26.60μg/L with sensitivity of 77.8%, 81.5%, specificity of 100.0%,100.0% and Youden index were 0.778,0.851.ConclusionThe TG before and after thyroid hormone withdrawal as well as the variation between them at the first RAI therapy for the metastasis have the predictive value of lymph node/soft tissue metastasis and distant metastasis, what’s more, the order of TG value with metastasis was distant metastasis> lymph node/soft tissue metastasis> non-transfer, and the rTG>9.2μg/L or sTG>26.6μg/L mean a higher risk for distant metastasis.Part 3 The prognostic value of serum thyroglobulin for treatment response of RAIObjectiveTo investigate the regulation between the sTG before the initial RAI and the treatment response of RAI.MethodsRetrospective the patients who received RAI therapy at our apartment from January 2014 to February 2016, including the patients pathologically comfirmed DTC after thyroidectomy, had the ablation therapy at our apartment, the sTG before the RAI was detected by CLIA and TGAb was negative (≤115IU/L, CLIA), then the patients who didn’t finish the RAI therapy or lost were excluded, as well as the patients whose stimulated TSH level before the initial RAI was< 30μIU/ml (RIA), what’s more, the patients whose clinical or pathological information missed would be excluded too There were 190 cases meeted the standard above.Analyzed the clinical and pathological information retrospectively, including sex, age, NO. of thyroidectomies, interval from total thyroidectomy to initial RAI, pathological subtype (PTC classical type and the other variants), No. of tumor involvement, tumor diameter, embolus/vascular invasion, thyroid capsular invasion, extracapsular invasion, nerve invasion, complication diseases of thyroid cancer (such as Hashimoto’s thyroiditis, nodular goiter, Graves disease, simple goiter), No. of LN (including NLNM, NLND, CLNM, CLND) and the sTG, TGAb, TSH of the initial RAI. SPSS 19.0 software was applied to analysis Statistics, univariate analyses was used to compare the difference between clinical factors and the groups of responses to RAI (x2 test/Fisher’s exact test if comformed to normal distribution, or the Kruskal-Wallis rank test would be needed), the factors with statistics signifincance were taken into the multinomial logistic regression analyses. P-value of <0.05 was considered significant.Results190 cases of patients, including 70 men and 120 women (M:F=1:1.71), the mean and range of ages were 41.66±12.3 and 13～74 years.120 cases excellent response (63.2%),5 cases biochemical incomplete response (7.9%), structural incomplete response (20.5%), indeterminate response (8.4%). The range of follow-up was 4-25 months, and all the patients included received 2 times of RAI therapy, the range of cumulative dose were 200-395mCi.107cases(56.3%) of the sTG before the initial RAI≤10ug/l, and 83cases (43.7%)>10ug/l. Embolus/vascular invasion, extracapsular invasion, No. of NLNM and CLNM, sTG before initial RAI, cumulative dose were associated with different responses to RAI signifincantly after univariate analyses, and sex, age, NO. of thyroidectomies, interval from total thyroidectomy to initial RAI, pathological subtype, No. of tumor involvement, No. of glands involvement, thyroid capsular invasion, nerve invasion, complication diseases of thyroid cancer, No. of NLND and CLND, period of follow-up weren’t (P>0.05). The factors with significance were taken into multinomial logistic regression analyses, and the excellent response group was regard as reference for each other three groups. No. of NLNM and sTG before initial RAI got into the final regression model, and sTG was significantly correlated with biochemical/structural incomplete response and indeterminate response respectively (P=0.000,0.000,0.001), and higher sTG level along with higher possibility of biochemical/structural incomplete response (OR=0.020,0.025; 95%CI:-0.002～-0.173,0.006～0.102), but possibility of indeterminate response reduced (OR=0.063,95%CI:0.051～1.018). No. of NLNM was significantly correlated with structural incomplete response (P=0.022), more NLNM indicated structural incomplete response (OR=0.232; 95%CI:0.066-0.812).ConclusionEmbolus/vascular invasion, extracapsular invasion, No.of NLNM and CLNM, sTG before the initial RAI, cumulative dose were associated with different responses to the initial RAI signifincantly, No. of NLNM and sTG before initial RAI got into the final regression model, and No. of NLNM>5 suggested risks of structural incomplete response, sTG>10μg/L implied with higher risks of biochemical/structural incomplete response but lower risks of indeterminate response.