Analysis On The Incidence Of Graves' Disease And Hashimoto's Thyroiditis In 28 Years And Pathological Study On Expression Of VEGF, TGF-β, CD20 And CD45RO In Graves' Disease And Hashimoto's Thyroiditis.

Object and method: Graves' Disease(GD) and Hashimoto's thyroiditis(HT) belong to autoimmune thyroid disease. Environment such as iodine intake, infection, emotion, stress and so on breakdown the tolerance to thyroid autoantigen in genetic susceptible population and induce GD and HT. The increase of iodine intake have a positive cooperativity with HLA allele in progression of GD and HT. The first part of present study was designed to statistically analyze the clinical-pathologic data of patients with pathologically confirmed GD and HT in 1978-2005 years taken from the files in the Department of pathology, Tianjin Medical University with Run test, Cox-stuart test, ANOVA, t or t' test and Chi-square test. We study the biopsy rate, proportion, range of age, the average age at diagnosis, sex ratio, complications of HT in our study, and analyze the change of the incidences of GD and HT in the past 28 years and to prove the relationship between iodine intake and these two diseases.Results:1. The sum of biopsies in 28 year was 243 403(average 8 693 cases/year). The average biopsy rates: thyroid disease (6 771 cases)2.78 %,GD(216 cases)0.89‰,HT(352 cases) 1.45‰. The biopsy rate in thyroid disease and GD showed a descending tendency since 1982 but a ascending tendency from 1995.Furthermore,GD showed a descending tendency during 2001 to 2005 again. The proportion of GD have a same tendency like biopsy rate. While the biopsy rate in HT and GD+HT showed a descending tendency from 1986 and a ascending tendency after 1996, they have a 1～4 years late. Though HT showed no descending tendency after that, the biopsy rate in GD+HT had a descending tendency in 2002～2005 accordingly and the proportion in HT showed a descending tendency in 2003～2005.2. The average age of GD was lower than HT(p＜0.05). The patients of GDⅠ-type andⅡ-type were younger thanⅢ-type(p＜0.05), the average age of HT: L-type＜O-type＜P-type(p＜0.05). The average age of GDⅢ-type was similar to HT L-type. There were the same conclusions as above in male and female patients. The average age of total and female patients of GD showed a ascending tendency from 1985 and a descending tendency from 1997, this tendency was not observed in male patients of GD and HT patients.3. In 28 years, the gender of GD and HT were apt to female. The total sex ratio of GD and HT were 1:3.41 and 1:15.76. In HT, there were more female patients than in GD(p＜0.05).4. Proportion of complications in HT: hyperthyroidism (7.95%), nodular goiter(6.25%),carcinoma(2.27%) were more in L-type, while hypothyroidism (2.56%) was more in P-type. The average age of HT with hyperthyroidism was lower than HT without hyperthyroidism(p＜0.05), the average age of HT with hypothyroidism was higher than HT without hypothyroidism(p＜0.05). The average age of two gender in HT with/without hyperthyroidism and nodular goiter were similar. The complications of HT were all apt to female.Conclusions:1. In 28 years, the biopsy rate and proportion of GD and HT showed phasic tendencies according to the change of iodine intake. In 1980's, the incidence of GD and HT showed a descending tendency because of low iodine water drinking. The incidence of GD and HT showed a ascending tendency after iodized salt was provided in 1994 and showed a descending tendency since 2000. This suggest a scientific iodine supplement would not induce the increase of GD and HT. Environment and genetic mutation play important roles in developments of GD and HT.2. The average age of GD was lower than HT. The patients' average age were more higher follow the progression from GD to HT. The average age of GDⅢtype was similar to HT-L type, only have 1 year difference. The average age of total and female patients of GD showed a descending tendency from 1997, which opposite to biopsy ratio in GD, suggested the operating age in female was lower than before.3. In 28 years, the gender of GD and HT were apt to female. In HT, there were more female patients than in GD. The change of iodine intake have no notable influence in sex ratio.4. The complications of HT: hyperthyroidism, nodular goiter, carcinoma were more in L-type, while hypothyroidism was more in P-type. Women who have suffered HT for a long time was prone to occur hypothyroidism. Hyperthyroidism were more in the beginning of HT. There were no differences in different gender's average age in HT with or without complications. The complications of liT were all apt to female. Object and method: The histotype of Graves' Disease(GD) and Hashimoto's thyroiditis(HT) was related to infiltrating lymphocytes in thyroid. Its biologic behavior is influenced significantly by regulation of autoimmune response and inflammation cytokines and vascularization correlation factor. VEGF and TGF-βwere reported to expressed highly in GD and HT. They have certain relationship with vasiformation, immunological regulation and interstitial fibrosis. In the second part of our study, we investigate the expression of VEGF,TGF-β, CD20 and CD45RO in GD and HT using immunohistochemical staining. Our aim is to detect the relaitiongship between their expression and histotype of GD and HT, vascularization in thyroid and regulation of autoimmune response. 115 cases from paraffin specimen of 1965～2004 years were selected randomly, including GD (n=57,Ⅰtype: 21cases,Ⅱtype: 20cases,Ⅲtype: 16cases) and HT(n=58, L-type: 21cases,O-type: 19cases,P-type: 18cases). t or t' test was used to comparing the average age in these cases, ANOVA was used to analyze the change of average number of thyroid follicle which have positive staining. Chi-square(Fisher) test was used to comparing the positive rate and intensity of staining.Results:1. VEGF and TGF-βwere main expressed in follicular epithelial cell cytoplasm, the positive mass of VEGF and TGF-βwas yellow to buffy with suffused or scattered distribution.2. Average number of VEGF positive thyroid follicle in GD (25.72 follicles/HPF)was lower than HT(56.27 follicles/HPF)(p＜0.05). In subtypes of GD, average number of VEGF positive thyroid follicle in I type andⅡtype (17.11 follicles/HPF, 23.07 follicles/HPF) were lower thanⅢtype (40.34 follicles/HPF) (p＜0.05). In subtypes of HT, average number of VEGF positive thyroid follicle in L-type andP-type (49.28 follicles/HPF, 51.02 follicles/FIPF) were lower than O-type (68.96 follicles/HPF) (p＜0.05). While the positive rate of VEGF in thyroid follicle: L-type (50.96%)＜O-type (67.62%)＜P-type (86.37%) (p＜0.05).3. The number of cases in which TGF-13 staining were positive both were 56 in GD and HT. In these cases, the ratio of TGF-13 positive follicles were almost 100%. The positive rate of TGF-β(98.28%) was similar to HT (96.55%) (p＜0.05).4. CD20 and CD45RO were main expressed in cytoplasm of infiltrating lymphocytes among thyroid follicle or follicular epithelial cell, the positive mass of VEGF and TGF-βwas yellow to buffy with suffused or scattered distribution.5. The positive rate of CD20 in GD(51.84%) was similar to HT(52.83%), the positive rate of CD45RO in GD(45.70%) was similar to HT(43.16%)(p＞0.05). In subtypes of GD and HT, there have the same conclusion. The ratio of CD20: CD45RO was 5:4～5:5.Conclusion:1. The expression of VEGF and TGF-βin follicular epithelial cell were not same. The expression of VEGF enhanced continuously with the progression of the disease. While The expression of TGF-βchanged little in GD and HT. But both positive expression also appears suggested their common function in vasiformation.2. The expression of CD20 and CD45RO were similar in all subtypes in GD and HT, this suggested proliferation of infiltrating lymphocytes were polyclone. They express simultaneously suggested the coexist of humoral immunity and cell immunity in AITD.3. The aggregate analysis of VEGF,TGF-β,CD20 and CD45RO was very important to clinic for diagnosing, treating and evaluating prognosis of GD and HT. Their function in GD and HT and the relationship of them need further research.