Lei Zhao1, Di Teng1, Xiaoguang Shi1, Yongze Li1, Jianming Ba2, Bing Chen3, Jianling Du4, Lanjie He5, Xiaoyang Lai6, Yanbo Li7, Haiyi Chi8, Eryuan Liao9, Chao Liu10, Libin Liu11, Guijun Qin12, Yingfen Qin13, Huibiao Quan14, Bingyin Shi15, Hui Sun16, Xulei Tang17, Nanwei Tong18, Guixia Wang19, Jin-An Zhang20, Youmin Wang21, Yuanming Xue22, Li Yan23, Jing Yang24, Lihui Yang25, Yongli Yao26, Zhen Ye27, Qiao Zhang28, Lihui Zhang29, Jun Zhu30, Mei Zhu31, Zhongyan Shan1, Weiping Teng1. 1. Department of Endocrinology and Metabolism and The Institute of Endocrinology, The First Hospital of China Medical University, Shenyang, P.R. China. 2. Department of Endocrinology, Chinese PLA General Hospital, Beijing, P.R. China. 3. Department of Endocrinology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China. 4. Department of Endocrinology, The First Affiliated Hospital of Dalian Medical University, Dalian, P.R. China. 5. Department of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital of Ningxia Medical University, Yinchuan, P.R. China. 6. Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Nanchang University, Nanchang, P.R. China. 7. Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China. 8. Department of Endocrinology, Hohhot First Hospital, Hohhot, P.R. China. 9. Department of Endocrinology and Metabolism, The Second Xiangya Hospital, Central South University, Changsha, P.R. China. 10. Research Center of Endocrine and Metabolic Diseases, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, P.R. China. 11. Department of Endocrinology and Metabolism, Fujian Institute of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, P.R. China. 12. Division of Endocrinology, Department of Internal Medicine, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, P.R. China. 13. Department of Endocrine, First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China. 14. Department of Endocrinology, Hainan General Hospital, Haikou, P.R. China. 15. Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, P.R. China. 16. Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China. 17. Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, P.R. China. 18. Department of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, P.R. China. 19. Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, P.R. China. 20. Department of Endocrinology, Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital, Shanghai, P.R. China. 21. Department of Endocrinology, The First Hospital of An Hui Medical University, Hefei, P.R. China. 22. Department of Endocrinology, The First People's Hospital of Yunnan Province, Kunming, P.R. China. 23. Department of Endocrinology and Metabolism, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, P.R. China. 24. Department of Endocrinology, The First Hospital of Shanxi Medical University, Taiyuan, P.R. China. 25. Department of Endocrinology and Metabolism, People's Hospital of Tibet Autonomous Region, Lhasa, P.R. China. 26. Department of Endocrinology, Qinghai Provincial People's Hospital, Xining, P.R. China. 27. Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, P.R. China. 28. Department of Endocrinology and Metabolism, Affiliated Hospital of Guiyang Medical University, Guiyang, P.R. China. 29. Department of Endocrinology, Second Hospital of Hebei Medical University, Shijiazhuang, P.R. China. 30. Department of Endocrinology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, P.R. China. 31. Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, P.R. China.
Abstract
Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, p-value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%, p < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Conclusions: Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.
Background: Subclinical hypothyroidism is diagnosed based on serum thyrotropin (TSH) reference intervals, which in turn are affected by many factors. Methods: Data were acquired from a Chinese nationally representative cross-sectional study of 78,470 participants (TIDE study). The total study population were participants from the TIDE program, and the reference population was a subset of the total population defined by the National Academy of Clinical Biochemistry (NACB) guidelines. Serum concentrations of thyroid hormones, TSH, thyroid antibodies, and urine iodine concentration (UIC) were measured. Results: The geometric mean serum TSH (2.5th-97.5th) for the reference population (defined by the NACB) and total population was 2.28 mIU/L (0.74-7.04 mIU/L) and 2.34 mIU/L (0.61-8.33 mIU/L), respectively. In the reference population, increase in UIC was significantly associated with increase in the 50th and 97.5th centiles and decrease in the 2.5th centile of TSH. The median TSH was significantly higher in women than in men (2.41 mIU/L vs. 2.16 mIU/L, p-value <0.001). Increased age was significantly associated with an increased TSH, 97.5th centile. For each 10-year increase in the population age, the TSH 97.5th centile increased by 0.534 mIU/L. The prevalence of subclinical hypothyroidism diagnosed according to the assay-recommended interval (Roche 0.27-4.2 mIU/L) and NACB standard interval in the TIDE study (0.74-7.04 mIU/L) differed significantly (Roche 13.61% vs. TIDE 3.00%, p < 0.05). However, there was no significant difference in future cardiovascular disease, reflected by the Framingham risk score, between the 0.27-4.2 and 4.2-7.04 mIU/L TSH groups. Conclusions: Serum TSH concentration significantly increased with increase in iodine intake. Thus, iodine intake must be considered in establishing TSH reference intervals. To avoid overdiagnosis and overtreatment of subclinical hypothyroidism, different areas should use individual serum TSH reference intervals.