Factors influencing the reference interval of thyroid-stimulating hormone in healthy adults: A systematic review and meta-analysis

Background Many studies have reported that the thyroid-stimulating hormone (TSH) reference interval is susceptible to external factors, such as age, sex, race, region and iodine intake. However, no meta-analysis has comprehensively explored the effect of these factors on the TSH reference interval. Methods Articles published from January 1960 to January 2020 were searched in PubMed, Embase, Cochrane, Scopus, Medline English databases and CNKI, WanFang and CQVIP Chinese databases. In total, 19 studies were ultimately included. All data were analysed using Review Manager 5.3, STATA 16.0 software, GraphPad Prism 8.0 and Microsoft Excel 2010 to draw the TSH concentration curve. Results The TSH reference interval was significantly influenced by sex and age. The mean of TSH concentration in females was 0.27 mIU/L higher than that in males. Reference interval of TSH is divided into 20-59 years old and >60 years old age groups in males, and 20-39 years old and >40 years old age groups in females. Regardless of sex, TSH concentrations all increase with age. In iodine-deficient areas, TSH reference intervals were generally lower than those in iodine-sufficient or iodine-excessive areas. The TSH reference interval in Asia and North American countries was generally higher than that in most European countries. In the subgroup analyses of sample size, region and assay methods and manufacturers, the between-group differences were significant. Conclusion The TSH reference interval was significantly influenced by sex, age, iodine intake, sample size, region, and assay methods and manufacturers, but other factors should not be ignored. Therefore, it is necessary for each laboratory to validate an appropriate TSH reference interval based on local conditions.