Factors Influencing the Reference Interval of Thyroid Stimulating Hormone in Healthy Adults: A Systematic Review and Meta-analysis

Abstract Background: Thyroid stimulating hormone (TSH) is an important indicator for evaluating thyroid function. Many studies have reported that the TSH reference interval is susceptible to external factors. This paper summarizes the related studies published in recent years and comprehensively analyzes the effects of these factors on the TSH reference interval in healthy people.Methods: Articles published from January 1980 to January 2020 were searched in PubMed, EMBASE, Cochrane, Scopus, Medline English databases and CNKI, WanFang and CQVIP Chinese databases. In total, 21 studies were ultimately included. All data were analyzed using Review Manager 5.3 software and STATA 16.0 software. Microsoft Excel 2010 was used to draw the TSH concentration curve changing with age, and GraphPad 6.0 was used to draw the TSH concentration curve with sex.Results: The TSH reference interval was significantly influenced by sex and age. The overall trend of TSH concentration reveals that males are lower than females. The TSH reference interval is divided into 20~59-year-old, 60~69-year-old and over 70-year-old age groups for males and 20~39-year-old, 40~49-year-old, 50~69-year-old and over 70-year-old age groups for females. Regardless of sex, TSH concentrations all increase with age. In iodine-deficient areas, TSH reference intervals are generally lower than those in iodine-sufficient or iodine-excessive areas. The TSH reference interval in Asia and North American countries is generally higher than that in most European countries. Even the detection methods are consistent, different detection instruments can affect the TSH reference interval. Sample size and race are also important factors.Conclusion: The TSH reference interval was significantly influenced by sex and age, race, region, iodine intake, sample size, detection instruments and methods, 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.