A multicenter study for the evaluation of the reference interval for TSH in Italy (ELAS TSH Italian Study)

Abstract

Background The aims of this study were: (1) to calculate reliable thyroid stimulating hormone (TSH) reference intervals using laboratory databases; (2) to evaluate the relationship between TSH, sex and age values in different large Italian populations. Methods The TSH values stored in the laboratory information system of clinical laboratories of four Italian city hospitals, including 146,801 TSH measurements (with the respective age and sex data of individuals) were taken in consideration. Assuming a log-normal distribution, to log-transformed TSH values were applied the Dixon's iterative principle in order to exclude the outliers. At the end of this iterative process 142,821 log-transformed TSH results remained. The four clinical laboratories measured serum TSH concentrations using the same TSH immunoassay method (Access TSH 3rd IS, using UniCel DxI platform). Results The TSH reference interval calculated in the present study (0.362-5.280 mIU/L) is similar to that suggested by the manufacturer for the Access TSH 3rd IS assay (0.45-5.33 mIU/L). TSH values in females were significantly higher than in males (females: mean=2.06 mIU/L; standard deviation [SD]=1.26 mIU/L; n=101,243; males: mean=1.92 mIU/L; SD=1.19 mIU/L; n=41,578; p<0.0001). Moreover, a negative linear relationship was observed between TSH throughout all interval age values (from 0 to 105 years). Conclusions The results of the present multicenter study confirm that data mining techniques can be used to calculate clinically useful reference intervals for TSH. From a pathophysiological point of view, our results suggest that some Northern populations of Italy might still suffer some harmful effects on the thyroid gland due to mild to moderate iodine intake deficiency. Specific clinical trials are needed to confirm these results.

Reference intervals for thyroid‐stimulating hormone and thyroid hormones using the access TSH 3rd IS method in China

“…The reference intervals suggested by manufacturer for TSH (0.49‐4.91 mIU/L), FT4 (0.59‐1.25 ng/dL), FT3 (2.14‐4.21 pg/mL), TT4 (5.44‐11.85 μg/dL), and TT3 (0.66‐1.61 ng/mL) were calculated on a general population (n = 1316) of approximately equal numbers of male and female individuals with ages ranging from 18 to 86 years. Previously, the reference interval for TSH using new Access TSH 3rd IS assay was also verified in Italian populations, which was 0.362‐5.280 mIU/L . The reference interval in Italian populations is similar to that suggested by the manufacturer.…”

“…We only found that the levels of FT3 in subjects with the age of less than 30 years were significantly higher than other groups. However, according to Clerico et al, a negative linear relationship was observed between TSH throughout all interval age values and TSH values in Italian populations tend to decrease with age. These conflicting results may be explained by taking into account the different pathophysiological conditions of the enrolled individuals and the large difference between sample sizes.…”

“…These conflicting results may be explained by taking into account the different pathophysiological conditions of the enrolled individuals and the large difference between sample sizes. Given that TSH is a kind of labile hormone, only a single determination may be a unreliable representative of long‐term thyroid status, especially in clinical studies including a relatively low number of individuals . Therefore, clinical and demographic characteristics of included subjects may strongly affect the results of studies concerning the distribution of TSH values in reference populations.…”

“…However, the available reference intervals for TSH and other thyroid hormones are established in western populations . It is well known that there is significant variability between different populations, making it inappropriate to use values derived for one population to evaluate another populations . Ideally, there should be a reference interval derived from a representative cohort of healthy subjects in Chinese populations.…”

Indirect Reference Intervals: Harnessing the Power of Stored Laboratory Data

“…This may simply involve excluding values beyond an arbitrary limit, such as those more than 10 times the upper reference limit 13 or involve a statistical test, such as that of Tukey, or others. [14][15][16] Another data pre-processing step that may be used is the exclusion of data from particular referral sites where there is a high likelihood that the patients have significant disease, such as intensive care units and oncology departments. 13,17 It may also be appropriate to exclude data from additional referral sites depending on the analyte of interest, for example lipid and renal clinics.…”