Establishment of reference interval for thyroid-stimulating hormone using electrochemiluminescence assay in a healthy adult population from Fortaleza, Brazil

Abstract

Objective: This study aimed to determine the thyroid-stimulating hormone (TSH) reference interval (RI) and to assess the influence of the use of thyroid ultrasonography (TUS) on reference individual selection from a healthy adult population in Fortaleza, Brazil. Subjects and methods: This crosssectional study recruited patients (N = 272; age = 18-50 years) with normal thyroid function (NTF) and placed them in three groups according to their test results: NTF (n = 272; all participants), TUS (n = 170; participants who underwent thyroid US), RI (n = 124; reference individuals with normal TSH levels). TSH, FT4, TT3, TgAb, and TPOAb concentrations were determined by electrochemiluminescence assay. TUS was performed using a 7-12 MHz multifrequency linear transducer by two radiologists. The 2.5 th and 97.5 th percentiles of the distribution curve corresponded to lower and upper TSH RI levels, respectively. Results: The mean TSH level was 1.74 ± 0.96 mIU/L, and TSH range was 0.56-4.45 mIU/L. There was no difference in the TSH concentrations between men and women nor between the groups. TUS did not appear to be an essential tool for the reference group selection. Conclusion: The upper limit of TSH was comparable to the reference interval provided by the assay manufacturer (4.45 vs. 4.20 mIU/L) but the lower limit was not (0.56 vs. 0.27 mIU/L). This finding may have a clinical impact since these values may lead to the misdiagnosis of euthyroid patients with subclinical hyperthyroidism.

Reference intervals for thyroid disorders calculated by indirect method and comparison with reference change values

“…Table 4 shows the variabilities of studies in literature: different analysers, different populations, study type, statistical calculations (21, 22). As a result, LRLs of the studies vary between 0.17-0.75 mIU/L and URLs between 2.84-5.32 mIU/L for TSH; even 4 studies on the same platform (Roche) like ours, LRLs and URLs vary between 0.43-0.75 and 3.93-5.32 mIU/L, respectively ( 5 , 7 , 8 , 18 ). Our TSH RI was found in the middle of this range.…”

“…Another point is the thyroid ultrasonography (TUS) evaluation for the selection of reference individuals. In our study and other indirect studies this was not possible, however, TUS is not recommended in even strict NACB guidelines since it is not proven to be associated with TSH RIs in some studies (7). However, if patient selection could be made together with TUS results, it would contribute to the selection of reference individuals; so this may be the considered as the weakness of the study.…”

“…Discrepancies were also observed when studies were grouped as direct and indirect RI calculation methods. LRLs were 0.56 and 0.75 mIU/L; URLs were 4.45 and 5.32 mIU/L with two direct methods on the same analyser ( 7 , 8 ). Thus, differences between RIs in the medical studies were hard to attribute to any variable.…”

“…fT3 -free triiodothyronine. the same analyser (7,8). Thus, differences between RIs in the medical studies were hard to attribute to any variable.…”

“…But there are still discrepancies between RIs used in laboratories as well as up-to-date scientific literature (1). In recent studies, calculated thyroid stimulating hormone (TSH) upper limits varied between 5.28 to 2.84 mIU/L and lower limits from 0.17 to 0.64 mIU/L with remarkable differences in RIs of free triiodothyronine (fT3) and free thyroxine (fT4) too (7)(8)(9)(10). Variations in the results of thyroid function tests in a healthy population may be due to analytical (CV A ), intra-individual (CV İ ) and inter-individual (CV G ) variations.…”