Comparison on the consistency of Mindray and Siemens chemiluminescence analyzers for detecting FT3, FT4 and TSH in patients with hyper- and hypothyroidism
Introduction
The human thyroid gland, which is located at the base of the neck and wraps around the trachea just below the cricoid cartilage (1,2), is a very important endocrine organ, responsible for secreting thyroid hormones to maintain normal functioning of the body. Thyroxine (T4) and triiodothyronine (T3) play extremely important roles in protein synthesis, temperature regulation, and energy generation and regulation (3-5). Part of the T3 and T4 synthesized by and secreted from the thyroid gland combines with protein in the blood and is preserved temporarily, and the rest circulates as free forms known as FT3 and FT4, which are ready at any time to play their roles (6,7). When FT3 and FT4 are consumed, the combined T3 and T4 will separate into FT3 and FT4 for timely supplementation. Interaction of the pituitary and hypothalamus with the thyroid gland causes the production and release thyroid stimulating hormone (TSH) and thyrotropin-releasing hormone respectively to maintain the blood levels of thyroid hormones within the normal range (8,9). Thyroid function abnormalities mainly include hyperthyroidism and hypothyroidism (10).
Clinically, thyroid function is usually assessed by the circulating levels of FT3, FT4 and TSH. In hypothyroidism, there is negative feedback from FT3 and FT4 to secrete more TSH, leading to elevated TSH level, whereas in hyperthyroidism, FT3 and FT4 levels are generally elevated, causing a reduction in the TSH level (11-14). Subclinical hypothyroidism/hyperthyroidism presents either no or unclear clinical symptoms, and the FT3 and FT4 levels are usually within the normal range (15-17). However, the TSH level in subclinical hypothyroidism is usually higher than normal, and in subclinical hyperthyroidism it is usually lower than normal (18,19). The routine combination of TSH with FT3 and FT4 is widely used to monitor thyroid function and establish the etiology to better guide clinical decision making (20,21).
With the rapid development of laboratory medicine in recent years, various test instruments are available for use in laboratory medicine departments of hospitals, and the same department may even use two or more test instruments for the same purpose (22). In addition, several chemiluminescence detection systems on the market, but the detecting results can vary significantly between different detection systems, which would produce unreliable results. Moreover, inconsistency of measurement results between different detection systems could affect clinical judgment. This makes it necessary to compare the test results of different instruments to ensure that the deviation between them is within the clinically acceptable range. The aim of the present study was to compare the test results of FT3, FT4 and TSH between the Mindray and Siemens full-automatic chemiluminescence analyzers, including the attached reagents, to assess the consistency and compatibility of different test systems, as well as provide a reference for selecting appropriate test instruments for clinical use. We present the following article in accordance with the STARD reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4589/rc).
Methods
General data
Included in this study were 107 patients with primary hyperthyroidism and 57 patients with primary hypothyroidism who were diagnosed at Nang Fang Hospital of Southern Medical University (Guangzhou, China) between January and December 2021 (75 males, 89 females; age range 18–55 years). An additional 100 healthy subjects who underwent routine health examination at the outpatient department of the same hospital with normal routine test results without definite thyroid-related diseases were used as the control group. All samples were nonhemolytic with no severe lipid turbidity and with a sufficient volume of serum. This study was approved by the Ethics Committee of Nang Fang Hospital of Southern Medical University (No. NFEC-2020-235), and written informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Instruments and reagents
The instruments and reagents used in this study were the Mindray full-automatic chemiluminescence analyzer (CL6000i) including the FT3, FT4 and TSH reagent kits and calibrators, and the Siemens full-automatic chemiluminescence analyzer (ADVIA Centaur XP) including the FT3, FT4 and TSH reagent kits and calibrators. Each sample was tested according to the manufacturer’s instructions with supplied reagents and the results were analyzed statistically.
Evaluation criteria for FT3, FT4 and TSH testing
The clinical or ultrasonograph examinations were used to diagnose the hyperthyroidism and hypothyroidism. In addition, two chemiluminescence analyzers were carried out to detect the level of FT3, FT4 and TSH and the evaluation criteria for FT3, FT4 and TSH are shown in Table 1.
Table 1
| Result judgment | Siemens | Mindray | |||||
|---|---|---|---|---|---|---|---|
| FT3 (pmol/L) | FT4 (pmol/L) | TSH (μIU/mL) | FT3 (pmol/L) | FT4 (pmol/L) | TSH (μIU/mL) | ||
| Negative | 3.52–6.43 | 11.50–22.70 | 0.35–5.5 | 2.76–6.45 | 11.20–23.81 | 0.35–5.1 | |
| Hyperthyroidism | ≥6.43 | ≥22.70 | ≤0.35 | ≥6.45 | ≥23.81 | ≤0.35 | |
| Hypothyroidism | ≤3.52 | ≤11.50 | ≥5.5 | ≤2.76 | ≤11.20 | ≥5.1 | |
The result judgment was supplied by the manufacturer in the instructions. FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
Statistical analysis
The test results were compared with the reference ranges of the test kits to analyze values lower than the reference range, higher than the reference range and within the reference range using SPSS 20.0 and Medcalc 15.0 software. The test results are expressed as the mean ± standard deviation. Comparison between two groups was conducted by t test. Relative coefficient (R2) was calculated by linear regression analysis. Result consistency was verified by kappa test. The degree of consistency was divided into 5 sections: Kappa 0.81–1.0, extremely strong consistency; Kappa 0.61–0.8, high consistency; Kappa 0.41–0.6, moderate consistency; Kappa 0.21–0.4, weak consistency; Kappa 0–0.2, very weak consistency (23). Consistency was also evaluated by Bland-Altman analysis, with the mean of the two systems of detection as the x-axis and the difference as the y-axis. The diagnostic efficacy was judged by receiver operating characteristic (ROC) and area under the curve (AUC). P<0.05 was considered significantly different.
Results and discussion
Test results of FT3, FT4 and TSH from the two instruments
The levels of FT3, FT4 and TSH in the two patient groups and the controls by the Mindray system are shown in Table 2. The hyperthyroidism patients had significantly increased FT3 and FT4 levels and significantly decreased TSH levels compared with the normal control group (t value =12.97, 11.15 and 20.06 respectively, P<0.05). The hypothyroidism patients had significantly decreased levels of FT3 and FT4 and significantly increased TSH compared with the control group (t value =9.48, 12.36 and 6.43 respectively, P<0.05).
Table 2
| Group | n | FT3 (pmol/L) | FT4 (pmol/L) | TSH (μIU/mL) |
|---|---|---|---|---|
| Control | 100 | 4.40±0.45 | 19.31±2.00 | 2.12±1.04 |
| Hyperthyroidism | 107 | 10.75±5.04 | 39.05±18.20 | 0.03±0.07 |
| t | 12.97 | 11.15 | 20.06 | |
| P | <0.0001 | <0.0001 | <0.0001 | |
| Hypothyroidism | 57 | 3.26±0.84 | 12.64±3.78 | 22.05±23.38 |
| t | 9.48 | 12.36 | 6.43 | |
| P | <0.0001 | <0.0001 | <0.0001 |
The data are expressed as the mean ± standard deviation. FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
The test results for FT3, FT4 and TSH in the control, hyperthyroidism and hypothyroidism groups by Siemens are shown in Table 3. The hyperthyroidism patients had significantly increased levels of FT3 and FT4 and significantly decreased level of TSH (t value =11.87, 12.06 and 19.34 respectively, P<0.05). The hypothyroidism patients had significantly decreased levels of FT3 and FT4 and significantly increased TSH (t value =9.57, 13.87 and 6.71 respectively P<0.05). The results indicated that both the Mindray and Siemens systems could provide references for relevant clinical evaluation. Therefore, we further examined the consistency of the results obtained by the two systems.
Table 3
| Group | n | FT3 (pmol/L) | FT4 (pmol/L) | TSH (μIU/mL) |
|---|---|---|---|---|
| Control | 100 | 5.00±0.5 | 16.97±1.72 | 1.82±0.90 |
| Hyperthyroidism | 107 | 11.89±5.92 | 31.45±12.29 | 0.02±0.06 |
| t | 11.87 | 12.06 | 19.34 | |
| P | <0.0001 | <0.0001 | <0.0001 | |
| Hypothyroidism | 57 | 3.79±0.88 | 11.44±2.72 | 17.79±17.95 |
| t | 9.57 | 13.87 | 6.71 | |
| P | <0.0001 | <0.0001 | <0.0001 |
The data are expressed as the mean ± standard deviation. FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
Consistency of the two systems in detecting FT3, FT4 and TSH
The Kappa values of serum FT3, FT4 and TSH in the normal control subjects and hyperthyroidism patients using the two test systems were 0.798, 0.921 and 0.795 respectively (Table 4), showing good consistency between the two test systems. The respective Kappa values of serum FT3, FT4 and TSH in the normal control subjects and hypothyroidism patients were 0.925, 0.860 and 0.913 (Table 5), also showing good consistency between the two test systems.
Table 4
| Index | Siemens | Mindray | Kappa | Degree of consistency | |
|---|---|---|---|---|---|
| Positive (n) | Negative (n) | ||||
| FT3 | Positive | 82 | 7 | 0.798 | High |
| Negative | 0 | 18 | |||
| FT4 | Positive | 81 | 0 | 0.921 | Extremely strong |
| Negative | 3 | 23 | |||
| TSH | Positive | 104 | 2 | 0.795 | High |
| Negative | 0 | 1 | |||
FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
Table 5
| Index | Siemens | Mindray | Kappa | Degree of consistency | |
|---|---|---|---|---|---|
| Positive (n) | Negative (n) | ||||
| FT3 | Positive | 20 | 2 | 0.925 | Extremely high |
| Negative | 0 | 35 | |||
| FT4 | Positive | 26 | 4 | 0.860 | High |
| Negative | 0 | 27 | |||
| TSH | Positive | 50 | 0 | 0.913 | Extremely strong |
| Negative | 6 | 1 | |||
FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
Linear correlation and regression analyses of FT3, FT4 and TSH between the two systems
Using test results obtained by Siemens as the comparison method (X) and those by Mindray as (Y), scatter-plot analysis of FT3, FT4 and TSH was performed. Figure 1 shows there was a good linear correlation between Siemens and Mindray in detecting FT3, FT4 and TSH in hyperthyroidism samples. Figure 2 shows the two test methods had a good linear correlation in detecting FT3, FT4 and TSH of hypothyroidism patients. In summary, the comparative results for Siemens and Mindray were clinically acceptable, and the results from the two systems were highly consistent.
Deviation of the two systems in detecting FT3, FT4 and TSH
The test results obtained for the patients were analyzed by the Bland-Altman method. For the hyperthyroid group, the mean difference value of the two systems in detecting FT3 was 1.1 pmol/L [95% confidence interval (CI): 0.8–1.3], 6.5% (7/107) was outside the consistency boundary, and the maximum difference/mean value ratio was 31.4% (3.55/11.29) within the boundary (Figure 3A); the mean difference value of FT4 was −7.6 pmol/L (95% CI: −8.9 to −6.3), and 3.7% (4/107) was outside the consistency boundary (Figure 3B). The mean difference value of TSH was −0.01 µIU/mL (95% CI: −0.014 to −0.007), and 6.5% (7/107) was outside the consistency boundary (Figure 3C). These results showed that the two systems had good consistency in detecting FT3, FT4 and TSH in hyperthyroidism patients.
In the hypothyroid group for FT3 the mean difference value of the two systems outside the consistency boundary was 3.5% (2/57), and the maximum difference value to the mean value ratio was 23.6% (0.83/3.52) (Figure 4A). The mean difference value of FT4 was −1.2 pmol/L (95% CI: −1.56 to −0.85), and 1.8% (1/57) was outside the consistency boundary (Figure 4B). In addition, the mean difference value of TSH was −4.3 µIU/mL (95% CI: −5.83 to −2.69), and 5.3% (3/57) was outside the consistency boundary (Figure 4C). These results showed that the detection difference between the two system in detecting FT3, FT4 and TSH in hypothyroid patients was within the acceptable range. In summary, the two detection systems had good consistency and their detection results could clinically replace each other.
Comparison of ROC curves between the two systems
The results obtained for the hyperthyroidism patients were analyzed by ROC. As shown in Figure 5 and Table 6, the AUC of Siemens was almost the same as that of Mindray for FT3, FT4 and TSH. In addition, there was no significant difference among the three indexes (all P>0.05). Under the corresponding criterion concentration (Table 6), the specificity of all the indexes was 100%, and there was no significant difference in sensitivity, either. We confirmed that the two detection systems had good diagnostic efficacy for hyperthyroidism.
Table 6
| Index | System | AUC | P value | Criterion | Sensitivity% | Specificity% |
|---|---|---|---|---|---|---|
| FT3 | Siemens | 0.9449 | P=0.6985>0.05 | >6.33 (pmol/L) | 81.72 | 100 |
| Mindray | 0.9440 | >5.41 (pmol/L) | 90.65 | 100 | ||
| FT4 | Siemens | 0.9289 | P=0.9321>0.05 | >21.11 (pmol/L) | 83.18 | 100 |
| Mindray | 0.9279 | >23.56 (pmol/L) | 78.50 | 100 | ||
| TSH | Siemens | 0.9999 | P=0.9989>0.05 | ≤0.27 (μIU/mL) | 99.07 | 100 |
| Mindray | 0.9999 | ≤0.343 (μIU/mL) | 99.07 | 100 |
AUC, area under the curve of receiver operating characteristic (ROC); FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
The results for the hypothyroidism patients were also analyzed by ROC. As shown in Figure 6 and Table 7, the AUC of the two systems was almost the same for FT3, FT4 and TSH. In addition, there was no significant difference among the three indexes (all P>0.05). Under the corresponding criterion concentration (Table 7), there was a slight difference in sensitivity and specificity between the two systems, but the difference was within the acceptable range, suggesting that the two detection systems had good diagnostic efficacy for hypothyroidism.
Table 7
| Index | System | AUC | P value | criterion | Sensitivity% | Specificity% |
|---|---|---|---|---|---|---|
| FT3 | Siemens | 0.8882 | P=0.8559>0.05 | ≤4.42 (pmol/L) | 80.70 | 89 |
| Mindray | 0.8865 | ≤3.78 (pmol/L) | 73.68 | 92 | ||
| FT4 | Siemens | 0.9676 | P=0.0723>0.05 | ≤13.77 (pmol/L) | 87.50 | 98 |
| Mindray | 0.9534 | ≤16.73 (pmol/L) | 92.86 | 87 | ||
| TSH | Siemens | 0.9998 | P=0.2397>0.05 | >4.73 (μIU/mL) | 100 | 99 |
| Mindray | 0.9981 | >5.30 (μIU/mL) | 98.23 | 99 |
AUC, area under the curve of receiver operating characteristic (ROC); FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyroid stimulating hormone.
Conclusions
In the present study, we systematic analyzed the consistency of the Siemens and Mindray systems in detecting FT3, FT4 and TSH in both hyper- and hypothyroidism patients by using Kappa, linear regression, Bland-Altman consistency and ROC analyses. The results showed that the two systems were highly consistent in detecting FT3, FT4 and TSH, and the deviation was within the acceptable range. To the best of our knowledge, there is no consensus criterion for judging clinical acceptability. The present study may promote mutual authentication of the results of different test systems, thus reducing both the complaint of clinical departments or patients about the inconsistency of test results from different laboratories or the same laboratory, and the psychological and economic burden arising from repeated laboratory tests. However, the consistency of Siemens and Mindray with other chemiluminescence detection systems needs to be further studied and confirmed by multicenter clinical trials.
Acknowledgments
Funding: This study was supported by Guangdong Province Key Field R&D Program Project (No. 2020B1111160001), and Guangdong Basic and Applied Basic Research Foundation (No. 2021A1515110821).
Footnote
Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-22-4589/rc
Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-4589/dss
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4589/coif). HZ and GS are from Shenzhen Mindray Bio-Medical Electronics Co., Ltd. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the Ethics Committee of Nang Fang Hospital of Southern Medical University (No. NFEC-2020-235), and written informed consent was obtained from all patients. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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(English Language Editor: K. Brown)
