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ORIGINAL ARTICLE
Year : 2017  |  Volume : 14  |  Issue : 3  |  Page : 118-121

Evaluating thyroid function in the clinical laboratory


Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica

Date of Web Publication9-Oct-2017

Correspondence Address:
Donovan A McGrowder
Department of Pathology, University of the West Indies, Mona, Kingston 7
Jamaica
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/trp.trp_9_17

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  Abstract 

Background: Thyroid disorders are common in clinical medicine and laboratory confirmation is essential, especially in cases where overt signs and symptoms are absent. The measurement of thyroid-stimulating hormone (TSH) is recommended as the best indicator of thyroid function and is utilized along with thyroxine (T4) and in some circumstances triiodothyronine (T3).
Aim: The aim is to evaluate the relationship between TSH and free T4 (FT4), and TSH and FT3.
Methods: Thyroid function tests (TFTs) – TSH, FT4, and FT3 – performed in the Chemical pathology laboratory from February to December 2015 were retrieved from the laboratory information management system. Results were classified based on TSH results into suppressed, mildly suppressed, normal, mildly elevated and elevated, and correlated with FT3 and FT4 results. Results were also categorized as overt hyperthyroidism, subclinical hyperthyroidism, normal, subclinical hypothyroidism, overt hypothyroidism, and “others” and compared based on age and gender.
Results: FT4 and FT3 correlate best with TSH at suppressed and elevated levels. Mean TSH was significantly higher in males than in females only in those with normal FT4 and TSH. TSH was significantly higher in the 41–60 age group, with females in this group having significantly higher levels as compared to males.
Conclusions: There is an inverse correlation between FT4 and TSH, and FT3 and TSH, especially significant at suppressed and elevated levels of TSH. Highest TSH levels were observed in women in the 41–60 age cohort.

Keywords: Hyperthyroidism, hypothyroidism, thyroid stimulating hormone, thyroxine, tri-iodothyronine


How to cite this article:
Tapper MA, Francis CA, Dilworth LL, McGrowder DA. Evaluating thyroid function in the clinical laboratory. Thyroid Res Pract 2017;14:118-21

How to cite this URL:
Tapper MA, Francis CA, Dilworth LL, McGrowder DA. Evaluating thyroid function in the clinical laboratory. Thyroid Res Pract [serial online] 2017 [cited 2020 Jun 5];14:118-21. Available from: http://www.thetrp.net/text.asp?2017/14/3/118/216215


  Introduction Top


Thyroid dysfunction is one of the most common medical disorders in clinical practice.[1],[2] Signs and symptoms of the disease can be difficult to elucidate necessitating the use of biochemical tests for diagnosis.[3]

The analysis of thyroid-stimulating hormone (TSH) is the recommended screening test for the identification of primary disease.[1],[2],[4] Together with TSH, free T4 (FT4) is utilized in evaluating thyroid function and monitoring therapy. FT3 is used for diagnosing T3-toxicosis and monitoring treatment of hyperthyroidism.[4],[5]

Thyroid function tests (TFTs) are measured by immunoassays employing enzymes, fluorescent or light-emitting molecules for detection.[5] The third generation TSH assays provide increased diagnostic sensitivity and specificity to accurately identify disorders.[4],[6]


  Methods Top


A review of records in the laboratory information management system (LIMS) was carried out to retrieve results of TFTs done between February and December 2015. All results of patients 18 years and older who had assays done for TSH and FT4 and/or FT3 were included in this study. The assigned data entry numbers from the LIMS were used for identification to maintain confidentiality. No information on diagnosis and treatment was available. Analyses were performed by electrochemiluminescence immunoassay using the cobas 6000 (Roche Diagnostics, Indianapolis, USA) module e601. The methodology for TSH analysis is a two-point sandwich assay while the FT4 assay is a competitive indirect test. Results were classified based on the normal ranges for TFTs are indicated in [Table 1].
Table 1: Ranges for interpretation of thyroid function test results

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The results were subdivided based on TSH levels into five groups: suppressed (<0.1 mU/L), mildly suppressed (0.1–0.4 mU/L), normal (0.4–4 mU/L), mildly elevated (4.01–10 mU/L), and elevated (>10 mU/L). The relationship between TSH and FT3 and between TSH and FT4 was analyzed using the Pearson correlation coefficient.

Patients were categorized by FT4 and TSH results as overt hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, overt hyperthyroidism, and others and additionally with FT3 results to identify T3 toxicosis, as indicated in [Table 2]. Relationships of TSH and FT4 results were evaluated by gender and age. The data analysis was conducted using the IBM Statistical Programme of the Social Science version 22 (IBM Corporation, Armonk, N.Y. USA) and Microsoft Excel (Microsoft Corporation, Redmond, W.A. USA).
Table 2: Characterization of thyroid disorders based on thyroid function test results

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  Results Top


A total of 2877 TSH results were retrieved along with 2864 FT4 and 1107 FT3 results for analysis. There were 2061 (72%) female and 816 (28%) male with TSH results. The majority of patients (2237 or 77.8%) had TSH within the reference interval [Figure 1].
Figure 1: Distribution of results by thyroid-stimulating hormone levels

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In patients with suppressed TSH, the average FT3 was elevated (7.46 pg/mL) showing the most significant inverse relationship. The average FT3 for patients with normal, mildly suppressed, mildly elevated, and elevated TSH was within the reference range. The patients with suppressed TSH also had expected elevated average FT4 (2.17 ng/mL). In the elevated TSH group, the average FT4 was just below the reference interval (0.74 ng/mL). In the remaining groups, the average FT4 was within reference range [Table 3].
Table 3: Mean±standard deviation of free triiodothyronine and free thyroxine by thyroid-stimulating hormone levels

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The subset of patients that showed the best correlation between TSH and FT3 and between TSH and FT4 was the elevated TSH group. Significant correlation was also observed in the suppressed TSH group for both FT3 and FT4. Correlation was also good in the mild suppressed and normal groups for FT4 (P = 0.024 and P = 0.002, respectively) while in the mild elevated group correlation was better with FT3 (P = 0.037 vs. P =0.089) [Table 4].
Table 4: Correlation of free triiodothyronine and free thyroxine by thyroid-stimulating hormone levels

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The patients categorized as overt hypothyroidism, subclinical hypothyroidism, normal, subclinical hyperthyroidism, overt hyperthyroidism and “others” are indicated in [Table 5]. “Others” included those with high FT4 and normal TSH,[1] low FT4 and normal TSH,[2] and normal FT4 and elevated TSH (>10.0 mU/L),[3] and results suggestive of central hypothyroidism,[4] FT4 low and TSH low. There were no patients with results characteristic of central (TSH dependent) hyperthyroidism (FT4 high and TSH high) [Table 5].
Table 5: Thyroid function tests of subjects by gender

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A number of tests done for female were significantly higher than those for male. In all categories suggestive of thyroid disorders, the ratio of female to male was >2:1 [Table 5].

Within reference limits of FT4 and TSH, male had significantly higher levels of TSH (P< 0.05) [Table 6].
Table 6: Relationship between free thyroxine and thyroid-stimulating hormone by gender

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[Table 7] displays the relationship between TSH and FT4 in the different age groups of individuals with FT4 within the reference limit. There were significant differences in the TSH levels (P< 0.001), with patients in the 41–60 group exhibiting higher mean levels of TSH overall. Female in the 41–60 age group had significantly higher levels (P< 0.05) of TSH compared to other age groups. The differences observed in male were not significant but higher mean levels were revealed in the ≥61 age group.
Table 7: Thyroid stimulating hormone in subjects with normal free thyroxine levels by age groups

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  Discussion Top


Thyroid hormone production is regulated by a negative feedback mechanism; as TH levels rise, TSH levels fall and vice versa, hence there is a negative correlation between FT4 and TSH, and FT3 and TSH. The relationship is more significant in the hypothyroid and hyperthyroid states as observed from results of the collected data. Verghese et al. reported significant correlation in hypothyroid patients, especially when TSH levels were highest, and in hyperthyroid individuals, when TSH values were lowest.[7] Many studies have been conducted looking at the log-linear relationship between TSH and FT4 with the more recent showing nonlinearity but significant inverse correlation. Hadlow et al.,[8] in a large study, reported significant negative correlation and nonlinearity while Hoermann et al.[9] and Clark et al.[10] reported similar results in smaller studies. The study did not examine the relationship in terms of linearity. However, inverse correlation was observed by Pearson coefficient.

Overall there was no statistically significant difference in FT4 and TSH values between female and male; although, there was significant difference noted in euthyroid individuals. Higher (but nonsignificant) levels in male were otherwise only observed in those with high FT4 levels (P = 0.106). Hadlow et al. reported significantly higher overall TSH in men most evident in those with higher FT4 levels.[8]

Statistically significant differences were observed in the mean TSH for normal FT4 levels in patients categorized by age groups as shown (P< 0.001). Higher mean values were obtained for the 41–60 age group overall. In contrast, several cross-sectional studies reported higher mean TSH as age increased with highest levels seen with the oldest patients.[8],[11],[12],[13] When sorted by gender female had significantly higher levels in the 41–60 age group whereas in male the mean difference in TSH was not statistically significant. However, higher mean values were noted in the ≥61 age group.

The number of female compared to male in the study indicates the difference in TFTs requested for female reflecting the fact that women are more likely to be diagnosed with thyroid disorder. As expected, a higher prevalence of thyroid disorders is observed in women than men.

A limitation of the study was the unavailability of clinical information on the patients. Therefore, results were not classified to reflect actual but suggested status. Results suggesting euthyroidism may not only reflect normal patients but those being successfully treated for thyroid disease states. Discordant FT4/TSH results may indicate poor compliance, nonachievement of steady state with treatment or nonthyroidal illness. Results are also affected by conditions such as pregnancy, medications, smoking, and factors which alter assay specificity including the presence of heterophile antibodies in serum.[4] The sample size is also a limitation and could have yielded different results had the numbers of hypothyroid and hyperthyroid patients been higher.


  Conclusions Top


TSH levels are inversely correlated with FT4 and FT3 particularly with elevated and suppressed levels of TSH, with better correlation of FT4 in the normal to suppressed groups and of FT3 in the mildly elevated and elevated groups. The prevalence of thyroid disorders is higher in female than male. Mean TSH levels were found to be higher in middle-aged patients who are female. Secondary hyperthyroidism is uncommon in our population.

Acknowledgment

Sincere gratitude to Mr. Laurel Choy for technical assistance with retrieval of data.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ladenson PW, Singer PA, Ain KB, Bagchi N, Bigos ST, Levy EG, et al. American thyroid association guidelines for detection of thyroid dysfunction. Arch Intern Med 2000;160:1573-5.  Back to cited text no. 1
[PUBMED]    
2.
UK Guidelines for the Use of Thyroid Function Tests. Association of Clinical Biochemistry, British Thyroid Association, British Thyroid Foundation. Available from: http://www.british-thyroid-association.org/TFT_guideline_final_version_July_2006.pdf. [Last accessed on 2017 Jan 06].  Back to cited text no. 2
    
3.
Joshi S. Laboratory evaluation of thyroid function. JAPI 2011;49:14-20.  Back to cited text no. 3
    
4.
Carvalho GA, Perez CL, Ward LS. The clinical use of thyroid function tests. Arq Bras Endocrinol Metabol 2013;57:193-204.  Back to cited text no. 4
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Demers LM, Spencer C. The thyroid: Pathophysiology and thyroid function testing. In: Burtis CA, Bruns DE, Sawyer BG, Tietz NW, editors. Tietz Fundamentals of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis: Elsevier, Saunders; 2006. p. 2053-87.  Back to cited text no. 5
    
6.
Kazerouni F, Amirrasouli H. Performance characteristics of three automated immunoassays for thyroid hormones. Caspian J Intern Med 2012;3:400-104.  Back to cited text no. 6
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7.
Verghese A, Sudeep K, Malathi M. Concordance between free T4 and T4 in thyroid function tests. Int J Clin Biomed Res 2016;2:9-13.  Back to cited text no. 7
    
8.
Hadlow NC, Rothacker KM, Wardrop R, Brown SJ, Lim EM, Walsh JP. The relationship between TSH and free T4 in a large population is complex and nonlinear and differs by age and sex. J Clin Endocrinol Metab 2013;98:2936-43.  Back to cited text no. 8
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9.
Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thyroxine and TSH in the regulation of thyroid function. Eur J Endocrinol 2010;162:1123-9.  Back to cited text no. 9
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10.
Clark PM, Holder RL, Haque SM, Hobbs FD, Roberts LM, Franklyn JA. The relationship between serum TSH and free T4 in older people. J Clin Pathol 2012;65:463-5.  Back to cited text no. 10
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Boucai L, Surks MI. Reference limits of serum TSH and free T4 are significantly influenced by race and age in an urban outpatient medical practice. Clin Endocrinol (Oxf) 2009;70:788-93.  Back to cited text no. 11
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12.
Kahapola-Arachchige KM, Hadlow N, Wardrop R, Lim EM, Walsh JP. Age-specific TSH reference ranges have minimal impact on the diagnosis of thyroid dysfunction. Clin Endocrinol (Oxf) 2012;77:773-9.  Back to cited text no. 12
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13.
Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 2009;94:1251-4.  Back to cited text no. 13
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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