The Relationship between Thyroid Nodules Detected through Ultrasonography and Thyroid Function Test Results in Healthy Individuals

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INTRODUCTION

In Korea, there has been an improvement in thyroid nodule detection through ultrasonography (US) owing to advancements in imaging technologies and growth in the field of health screening.^1,2) Multiple guidelines for thyroid nodules recommend that serum thyrotropin (TSH) levels be measured during the initial evaluation of a patient with clinically

or incidentally discovered thyroid nodules (strong recommendation, moderate-quality evidence).^3-5) However, despite the high prevalence of thyroid nodules detected on US exams,^6-9) little is known about the relationship between the presence of thyroid nodules on US and thyroid function test (TFT) results; hence, the present study aimed to evaluate this relationship.

Received July 25, 2017 Revised August 18, 2017 Accepted August 18, 2017

Corresponding author Soo Hyoung Lee Tel: +82-2-2276-8621, Fax: +82-2-2276-8504 E-mail: [email protected]

ORCID: http://orcid.org/0000-0002-0064-0388

This is an open-access article distributed under the terms of the Creative Commons At- tribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Communication

https://doi.org/10.21215/kjfp.2019.9.1.122 eISSN 2233-9116

Korean J Fam Pract. 2019;9(1):122-124

Korean Journal of Family Practice

KJFP

건강한 사람들에게서 초음파로 발견한 갑상선 결절과 갑상선 기능 검사 사이의 관계

정혜진¹, 문용식¹, 김무영¹, 이수형^1,*, 박기현¹, 김현준¹, 황인영¹, 손윤정¹, 김태호²

1서울의료원 가정의학과, ²서울의료원 내분비대사내과

The Relationship between Thyroid Nodules Detected through Ultrasonography and Thyroid Function Test Results in Healthy Individuals

Hye Jin Jeong¹, Yong Sik Moon¹, Moo Young Kim¹, Soo Hyoung Lee^1,*, Ki Hyun Park¹, Hyun Joon Kim¹, In Young Hwang¹, Youn Jung Son¹, Tae Ho Kim²

Departments of ¹Family Medicine, ²Endocrinology, Seoul Medical Center, Seoul, Korea

Background: The detection of thyroid nodules through ultrasonography (US) has improved with the development of imaging technologies and thyroid cancer screening in Korea. We evaluated the relationship between the presence of thyroid nodules on US and thyroid function test (TFT) results in healthy individuals.

Methods: We performed a retrospective review of data from 449 adults (313 men and 136 women) who underwent tests to evaluate serum thyrotropin (TSH) and free thyroxine levels, thyroid US, and if needed, fine needle aspiration cytology (FNAC).

Results: Of the 449 subjects, 144 subjects (32.1%) had thyroid nodules. Among the 144 with thyroid nodules, 24 (16.7%) were advised to undergo FNAC, and all of them showed normal serum TSH levels. Logistic regression analysis showed that the presence of thyroid nodules was not related to abnormalities noted on TFTs after adjusting for age, sex, smoking status, and presence of risky drinking behavior and hypertension (P=0.647).

Conclusion: The presence of thyroid nodules on US in healthy adults was not associated with abnormal TFT results. Serum TSH check-ups during the evaluation of thyroid nodules discovered through US in asymptomatic individuals living in areas with a low prevalence of autonomous functioning thyroid nodules might not be necessary from the perspective of cost-effectiveness and subject convenience.

Keywords: Thyroid Nodules; Ultrasonography; Thyroid Function Tests; Thyrotropin

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METHODS

1. Study subjects

We retrospectively reviewed the general health check-up database of a health promotion center in Seoul Medical Center. Study subjects were 451 healthy Korean adults who underwent cancer screening between January 1, 2014 and June 30, 2014. All subjects underwent thyroid US and tests to examine TSH and free thyroxine (free T4) levels. Two patients who had undergone total thyroidectomy were excluded. Data on hypertension, diabetes, smoking status, and alcohol-drinking behavior were collected through questionnaires. This study was approved by the Insti- tutional Review Board of Seoul Medical Center (2017-02-005).

2. Thyroid ultrasonography and thyroid function tests Thyroid US was performed using a Logos EUB7500 device (Hitachi, Tokyo, Japan) with linear-array probe (13 MHz). Thyroid nodules were classified into three categories: <5 mm, 5–10 mm, and >10 mm, according to the maximum diameter of the largest nodule. Ultrasound-guided fine needle aspiration cytology (FNAC) was performed when suspicious US findings were observed. Serum TSH and free T4 levels were measured using chemiluminescence immunoassays; the normal range of TSH was 0.35–4.94 uIU/mL and that of free T4 was 0.70–1.50 ng/dL. If either the TSH or free T4 level was abnormal, subjects were classified into the abnormal TFT group.

3. Statistical analysis

General subject characteristics were compared using Pearson’s chi- squared test or Fisher’s exact test for categorical variables, and using the independent samples t-test or Mann-Whitney U-test for continuous variables. To examine whether there was an independent relationship between thyroid nodules and function, multiple logistic regression analysis was performed. Statistical analyses were performed using PASW Statis- tics 18.0 software (IBM Co., Armonk, NY, USA).

RESULTS

1. General characteristics based on the presence of thyroid nodules

Of the 449 subjects, 144 patients (32.1%) had thyroid nodules. The mean age of the group with thyroid nodules was significantly higher than that of the group without thyroid nodules (51.55±8.68 years vs.

47.54±9.89 years, P<0.001). The other baseline features, such as sex, smoking status, alcohol-drinking behavior, presence of hypertension or diabetes, and TSH and free T4 levels, were not associated with the presence of thyroid nodules (Table 1).

2. Abnormal TFT results based on the presence of thyroid nodules, nodular size, and FNAC recommendation

The proportion of individuals with abnormal TFT results did not dif- fer according to the presence of thyroid nodules and nodular size (P=0.588, P=0.932, respectively) (Table 2). Logistic regression analysis Table 1. Characteristics of study subjects

Characteristic Subjects without TNs (n=305)

Subjects with TNs (n=144) P-value

Age (y) 47.54 (9.89) 51.55 (8.68) <0.001

Female 89 (29.2) 47 (32.6) 0.457

Smokers 65 (21.3) 35 (24.3) 0.477

High-risk drinkers 181 (59.3) 76 (52.8) 0.189

Hypertension 45 (14.8) 23 (16.0) 0.737

Diabetes 16 (5.2) 8 (5.6) 0.892

Abnormal TFT results^* 23 (7.5) 13 (9) 0.588

TSH level (uIU/mL)^† 1.94 (1.34) 1.76 (1.35) 0.079 Free T4 level (ng/dL)^† 1.04 (0.12) 1.06 (0.17) 0.140 TNs, thyroid nodules; TFT, thyroid function test; TSH, thyrotropin; Free T4, free thyroxine.

Values are presented as mean±standard deviation or number (%).

P-values were calculated using an independent samples t-test (continuous variables) or Pearson's chi-squared test or Fisher's exact test (categorical variables).

*If either TSH or free T4 levels were abnormal, patients were classified into the abnormal TFT group. ^†Both TSH and free T4 levels showed deviations from a normal distribution; therefore, the Mann-Whitney U-test was performed.

Table 2. Relationship between the presence of thyroid nodules and TFT results

Variable Normal TFT Abnormal TFT^* P-value

TNs 413 36

Presence 131 (90.9) 13 (10.1) 0.588

Absence 282 (92.4) 23 (7.6)

TNs size (mm) 131 13

<5 44 (89.8) 5 (10.2) 0.932

5–10 59 (90.8) 6 (9.2)

>10 28 (93.3) 2 (6.7)

TFT, thyroid function test; TNs, thyroid nodules.

Values are presented as number only or number (%).

P-values were calculated using Pearson's chi-squared test or Fisher's exact test.

*If either thyrotropin (TSH) or free thyroxine (T4) levels were abnormal, patients were classified into the abnormal TFT group. The normal reference range of TSH is 0.35–4.94 uIU/mL and that of free T4 is 0.70–1.50 ng/dL.

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showed that the presence of thyroid nodules was not related to abnormal TFT results after adjusting for age, sex, smoking status, risky drinking behavior, and presence of hypertension (P=0.647). Among 144 individuals with thyroid nodules, 24 were advised to undergo FNAC; 3 showed cytological malignancy but all of them showed normal TFT findings.

DISCUSSION

Our study showed that the presence of thyroid nodules on US did not affect thyroid function results in healthy individuals. Although serum TSH is well-known to be a growth factor for thyroid nodules,¹⁰⁾ its levels did not show any relationship with the presence of thyroid nodules in asymptomatic individuals.

A previous study demonstrated that autonomous functioning thyroid nodules (AFTN) comprise approximately 12% of all thyroid nodules.¹¹⁾ However, in our study, 6 patients (4.2%, 6/144) showed low TSH levels and only 1 (0.7%, 1/144) had overt hyperthyroidism. As AFTN occur more frequently in iodine-deficient areas,^12-14) this low prevalence could be explained by the fact that our study subjects might have been healthy and had normal iodine levels.

The correlation between thyroid nodule size and TSH levels was not significant (P=0.747). A previous study¹⁵⁾ suggested that TSH levels were not effective in assessing the presence of AFTN when the nodule size was small, because thyrotoxicosis was rare with nodules sized less than 2.5 cm. Most thyroid nodules in our study were small, sized less than 1.5 cm.

Our study had several limitations. First, our results cannot be applied to the general Korean population due to some selection bias and the small number of study subjects. Second, patient history and physical ex- amination results could not be obtained owing to the limitations of the health check-up system.

In conclusion, our study showed that the presence of thyroid nodules discovered through US in healthy individuals was not associated with TFT findings. TSH check-ups during the evaluation of thyroid nodules discovered through US in asymptomatic individuals living in areas with a low prevalence of AFTN might not be necessary from the perspective of cost-effectiveness and patient convenience.

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