1 Lithuanian University of Health Sciences
Faculty of Medicine Department of Endocrinology
Title of Master Thesis:
The Association of Thyroid Nodules and Goiter with
Demographic and Clinical Parameters Among Kaunas City
Inhabitants
A Thesis Submitted in Partial Fulfilment of the Requirements for the Degree Master of Medicine
Lithuanian University of Health Sciences
Author: Gabija Ruplyte Supervisor: Prof. Birutė Žilaitienė
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TABLE OF CONTENTS
1. SUMMARY ... 3
2. ACKNOWLEDGMENTS ... 4
3. CONFLICTS OF INTEREST ... 5
4. PERMISSION ISSUED BY THE ETHICS COMMITTEE ... 6
5. ABBRIEVIATION LIST ... 7
6. INTRODUCTION ... 8
7. AIM AND OBJECTIVES ... 9
8. LITERATURE REVIEW ... 10
8.1 Iodine Status ... 12
8.2 Relation to gender ... 13
8.3 Thyroid and metabolic syndrome ... 13
8.4 Lifestyle habits and thyroid ... 14
9. RESEARCH METHODOLOGY AND METHODS ... 16
10. RESULTS ... 19
10.1 Gender and thyroid ... 20
10.1 Nodular changes ... 21
10.2 Goiter ... 22
10.3 Thyroiditis ... 23
11. DISCUSSION OF THE RESULTS ... 24
12. CONCLUSIONS ... 26
13. REFERENCES ... 27
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1. SUMMARY
Author name: Gabija Ruplyte
Research title: The association of thyroid nodules and goiter with clinical parameters among Kaunas city inhabitants
Aim: To investigate association of thyroid nodules and goiter with demographic and clinical parameters among Kaunas city inhabitants
Objectives:
1. To identify thyroid nodules and goiter prevalence in the study group.
2. To investigate relation of thyroid nodules and goiter to gender, age, thyroid hormones levels and autoimmunity.
3. To identify factors independently associated with an increased risk of goiter and thyroid nodules.
Methodology: During biomedical study, randomly selected 25-64 years old, 246 Kaunas city inhabitants underwent evaluation of the thyroid gland. The data was statistically analyzed and presented in order to investigate factors related to goiter and thyroid nodules and their frequency in the study group.
Results: Nodular changes were found in 61 participants of the study (24.8%). 28 of males (20.3%) and 33 of females (30.6%). Goiter was found in 60 subjects (24.3%) and was more common in females (31.5% versus 18.1% in males). Goiter was associated with age (p < 0.001) and thyroid nodularity (p < 0.001). Age was found to have a significant correlation with thyroid nodality (p < 0.001), goiter (p < 0.001), TSH hormone blood levels (p = 0.006), FT4 (p = 0.014) and total thyroid volume (p = 0.026). Thyroid nodules were associated with age (p < 0.001) and goiter (p < 0.001). Men had higher mean total thyroid volume which was significantly higher than in the female subject group (p = 0.008). Thyroid hormone TSH was found higher in the female population when comparing to male (p = 0.006), Anti-TPO was also seen higher in women (p = 0.022), concentration of FT4 was significantly higher in men (p < 0.001). Thyroiditis was present in 24 study subjects (9.7%), it was found to have a moderate correlation with TSH hormone levels (p < 0.001) and gender (p = 0.005).
Conclusion:
1. Goiter and nodular changes were found in 24.3% and 24.8% respectively of the study participants. Prevalence of goiter is seen higher among the female participants when compared to males (p = 0.008), moreover thyroid nodules are seen to have a tendency to appear more in women (p = 0.088).
2. Age moderately correlates with thyroid nodules (p < 0.001) and has low negative correlation with goiter (p < 0.001). Thyroid hormone levels and autoimmunity did not show any significant correlation with thyroid nodules nor goiter.
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2. ACKNOWLEDGMENTS
I express my gratitude to my family who supported me through every step of the way.
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3. CONFLICTS OF INTEREST
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4. PERMISSION ISSUED BY THE ETHICS COMMITTEE
Approved by: LSMU bioethical centerBiomedical research name: The association of thyroid nodules and goiter with clinical parameters among Kaunas city inhabitants
Number: BEC-MF-106
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5. ABBRIEVIATION LIST
Anti-TPO- Anti- thyroid peroxidase antibodies BMI- Body mass index
CT- Computer tomography FNA- Fine- needle aspiration HDL- High- density lipoprotein
HOMA-IR- Homeostatic model assessment of insulin resistance IR- Insulin resistance
MetS- Metabolic syndrome
TSH- Thyroid stimulating hormone T4- Thyroxine
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6. INTRODUCTION
The prevalence of thyroid nodules is high in the clinical practice, making it a common finding. It is detected by palpation to 5-7% of people in the general population. However, large group of individuals might not be aware of nodular changes in the thyroid as its presentation is often asymptomatic and the size of the nodule could be too small for it to be palpated. Therefore, nodules are commonly diagnosed accidently during investigations due to other concerns or conditions. High availability of ultrasound allows diagnosis of non-palpable nodules increasing the incidence rate up to 67% [1].
The development of thyroid nodule has been associated with the female gender, older age and iodine deficient state [2]. These risk factors alone increase the probability; however, the exact pathogenicity is multifactorial and a complex interplay of genetics and environmental factors. Additionally, increased thyroid volume has been positively associated with metabolic syndrome, body mass index (BMI), thyroid stimulating hormone (TSH) levels and smoking [3]. Rise of insulin resistance in general population marks an increase in incidence of thyroid nodules and goiter worldwide.
The relation of iodine and thyroid gland is widely researched as it shows a clear correlation. Insufficient level of iodine is still a common and important matter as approximately 30% of the population around the globe reside in iodine deficient areas [4]. The levels of iodine are crucial for the normal functions of thyroid and lack of iodine is shown to be a significant factor in causing nodular thyroid disease [5]. However, not just the lack but also iodine excess has been shown to have an effect on the gland [6].
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7. AIM AND OBJECTIVES
Aim: To investigate association of thyroid nodules and goiter with demographic and clinical parameters among Kaunas city inhabitants
Objectives:
1. To identify thyroid nodules and goiter prevalence in the study group.
2. To investigate relation of thyroid nodules and goiter to gender, age, thyroid hormones levels and autoimmunity
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8. LITERATURE REVIEW
Thyroid nodules among other thyroid diseases are one of the most common findings. Epidemiological studies show the incidence of palpable thyroid nodules among females is around 5% and among males- 1%, in regards of inhabitants in the areas where iodine levels are sufficient. Studies show an incline of nodule prevalence with an increasing age and for those above the age of 60 years the rate of acquiring a nodule increases up to 50% [7]. Research shows that annual risk in regards of aging for multimodality increases by 1,6%, therefore it could be concluded that aging is one of the main non-modifiable risk factors for thyroid nodules [8].
Most patients with palpable and/or nonpalpable nodule do not experience any symptoms therefore finding can come unforeseen. Due to the growth of the gland and subsequently goiter, perceptible changes in the size of the neck can become noticeable and raise concerns [2]. Generally, thyroid nodules become palpable when they reach the size of 1 cm. However, only a small portion of nodules are diagnosed by self-palpation or during a physical examination by a physician. The rate of diagnosing nodules is much higher when it is done instrumentally by the ultrasound (US) or computer tomography (CT) if compared to palpation [1]. Furthermore, some nodules are diagnosed accidentally and are referred to as incidentalomas, it is a common finding in the thyroid gland [9].
During ultrasound diagnostics thyroid nodules are visible due their radiological distinction to the surrounding parenchyma [10]. The smaller nodules that cannot be palpable can be diagnosed instrumentally. The homogeneity, echogenicity, size of each nodule, their borders and any feasible microcalcifications are noted during an examination. The dimensions and volume of the thyroid gland are also measured. Furthermore, information obtained from an ultrasound investigation is complemented with blood samples for thyroid function panel hormones and patient’s anamnesis for further development of the assessment.
11 noted as features of potential malignancy [12]. Gharib et al. [13] recommend following the diagnosis of a nodule to proceed with a serum TSH test, ultrasound examination and fine- needle aspiration (FNA) for the selected patients with risk factors, euthyroid status and larger nodules of above 1-1,5cm in order to exclude cancerous nodules from benign ones. Features on the ultrasound that should rise suspicion of malignancy include irregularity of nodular borders, intranodal hypervascularity and macrocalcifications [12]. Additionally, it has been suggested that normal or high TSH is usually associated with possibly malignant nodule while low TSH generally suggest a benign thyroid nodule [11].
Thyroid hormones and thyroid nodules have an immense relationship. Thyroid stimulating hormone (TSH) in particularly. It is a hormone produced by the anterior pituitary gland it drives thyroid gland to release thyroid hormones. Elevated levels of TSH induce proliferation of thyrocytes and cause nodular changes. Any factor causing an increase of the levels of TSH will cause nodular formation e.g., increased levels of iodine or pregnancy. Hence, even a moderate increase of TSH over some time induce changes in thyroid volume causing goiter [14]. Study done in Lithuania has shown that increased levels of TSH is associated risk factors for thyroid nodules [3]. Moreover, research shows that higher levels of hormone were seen more commonly in the patients with malignant thyroid nodules while low TSH was more likely to indicate a benign nodule [15]. Therefore, measuring TSH upon diagnosis of thyroid nodule might be helpful with assessing and even treatment decisions [16].
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8.1 Iodine Status
Iodine status is a crucial factor concerning thyroid diseases especially nodules and nodular goiter. Mainly concentrated in developing countries, it marks a strong relation to reduced availability and intake of ionized salt and peculiarities of low iodine diet [17]. These areas are especially vulnerable when it comes to thyroid diseases, however iodine deficiency is noticed in developed countries as well. Borderline iodine deficiency is especially recognized in pregnant and lactating women who have increased demand of iodine [18]. This group of people is required to increase their daily iodine intake until the sufficient levels to ensure normal function of the thyroid gland. Reduced concentration of iodine leads to reduced production of thyroid hormones as this micronutrient is crucial for synthesis of triiodothyronine (T3) and thyroxine (T4), however excess of iodine could be also inducing thyroid dysfunction in selected number of individuals [6]. Furthermore, thyroid nodule pathophysiology in case of iodine deficiency is due to increased TSH stimulation on thyroid. This eventually leads to hyperplasia and hypertrophy of the organ causing nodular changes [19].
Global iodination i.e., introducing ionized salt and foods containing elevated levels of iodine has been implemented in order to sustain sufficient levels of iodine and to reduce related diseases. It has shown great results in reducing endemic goiter incidence by nearly half in mainland of China [20]. However, it has led to excess of iodine consumption in some areas of the world. Results of a study show that both excess and lack of iodine have a direct effect on TSH concentration [21]. This leads to an understanding that not even low but also excessive amounts of iodine have a negative effect on the thyroid and its functions.
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8.2 Relation to gender
In the study previously done in Lithuania, 317 participants were evaluated; their TSH, T4 and antithyroid peroxidase antibody (Anti-TPO) levels were measured and noted along with anthropometric and metabolic parameters as well as their smoking habits. Thyroid nodules were seen in 31,2% of the subjects. The incidence was much higher in females than males 40,6% and 19,7% respectively. Similarly, goiter was also more prevalent in females 15,4%, versus 8,5% in males [3]. This trend among women has been researched and has shown a strong relation to estrogen levels. Estrogen depended non genomic and genomic pathways effecting the mitotic function of the thyroid cells. Increased endogenous levels of estrogen through membrane bound estrogen receptors subsequently upregulates the growth receptors and increase cell proliferation [23].
Furthermore, progesterone has also been proven to be affecting the rate of proliferation of the thyroid follicular cells. Similarly, to the action of estrogen it acts through genomic pathways. However, increased gene expression does not necessarily cause increase in proliferation and mitosis of the cells in all cases [24]. Study shows that pregnancies and multiparity also play a role in development of thyroid nodules with statistically significant difference when compared to women without children. However, goiter was not found to have relation to woman’s parity. Furthermore, the association was proposed to be linked to increased iodine requirements during pregnancy leading to formation of thyroid nodules in the areas of lower iodine status [25]. Additionally, another research supported that gravidity has impact on formation of new nodules as well as enlargement of preexisting ones while also possibly predisposing for goiter later in life [26]. Therefore, in conclusion research supports the claim that females are much more susceptible to nodular thyroid diseases.
8.3 Thyroid and metabolic syndrome
14 body weight and body mass index (BMI) established that people who are overweight or obese are more likely to have thyroid nodular disease [27]. Furthermore, goiter was shown to have a positive core [3].
Metabolic syndrome is widely seen among the obese population and is often associated with insulin resistance (IR) and increased risk for type 2 diabetes. Kir et al. [28] show that thyroid nodules and goiter were more prevalent among those having MetS [29]. Insulin resistance produces high levels of circulating insulin. It has a mitogenic effect on the thyroid follicular cells causing hyperplasia and growth of thyroid nodules. Besides increased division of the thyrocytes, insulin has an antiapoptotic property meaning that cells’ apoptosis is delayed prolonging its life [5].
Homeostatic model assessment of insulin resistance (HOMA-IR) (calculated according to the formula: fasting glucose mmol/L multiplied by fasting insulin mIU/L and divided by 22.5) is widely used in order to determine insulin resistance and beta- cell function. Tsatsoulis et al. [30] propose that higher HOMA-IR is associated with higher prevalence of thyroid nodules. In addition to this, research shows that size and volume of a nodule is positively correlated with HOMA-IR [5]. In obese population a correlation is seen between HOMA-IR and the level of obesity. Moreover, the positive association between HOMA-IR and TSH revealed that obesity and its effect on the metabolism might have a direct effect on the serum levels of TSH [31]. High levels of TSH further leads to increased proliferation of the thyroid follicular cells causing the formation of the nodules [14].
8.4 Lifestyle habits and thyroid
15 Putting it in perspective that possibly the levels of iodine and other risk factors such female gender are more significant in the pathophysiology of thyroid nodules. This could be demonstrated that in case of female gender smoking was significantly correlated to thyroid nodules prevalence while male smokers did not have an increased incidence rate when compared to non-smokers [33]. Moreover, other research shows the incidence of increased risk of nodular disease for smokers is mainly observed in areas of low iodine status indicating the relation of both factors [2]. Hence, more research is required in order to confirm smoking as an independent risk factor for goiter and nodules while excluding other established factors.
Lifestyle involves several, already described possible risk factors for thyroid nodules and goiter. Smoking, diet and exercise predisposing to metabolic syndrome has already confirmed relation to the condition. However other aspects of lifestyle choices might have an effect on formation of nodular changes in the thyroid. Alcohol consumption was found to have a negative correlation to volume of thyroid, as individuals who were drinking more were less likely to have goiter and solitary nodules as research shows. Specifically, consumption of wine and beer was shown to lead to lower incidence of nodular disease [34]. However, these results are very controversial and should not encourage alcohol consumption as alcohol carries many other health risks. It is crucial to emphasize that nodular abnormalities are the interaction between genetics and environmental factors that are individual in each case and could carry higher exposure risks for selected individuals with higher susceptibility for certain conditions.
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9. RESEARCH METHODOLOGY AND METHODS
Biomedical study “Lėtinės ligos ir jų rizikos veiksniai suaugusių žmonių populiacijoje“ (Chronic diseases and their risk factors among adult population) approved by the Lithuanian Bioethics Committee. It was carried out in LSMU university hospital, Kaunas clinics starting 2018 and was estimated to last until 2021. The aim of the study was to investigate the main chronic diseases, their risk factors, prevalence and their interconnection.
The study involves Kaunas city residents in the age group 25-64 years. Individuals participating in the study were selected randomly through Lithuanian citizen registry. Those who were chosen, received an invitation to arrive for examinations. All participants were ensured anonymity and data protection, agreeing to participate by signing a consensus form. The size of the group was adapted significantly amid the ongoing pandemics and number of subjects was greatly reduced. Therefore, total of 246 subjects (138 males and 108 females) participated in the study.
Selected subjects went through numerous of examinations in order to evaluate their well-being and general health status. For the purpose of this master thesis the relevant data was selected concerning the aim and the objectives accordingly. The extend of this master thesis was adjusted dramatically due to the circumstances and lots of the necessary data to develop the thesis further was unfortunately unavailable.
Regarded examination included short description of the procedure, filling in a standardized questioner and thyroid palpation following ultrasound examination carried by a doctor. Imaging diagnostic ultrasound machine Toshiba, model SSA510A, CE 0197 was used throughout the investigation. Echogenicity, homogeneity and dimensions of each lobe of the thyroid were documented. Any nodular changes were noted for left and right lobe respectively. Each nodule was measured and characterized by shape, border regularity, microcalcifications, structure and assigned according to EU-TIRADS grade.
17 assigned for nodules that carry high risk of malignancy estimated to be 26-87%. High risk factors include irregular shape and borders, microcalcifications and significantly hypoechogenic nodule. Upon diagnosis of EU- TIRADS 5 class nodule exceeding 10 mm, FNA has to be done, except the cases when patient is non operable, or the chance of survival is low due to comorbidities. According to the presence of alarming malignancy features nodules were divided into high and low risk groups to further assess the risk and necessity of FNA for microscopical evaluation (Annex 2.).
The volume of each thyroid gland was calculated using the formula: width (cm) × length (cm) × depth (cm) × 0.479 for each lobe, the volume of the entire thyroid gland was achieved by summing both lobes. Goiter was determined by total thyroid volume exceeding the normal ranges- 18mL and 25mL, for females and males respectively.
Samples for biochemical analysis included 5 ml venous blood sample acquired by venipuncture of vein of the forearm. Laboratorial evaluation for the serum levels of FT4, TSH and Anti-TPO antibody was completed and will be applied and analyzed statistically for the purposes of this work. The reference values: Anti-TPO 0-60U/ml, FT4 11.5-23.0 pmol/l and TSH 0.2-3.2IU/l.
Data was organized and assessed by using statistical analysis. Normality of the variables was determined by using Kolmogorov-Smirnov test. According to the distribution of variable being normal or non-normal, variables were demonstrated in terms of ± standard deviation (SD) and median and interquartile range (IQR) respectively. In order to compare two continuous variables, the tests were used according to the normality (distribution) of a variable. For normal distributed variables Student’s t test was applied and in contrast whenever the variables did not meet the normality criteria they were assessed according to the Mann-Whitney test. These tests were applied to evaluate categorical and continuous variables. Correlation between variables was evaluated using Pearson and Spearman correlation tests depending on the data being parametric or not.
When calculating the correlation between the nominal such as in this case the presence of thyroid nodule and its absence which can be also referred to as independent variable and hormone levels of TSH, FT4 and Anti-TPO i.e., the depended variables, the statistical measurements involve a nominal and interval scaled variable due to that Eta statistic (SPSS) was used to evaluate the strength of the correlation and so-called association as a part of ANOVA, chi-squared test group. Chi-square test was used for two nominal variables assessment. The association between goiter, thyroid nodules and thyroid hormone levels were done by using binary logistic regression analysis.
18 were missing for different subjects, missing values were excluded pairwise in order to achieve correct correlation values, however this let to even smaller sample numbers for each of the variables.
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10. RESULTS
The age of the study participants is between 65 and 25 years of age. Mean age among the participants of the study is 45,4 years old. Positive correlation between age and thyroid volume Pearson correlation 0.147, significant as ρ = 0.026 (p < 0.05). In the scatter Diagram 1. the correlation between age and total thyroid volume of the participants is showed where some of the higher total volumes are seen as the age of the subjects increases as well as the highest volumes were found in older individuals that participated in the study. Furthermore, the findings look more dispersed as the age increases. Age was also found to have a significant moderate correlation with thyroid nodality as Pearson correlation 0.309 (p < 0.001), low negative correlation with goiter ρ = -0.298 (p < 0.001) and low correlation with TSH hormone blood levels ρ = -0.215 (p = 0.006) and FT4 ρ = -0.194 (p = 0.014).
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10.1 Gender and thyroid
In the study total of 246 subjects were participating of whom there were 138 males and 108 females. Mean thyroid volume in the research group was found to be 11.6 ± 7.4mL. Men had higher mean total thyroid volume which was significantly higher than in the female subject group (p = 0.008). Prevalence of goiter was calculated to be higher in women than men (p = 0.015). Tendency of thyroid nodules presence among women was observed (p = 0.088). Thyroid hormone TSH was found higher in the female population when comparing to male (p = 0.006). Furthermore, Anti-TPO was also seen higher in women (p = 0.022). Moreover, the concentration of FT4 was significantly higher in men (p < 0.001). Findings are summarized in the Table 1.
Table 1. Characteristics of study population
Characteristic Men (n = 138) Women (n = 108) p value
Thyroid volume (mL)∗ 12.7 ±6.7 10.2 ± 8.1 0.008 Prevalence of goiter, n (%) 25 (18.1) 34 (31.5) 0.015 Prevalence of thyroid nodule, n (%) 28 (20.3) 33 (30.6) 0.088 Anti-TPO (U/ml)** 17.6 (2.7) 326.5 (12.8) 0.022 TSH (IU/L)** 1.8 (1.1) 3.2 (1.7) 0.006 FT4 (pmol/L)* 18.3 ± 2.2 16.6 ± 2.5 <.001
21 The echogenicity of the thyroid gland was evaluated found in 226 subjects from whom it made up 134 males and 92 females. 97.1% of the males had normal thyroid echogenicity while percent for the females was slightly lower- 85.2%. Moreover, homogeneity was found to be less frequent among the females than males in the study group (97.1% of the males versus 85.2% of the females).
10.1 Nodular changes
Nodular changes were found in 61 participants of the study (24.8%). 28 of males (20.3%) and 33 of females (30.6%) have had been detected to have at least one nodule. 45 participants had nodule on the right side, 35 had on the left side.
Number of nodules varied from one to maximum of 7 nodules found in an individual. Findings show that, 42 individuals had a single nodule (66,7% of all who had nodules, 17,0% of all subjects), 11 individuals had 2 nodules (17.5% of all who had nodules, 17.5% of all subjects), 6 individuals had 3 nodules (9.5% of all who had nodules, 2.4% of all subjects), 1 individual had 5 nodules (1.6% of all who had nodules, 0.4%of all), single individual had 6 nodules (1.6% of all who had nodules, 0.4% of all) and 1 individual had 7 nodules (3.2% of all who had nodules, 0.8% of all).
Nodules were divided into low and high risk according to their appearance on the ultrasound. The vertical orientation, border irregularity and any visible microcalcifications were noted to describe the features suggestive of potential risk of the nodule. Two subjects had high risk nodules of whom one female and one male of whom only 1 was larger than 10mm. Low risk nodules were observed more frequently and was found in 14 individuals (5.7% of all subjects).
EU- TIRADS grading system was implemented to indicate potential risk regarding the nodular changes.
• EU- TIRADS 2- was observed in 16 females (14.8% of all females) and 17 males (12.3% of all males).
• EU- TIRADS 3- 16 females (14.8% of all female subjects) and 10 males (7.2% of all male subjects).
• EU- TIRADS 4- 7 females (6.5% of all female subjects) and 6 males (4.3 % of all of all male subjects).
22 Among subjects who had been assigned EU- TIRADS 5, one female had a nodule larger than 10 mm suggestive of FNA. However, FNA revealed no changes indicative of malignancy.
Furthermore, nodule of size larger than 20 mm was noted among 3 females and 2 males who subsequently required fine needle aspiration procedure.
During the statistical analysis, correlation methods were implemented, they revealed that thyroid nodules were associated with age Pearson correlation 0.309 (p < 0.001) and strong negative significant correlation with goiter ρ = -0.881 (p < 0.001).
Eta statics value is functional when it comes to association between presence of a nodule and TSH and FT4, Eta Coefficient test statistic η = 0.057 and η = 0.016 respectively, point out that there is very weak association between the variables if not none. However, Eta Coefficient test statistic for Anti-TPO was found to be η = 0.127 which shows slightly higher though remaining weak correlation. Eta square 0.016, concluding that independent variable in this case the nodality of thyroid affects depended variable- Anti-TPO hormone levels only by 1.6%.
The Table 2. shows subjects that were divided into two separate groups according to thyroid nodality. Thyroid volume showed negative correlation with TSH hormone in non- nodular thyroid group. In subjects without nodules thyroid volume also correlated with FT4 hormone. In the nodular thyroid group, the findings were unsignificant.
Table 2. Relationship between thyroid volume and different variables in subjects with and without thyroid nodules
Characteristic Thyroid Volume
Nodular Thyroid Non-nodular Thyroid
ρ p value ρ p value
TSH (mU/L) -0.270 0.092 -0.214 0.017
FT4 (pmol/L) 0.020 0.909 0.222 0.012
Anti-TPO (IU/L) -0.107 0.552 0.130 0.153
10.2 Goiter
23 0.001), strong negative correlation with nodularity ρ = -0.881 (p < 0.001) and naturally the total volume of the thyroid ρ = -0.277 (p < 0.001).
The multivariate logistic regression analysis did not show any significant association between the hormones, goiter and thyroid nodules (Table 3.)
Table 3. Multivariate analysis of associations of goiter and thyroid nodules with analyzed factors
Variable Goiter Thyroid nodule
OR (95% CI) p value OR (95% CI) p value
TSH (mU/L) 1.00 (0.87–1.16) 0.967 0.99 (0.86–1.16) 0.948
FT4 (pmol/L) 1.01 (0.86–1.18) 0.921 1.04 (0.88–1.22) 0.664
Anti-TPO (IU/L) 1.00 (1.00–1.01) 0.301 1.00 (1.00–1.01) 0.246
10.3 Thyroiditis
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11. DISCUSSION OF THE RESULTS
The study has shown that the age of the individuals studied in the study and total thyroid volume were significantly correlated (p = 0.026). This finding, however, is fairly limited due to the reason that advancing age has a tendency of weight gain, as metabolism slows down significantly. Consequently, body weight and body fat percentage play a crucial role in the total volume and size [38]. However, unfortunately BMI and other body weight mass concerning calculations cannot be assessed and evaluated due to the lack of such data regarding the weight of the study participants. Furthermore, age was found to have a significant correlation with thyroid nodality (p < 0.001), goiter (p < 0.001), TSH hormone blood levels (p = 0.006) and FT4 (p = 0.014). Importantly, FSH hormone level change correlation with age was also supported by research done previously [39]. However, the effects of thyroid gland function and hormone production in regards of aging population might have an individual effect which should be researched in future studies.
Additionally, the findings in the study include that males differentiated from females by having higher mean total thyroid volume, significantly, as p = 0.008. A study supports this result, however, claims that the relationship was merely seen due to the weight differences between the genders [40]. This further concludes that additional interpretations of the results are limited due to the reason that the weight was not measured during the study and cannot be accessed.
Thyroid volume correlated with TSH hormone in the study. This is supported by literature as TSH is seen as the main mitotic factor in the thyroid gland. Further, increased levels of TSH potentially leads to thyroid nodality. However this thesis cannot conclude such results as they were not proven as significant. Nevertheless, many factors such as iodine status, the presence of the metabolic syndrome and variable degree resistance to insulin should be explored to research the relevance and correlation with thyroid nodality as they seem to have extensive effect on the thyroid as research shows [14]. During research, results determined goiter to have a significant correlation with levels of TSH as this is consistent with the finding of TSH correlation with total volume of the thyroid, naturally, as goiter is chiefly characterized as increased total thyroid volume.
25 The levels of hormones among the genders showed higher levels of TSH among the females when compared to males. This possibly led to higher prevalence of thyroid nodules and goiter in this certain group of subjects. Other related findings could be explored further when taking into an account the levels of hormones such as estrogen in the female population and having data about the parity to be able to make more clear and developed conclusions regarding higher levels of TSH present in women and its relation to thyroid which has been mentioned in other study [41]. However, the concentration of FT4 was significantly higher in men this finding alone does not entail any conclusions as its cause remains unclear and cannot be evaluated to a greater extend due to the lack of additional data in the study.
Thyroiditis was found to have a strong correlation with TSH hormone levels (p < 0.001) and gender (p = 0.005) as women were more likely to have higher levels of Anti-TPO and to have met theoretical thyroiditis requirements of Anti-TPO < 60 IU/L.
Major limitation and error include the relatively small number of the study participants. It should be noted, the study was adjusted amid the COVID-19 pandemics. Unfortunately, many of the intended evaluations of the specific hormones and metabolic parameters were not done accordingly, therefore the objectives and focus of the research had to be modified and narrowed. Due to the circumstances the number of the participants in the study was altered significantly. Therefore, it is difficult to implement the results and apply them to the scale of a larger population. However, the study resulted in numerous findings that were discussed and described above.
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12. CONCLUSIONS
1. Goiter and nodular changes were found in 24.3% and 24.8% respectively of the study participants. Prevalence of goiter is seen higher among the female participants when compared to males (p = 0.008), moreover thyroid nodules are seen to have a tendency to appear more in women (p = 0.088).
2. Age moderately correlates with thyroid nodules (p < 0.001) and has low negative correlation with goiter (p < 0.001). Thyroid hormone levels and autoimmunity did not show any significant correlation with thyroid nodules nor goiter.
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31
14. ANNEXES
Annex 1.
EU-TIRADS klasifikacija
pagal 2017 m. “European Thyroid Association Guidelines for Ultrasound
Malignancy Risk Stratification of Thyroid Nodules in Adults: The EU-TIRADS”
Aprašymas
Vaizdas
EU-TIRADS 1
• Šiai kategorijai priskiriama skydliaukės UG, kurio metu nebuvo rasta mazgų
EU-TIRADS 2
• Gerybinių pakitimų kategorija • Piktybiškumo rizika 0 % • APPA neindikuotina • Priskiriama:
• Aiškios (“švarios”) anechogeniškos cistos:
• neturi solidinio komponento • dydis nesvarbus
• Cistos, kurios turi pertvarėles dalijančias jas į kelias kameras. Cistos viduje gali būti stebima echogeniška dalis, kuri dažniausiai būna sutirštėjęs fibrinas, arba solidinis komponentas
• “Kempininiai” mazgai:
• Visas mazgo tūris sudarytas iš mažų
cistinių intarpėlių, atskirtų izoechogeniškomis pertvaromis
• Dydis nesvarbus
32
EU-TIRADS 3
• Mažos rizikos kategorija • Piktybiškumo rizika 2-4 %
• APPA atliekama tik esant >20 mm dydžio mazgui
• Jeigu stebima susijungusių mazgų grupė – konglomeratas, APPA turėtų būti
atliekama, jeigu 1 arba daugiau mazgų >20 mm dydžio
Priskiriama:
• Ovalios formos, izoechogeniški arba hiperechogeniški mazgai su lygiais kraštais
• Mišrūs mazgai (kai cistiniai tarpeliai sudaro ne visą mazgo tūrį).
EU-TIRADS 4
• Vidutinės rizikos grupė • Piktybiškumo rizika 6-17 %
• APPA rekomenduojama esant mazgui >15 mm.
• Skirtumas tarp mažos ir vidutinės rizikos grupės – echogeniškumas ir solidinė mazgo dalis.
• Jeigu mazgo solidinė dalis yra heterogeniška ir turi bent kažkiek hipoechogeniško audinio – mazgas priskiriamas vidutinės rizikos grupei. • Jeigu mazgas turi kitų požymių: apjuostas
plonu halo, yra dalis cistinio komponento, “kometos uodegos” artefaktų, stebima periferinė kraujotaka, mazgas minkštas – tai sumažina piktybiškumo riziką.
Priskiriama:
• Ovalios formos, lygiais kraštais, švelniai hipoechogeniški mazgai.
EU-TIRADS 5
• Didelės rizikos grupė
• Piktybiškumo rizika 26-87 %
Priskiriama:
• Mazgai, kurie turi bent 1 didelės piktybiškumo rizikos požymį:
a) netaisyklinga forma b) neaiškios ribos c) mikrokalcinatai d) ženkliai
hipoechogeniškas mazgas • Esant šiems požymiams, jeigu mazgo
dydis >10 mm, turi būti atliekama APPA, išskyrus tuos atvejus, kai pacientas neoperabilus arba yra maža
33 • Piktybiškumo rizika didėja su kiekvienu
įtartinu požymiu
• Jeigu atlikus APPA nustatyti gerybiniai požymiai, po 3 mėn. APPA turi būti pakartota, siekiant išvengti klaidingai neigiamų rezultatų.
• Jeigu mazgas <10 mm, tačiau turi didelės piktybiškumo rizikos požymius, įvertinus ar nėra patologinių l/m ir sutikus
pacientui, rekomenduojamas aktyvus sekimas atliekant UG.
• Stebint mazgo didėjimą, arba nustačius įtartinus pakitimus l/m, turi būti atliekama APPA.
Daugybiniai mazgai
Rekomendacijos:• Įvertinti ir aprašyti didelei rizikai priskiriamus mazgus, neatsižvelgiant į jų dydį. Tačiau APPA atlikti jeigu mazgas >10 mm.
• 2.Įvertinti vidutinės rizikos mazgus ir aprašyti jeigu mazgas >5 mm. Tačiau APPA atlikti jeigu mazgas >15 mm.
• Įvertinti mažos rizikos mazgus ir aprašyti jeigu mazgas >10 mm. Tačiau APPA atlikti jeigu mazgas >20 mm.
34
Annex 2.
Skydliaukės mazgas
Bent 1 piktybiškumo
požymis Piktybiškumo požymių nėra
