Comparison of the sonography index of thyroid gland with serum level of Anti-thyroid peroxidase, Anti-thyroglobulin and thyroid function test in patients with Hashimoto thyroiditis

doi:10.21203/rs.3.rs-835595/v1

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Research Article

Comparison of the sonography index of thyroid gland with serum level of Anti-thyroid peroxidase, Anti-thyroglobulin and thyroid function test in patients with Hashimoto thyroiditis

https://doi.org/10.21203/rs.3.rs-835595/v1

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Background

The purpose of this study was to determine the association of sonographic parameters with the serum levels of anti-thyroid peroxidase (TPO), anti-thyroglobulin (Tg), and thyroid hormones in patients with Hashimoto's thyroiditis.

Methods

149 patients (118 females, 31 males; aged 18–60 years; mean age: 38.60 ± 8.03 years) who were diagnosed with Hashimoto's thyroiditis were enrolled in the study. Blood sample was taken to measure the serum levels of free T3 and T4, thyroid stimulating hormone (TSH), anti-TPO antibody titers, and anti-Tg antibody titers. The thyroid sonography of each patient was classified into one of the five grades by real-time ultrasonography (US) based on echogenicity, thyroid size, and thyroid pattern. We evaluated whether a correlation existed between thyroid characteristics on US and serum levels of thyroid hormones, anti-TPO and anti-Tg.

Results

Nodular structures were detected in 54 (36.2%) patients (38 micronodular and 16 macros nodular). Echogenicity was recorded as isoechoic in 15 (10.07%) and hypoechoic in 119 (79.87%) subjects. Euthyroid ‎subjects had significantly thicker isthmus than overt and subclinical hypothyroid patients (p = 0.018). Mean serum TSH, anti-Tg and anti-TPO titers was significantly higher in patients with micronodules than those with micronodules and subjects without nodules (P < 0.05). Isthmus thickness had a significant negative correlation with FT4 and FT3 (P = 0.046; r = 0.11& P = 0.017; r = 0.15, respectively). Thyroid autoantibodies had positive significant correlations with different parameters of the thyroid volume (P < 0.05).

Conclusions

Thyroid’s US findings in addition to serum levels of anti-Tg and anti-TPO titers would be useful in diagnosis and evaluation of the severity and extent of Hashimoto's thyroiditis, but further evaluations are needed.

Trial registration:

Trial registry identifier IR.SUMS.REC.1395.S161 (2015/11/30).

Endocrinology & Metabolism

Hashimoto’s thyroiditis

anti-thyroid antibody

thyroid ultrasonography

Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease, which is dependent on anti-thyroid antibodies [1]. It is a common disease that affects up to 2% of all women in the community, usually between the ages of 30 and 50. Hashimoto’s thyroiditis is one of the most common causes of hypothyroidism, which might be subclinical in 90% of patients [2]. A definitive diagnosis is established by sampling the thyroid gland, but this method is rarely performed. Hashimoto's thyroiditis diagnosis is based on clinical findings and the results of biochemical and serological tests [3]. During clinical examination, diagnosis is related to the signs and symptoms of hypothyroidism, goiter with a firm feeling during the physical examination, and a Delphian node [2]. High levels of anti-thyroid peroxidase (TPO) anti-body titer or anti-thyroglobulin (Tg) anti-body titer in the serum confirms the diagnosis; Serum level of thyroid stimulating hormone (TSH) and free T4 hormones measurements and imaging studies, such as thyroid ultrasonography (US), are used to diagnose Hashimoto's thyroiditis. High levels of anti-TPO antibody are found in 95% of patients with Hashimoto 's thyroiditis [4]. Furthermore, anti-Tg antibody positivity was present in 70% of patients. However, anti-Tg antibody are found in 5% of the general population. Although there is a strong association of the presence of anti-TPO antibody with Hashimoto's thyroiditis, it is unclear whether the anti-TPO antibody titer or anti-Tg antibody titer are directly causative or merely a marker of ongoing thyroid cell disruption [5]. US examinations is widely safe, non-invasive, available, easy-to-use, and less expensive than other imaging methods. Advanced US imaging in recent years not only has been so amazing for radiologists, but also has fascinated clinicians to use these techniques in their daily clinical practice. Advances in thyroid imaging have considerably improved the diagnosis, treatment, follow-up, and prognosis of high prevalence thyroid diseases. The sonographic presentation of Hashimoto's thyroiditis includes a wide range of findings. Typically, thyroid US reveals a large, heterogeneous, and hypoechoic thyroid gland. A micro-nodular pattern strongly supports the detection of Hashimoto's thyroiditis [6]. Thyroid US is an ideal imaging modality in the evaluation of the thyroid gland, and the relationship between decreased echogenicity, or irregular echo pattern in the US, and thyroid dysfunction is well known. The sonographic finding can play a role in objective identification of active and latent patients with autoimmune disease. However, the relationship between antibody levels and thyroid sonographic findings is not clear [7]. The classification of gray-scale findings in Hashimoto's thyroiditis is originally created by Sostre and Reyes [8]. There are some descriptive grading systems that describe follow-up sonographic scans based on sonographic parameters. However, these classification systems have not yet been widely used in clinical practice. The interplay between thyroid hormone action and the immune system has been established in physiological and pathological settings. Moreover, increasing evidence suggests the role of hormone replacement treatment in modulation of the immune response [9].

The findings in this study may contribute to a broader understanding of agreement of serological and sonographic markers for Hashimoto’s thyroiditis. Most of the available literature on diagnostic studies in the field of Hashimoto’s thyroiditis has been performed on hypothyroid patients receiving thyroid replacement therapy. To do so, further research is needed to compare the correlation of these sonographic findings and related grading classification with the severity of the disease. The aim of this study was to find out whether there is a correlation between sonographic parameters of the thyroid and autoantibody activity in patients with Hashimoto's thyroiditis in patients not receiving thyroid hormone replacement therapy. Therefore, we evaluated whether significant differences existed in the antibody activity, thyroid function test, the sonographic finding that may show the evolution of anti-thyroid antibody and thyroid function tests, and the sonographic score of the Sostre and Reyes grading system.

Study Design

This descriptive cross-sectional study was conducted from January 2018 to May 2019 on patients who were referred to the endocrinology clinics affiliated to Shiraz University of Medical Sciences with a possibility of thyroid dysfunction and were not under medical treatment. 149 subjects (118 females, 31 males aged 18–60 years old with a mean age of 38.60 ± 8.03 years) who had the criteria for the diagnosis of Hashimoto's thyroiditis were selected by simple random sampling. Patients with a positive history of thyroid dysfunction or malignancy and those who consumed drugs that affected thyroid function (e.g. thyroid hormones, thionamides, radioactive iodine, or oral contraceptive pills) and pregnant ones were excluded. All procedures performed in the study were in accordance with the ethical guidelines of the Declaration of Helsinki and the ethics committee of Shiraz University of Medical Sciences has approved the study protocol.

Setting

After explaining the study objectives, the participants were asked to sign a written informed consent. Then, a questionnaire containing questions about demographic, educational and marital status, individual habits, history of thyroid disease, and current medications were filled out by a trained nurse. Weight was measured using a mechanical balance scale (Seka Vogel and Halke, Hamburg, Germany) with a precision of 0.5 kg. Height was measured to a precision of 0.5 cm in the upright position using a portable stadiometer (SECA stadiometer). Waist circumference was measured midway between the lower rib margin and the superior anterior iliac spine by means of a non-stretchable tape. Based on WHO classification criteria [9], clinical examination of the thyroid for the presence of goiter, thyroid consistency, presence or absence of the nodule, and their size was performed on the participants by an endocrinologist.

Laboratory Tests

Blood samples (10 ml) were collected in standard tubes for the measurement of free T3 and T4 (RIA, Immunotech, Czech), TSH (IRMA, Immunotech, Czech), anti-TPO titer and anti-Tg titer (Competitive RIA, Immunotech, Czech) and sent to Nemazi Hospital Endocrine Research Center affiliated to Shiraz University of Medical Sciences. All tests were performed by the same commercial kits. Free T3, free T4, and TSH levels of 2.5–5.8 pmol/L, 11.5–23 pmol/L and 0.17–4.05 mIU/mL were taken as normal values, respectively. Anti-TPO and anti-Tg titer > 60 IU/mL were considered positive. Subclinical hypothyroidism has been described as TSH > 4.05 mIU/mL with normal FT4. Serum TSH level > 4.05 mIU/mL and FT4 < 11.5 pmol/L is described as overt hypothyroidism.

Ultrasonography

According to standard sonographic recommendations, the patients were positioned by lying supine with the neck in a slightly hyper-extended position. Then, scanning was done both in transverse and longitudinal planes by using a (HONDA ELECTRONIC HS-2200, Japan) sonographic machine with a 7.5-MHz transducer. Ultrasound examinations were performed by a sonographer trained in thyroid ultrasound for all patients. Various assessments were recorded [10]. Thyroid volume was calculated using the three-axis method. The lobes of the thyroid were considered to be elliptical, and the volume of each lobe was calculated using Brunn's formula (volume (ml) = length × width × thickness × 0/479) and the total thyroid volume from the total volume of the two lobes disregarding the isthmus. The average normal volume of the thyroid gland in non-goiter subjects in males and females was reported to be 12 to 18 ml and 10 to 15 ml, respectively. The patients with thyroid volumes greater than these values were classified as having thyromegaly. The echogenicity was compared to the adjacent strap muscles and categorized as isoecho and hypoechoic when its echogenicity was equal to or less than the strap muscles. Based on the gray scale, thyroid nodules were divided into two macronodular and micronodular variants. Nodules were called micronodules when their size was ≤ 6 mm [11]. Based on analyses of gray-scale sonographic features, thyroid patterns were categorized according to the following scale (Grading system created by Sostre and Reyes) [8]: (G0): Thyroid gland with normal size and echogenicity, (G1): Large diffuse gland with normal echo (similar to normal tissue ecology), (G2): Multiple hypoechoic foci or patches scattered throughout an otherwise normoechoic gland which is more indicative of focal rather than diffuse involvement, (G3): Enlarged gland with diffuse but mild hypoechogenicity, and (G4): Enlarged gland with diffuse and marked hypo-echogenicity.

Data analysis

Data were analyzed using by t-test, Chi-square, and one-way ANOVA. Non-parametric tests (for data that did not have a normal distribution) such as the Kruskal Wallis and Mann Whitney were also performed using SPSS software (version21, Chicago, IL). P-value < 0.05 were considered significant.

Baseline sociodemographic and clinical characteristics of the enrolled patients

The analysis of the results showed that out of 149 patients, one hundred eighteen (79%) were female and 31 were male (21%); their mean age was 38.60 ± 8.03 (range, 18–60) years. The results of the comparison of baseline sociodemographic and clinical characteristics among the normal thyroid function group and different thyroid dysfunction groups are displayed in Table 1. The mean age, sex, marital status, educational status, cigarette smoking history, height, weight, waist circumference, and hip circumference did not differ among these subgroups.

Table 1

Sociodemographic and clinical characteristics of the study participants according to thyroid functional status
Parameters		All n = 149	Overt Hypothyroidism n = 24	Subclinical Hypothyroidism n = 39	Euthyroid subjects n = 86	P-value
Age, years, mean ± SD		38.6 ± 8.03	38.57 ± 8.46	37.18 ± 8.35	41 ± 5.16	0.181
Sex, male, n (%)		31(20.81%)	2(1.34%)	22(14.77%)	7(4.7%)	0.161
Marital status, married, n (%)		142(95.3%)	24(16.11%)	82(55.03%)	36(24.16%)	0.374
Educational status, n (%)	Illiterate	22(14.77%)	4(2.68%)	13(8.72%)	5(3.36%)	0.598
	Elementary	120(80.54%)	20(13.42%)	69(46.31%)	31(20.81%)
	Higher Education	7(4.7%)	0(0%)	4(2.68%)	3(2.01%)
Cigarette smoking history, n (%)		6(4.03%)	0(0%)	5(3.36%)	1(0.67%)	0.380
Water vaporizing smoke history, n (%)		30(20.13%)	5(3.36%)	13(8.72%)	12(8.05%)	0.129
Height (cm), mean ± SD		157.44 ± 8.13	159.56 ± 8.55	160.86 ± 8.73	158.09 ± 8.1	0.187
Weight (kg), mean ± SD		71.6 ± 10.19	70.71 ± 11.85	71.2 ± 12.09	69.13 ± 12.41	0.102
Waist circumference (cm), mean ± SD		90.75 ± 9.65	91.07 ± 9.93	91.3 ± 10.4	90.83 ± 9.52	0.618
Hip circumference (cm), mean ± SD		106.25 ± 8.96	103.93 ± 10.51	103.7 ± 11.23	102.8 ± 10.12	0.967
SD: Standard Deviation

Ultrasound features in relation to thyroid functional status

Ultrasound features of patients were classified based on echogenicity and nodularity of the thyroid parenchyma. The sizes of the right and left thyroid lobes and isthmus in terms of length, width, and anterior-posterior diameter were summarized and compared by the thyroid function status. The mean thyroid volume in the males in the study population was 13.58 ± 4.19 and in the females 10.44 ± 3.32 (P < 0.05). Echogenicity was recorded as isoechoic in 15 (10.07%) and hypoechoic in 119 subjects (79.87%). Nodular structures were detected in 54 (36.2%) patients, in whom 38 (25.5%) micronodular and 16 (10.7%) macronodular were detected. The length, width, thickness, and volume of the left and right thyroid lobes and total thyroid volume had also no difference among the study groups (P > 0.05). There was a significant difference in isthmus thickness between the study groups, where euthyroid ‎subjects had significantly thicker isthmus than overt and subclinical hypothyroid patients (p = 0.018). Also, the mean thyroid volume in the 149 subjects was 11.10 ± 3.73 ml. There were no statistically significant differences in the distribution of the nodule structures in the study groups (p = 0 > 05). According to the Sostre and Reyes gray-scale classification, thyroid glands were scored as Grade 0 in 28 patients, Grade 1 in 15 patients, Grade 2 in 89 patients, Grade 3 in 9 patients, and Grade 4 in 8 patients. There were no statistically significant differences in the distribution of nodular structures in the study groups (P = 0.116), as shown in Table 2.

Table 2. Ultrasound features of the study participants according to thyroid functional status

P value	Euthyroid subjects n= 86	Subclinical Hypothyroidism n= 39	Overt Hypothyroidism n= 24	All n= 149		Parameters
0.008	62(72.09%)	22(56.41%)	11(45.83%)	95(63.76%)	Without pseudonodule		Pseudonodule, n (%)
	20(23.26%)	12(30.77%)	6(25%)	38(25.5%)	Pseudomicro nodule
	4(4.65%)	5(12.82%)	7(29.17%)	16(10.74%)	Pseudomacro nodule
0.111	63(42.28%)	34(22.82%)	22(14.77%)	119(79.87%)	Hypoechoic		Echogenicity of parenchyma, n (%)
	9(6.04%)	0(0%)	2(1.34%)	11(7.38%)	Hyperechoic
	10(6.71%)	5(3.36%)	0(0%)	15(10.07%)	Isoechoic
0.785	6(6.98%)	4(10.26%)	2(8.33%)	12(8.05%)	Solid		Nodule Composition, n (%)
	1(1.16%)	0(0%)	1(4.17%)	2(1.34%)	Cystic
	3(3.49%)	1(2.56%)	0(0%)	4(2.68%)	Complex
0.864	10(11.63%)	6(15.38%)	4(16.67%)	20(13.42%)	Globular		Nodule Shape, n (%)
0.864	1(1.16%)	0(0%)	0(0%)	1(0.67%)	Irregular		Nodule Shape, n (%)
0.702	2(2.33%)	1(2.56%)	5(20.83%)	2(1.34%)	Reactive lymph node, n (%)
0.116	9(79.07%)	8(66.67%)	11(54.17%)	28(71.81%)	G0		Gray scale calcification, n (%)
	4(12.79%)	7(17.95%)	4(20.83%)	15(15.44%)	G1
	32(2.33%)	29(10.26%)	28(20.83%)	89(7.38%)	G2
	4(4.65%)	2(5.13%)	3(4.17%)	9(4.7%)	G3
	2(1.16%)	3(0%)	3(0%)	8(0.67%)	G4
0.132	15.14±3.03	14.8±2.94	15.04±3.1	15.72±3.72	thickness		Right lobe, mm, mean ± SD
0.961	17.06±3.3	17.23±2.75	17.21±2.97	17.4±3.26	width
0.055	45.28±3.59	46.67±2.89	46.11±3.13	45.49±2.85	length
0.478	5.53±2.2	7.27±5.88	6.25±4.01	5.68±2.2	Volume (ml)
0.544	14.46±2.88	14.03±3.02	14.3±3.02	15±3.24	thickness		Left lobe, mm, mean ± SD
0.354	16.67±3.26	16.96±2.67	16.9±2.98	17.08±3.64	width
0.844	44.9±3.43	45.07±3.6	44.87±3.57	44.08±3.72	length
0.486	4.67±1.6	5.25±3.21	5.13±2.52	5.48±2.52	Volume (ml)
0.018	2.26±1.2	1.77±0.74	1.91±0.9	1.86±0.68	Isthmus thickness, mm, mean ± SD

SD: Standard Deviation

Ultrasound features in relation to thyroid functional parameters and thyroid autoimmune antibodies

Figure 1 shows the changes in thyroid function test and level of thyroid autoimmune antibodies based on the ultrasonographic findings. In the baseline, the mean serum levels of thyroid hormones, anti-TPO and anti-Tg were compared more in the study groups. Serum TSH, anti-TPO and anti Tg titers were significantly higher in patients with hypoechogenicity than those with normal echogenicity (P = 0.018, P = 0. 035 and P = 0.014, respectively). Mean serum TSH was significantly higher in patients with macronodules than those with micronodules and subjects without nodules (P = 0.003). The means of serum anti-Tg and anti-TPO titers were significantly higher in patients with macronodules than those with micronodules and subjects without nodules (P < 0.05).

When we correlated the baseline sonographic finding to thyroid function test, anti-TPO and anti-Tg titers, there were significant correlations, as shown in Fig. 2. Isthmus thickness had a significant negative correlation with FT4 (P = 0.046; r = 0.11). FT3 had also a significant negative correlation with isthmus thickness (P = 0.017; r = 0.15). Anti-TPO titer had a significant positive correlation with the total volume (P = 0.011; r = 0.24). Anti-TPO titer had a significant positive correlation with the right lobe volume (P = 0.018; r = 0.2). Anti-Tg titer had a significant positive correlation with isthmus thickness (P = 0.006; r = 0.1). Anti-Tg titer had a significant positive correlation with left lobe volume (P = 0.012; r = 0.3). Also, it had a significant positive correlation with right lobe volume (P = 0.019; r = 0.31) and had a significant correlation with the total volume (P = 0.042; r = 0.32). The sonographic parameters examined in this study were reassigned to Sostre and Reyes Classification System. Most patients were in Grade 2 and then in Grade 0. There was a significant difference in serum anti-TPO titer among different thyroid grade scores. By increasing the grades, the anti-TPO titer significantly increased (P < 0.05).

In addition, we compared various groups with a view to detect significant differences in TSH, free T4 and free T3 concentration. According to Table 3, there were no significant differences between mentioned parameters.

Table 3

The result of the serum thyroid factors in different grades of thyroid ultrasonographic indexes (G0- G4)
Variables	G0	G1	G2	G3	G4	P-value
Serum free T4 (pmol/L)	13.42 ± 2.51	13.98 ± 4.07	13.87 ± 2.52	13.42 ± 2.59	14.22 ± 3.70	0.979
Serum free T3 (pmol/L)	4.25 ± 0.88	4.70 ± 2.06	4.11 ± 0.86	3.50 ± 1.52	3.28 ± 1.44	0.140
Serum TSH (mIU/mL)	4.76 ± 4.08	4.66 ± 4.41	5.24 ± 4.72	5.92 ± 2.98	5.18 ± 0.88	0.223
TPO-Ab titer (IU/mL)	206.59 ± 160.30	287.14 ± 145.75	285.82 ± 197.41	280.54 ± 238.48	335.70 ± 165.11	0.032
Tg-Ab titer (IU/mL)	677.04 ± 365.63	375.94 ± 458.87	755.77 ± 405.09	981.16 ± 722.38	1321.7 ± 769.01	0.301
TSH: thyroid stimulating hormone, Tg-Ab: anti-thyroglobulin antibody, TPO-Ab: anti-thyroid peroxidase antibody.

With the advent of more precise diagnostic tests, the diagnosis of Hashimoto's thyroiditis cannot be trusted merely on a single diagnostic procedure [11]. The histopathologic diagnosis of Hashimoto’s thyroiditis is made following the microscopic identification of chronic lymphocytic thyroiditis. However, as most patients do not undergo thyroidectomy, in the clinical setting, diagnosis is made through detection of elevated serum anti-TPO Ab and anti-Tg Ab [12]. When a patient presents with an undiagnosed thyroid pathologic condition, an ideal diagnostic test should ideally be able to suggest the presence of thyroid autoimmunity, distinguish it from other thyroid illnesses, to measure the size and shape of organs, detect the changes in size during follow-up, and provide information about disease activity. US of thyroid has considerable advantages, including its bedside availability, ease of use, and reproducibility; it has been proved to be very effective in the diagnostic approach to thyroid disorders [13]. Some US characteristics are associated with developing hypothyroidism. Most of the available data on diagnostic studies in the setting of Hashimoto’s thyroiditis come from those already receiving levothyroxine replacement therapy [14]. The purpose of this study was to evaluate the role of sonography in assessing inflammatory activity and predict functional disorders of a group of patients with Hashimoto's thyroiditis. We suggest that sonographic patterns that demonstrate the type and extent of structural changes of the thyroid in different levels of thyroid antibodies and thyroid function. Thyroid autoantibodies had positive significant correlations with different parameters of the thyroid volume (P < 0.05). The results of our study showed that increased thyroid volume was consistent with increasing anti-TPO titers. In general, the role of anti-TPO in the process of tissue destruction associated with hypothyroidism due to Hashimoto's thyroiditis has been proven, and its cytotoxic effects on the thyroid cells accelerate the thyroid dysfunction due to the complement fixation strength [5]. Besides, it has a higher pathological value than anti-Tg titer and is more specific and more valuable for the diagnosis of autoimmune thyroid disorders [15]. On the other hand, thyroid enlargement is due to inflammation and cell infiltration of the thyroid tissue during illness. Therefore, this study showed that increased thyroid volume was associated with higher anti-TPO titer. Hypoechogenecitis is a known phenomenon in the Hashimoto's thyroiditis. As previously mentioned, hypoechogenicity of the thyroid can be due to infiltration of the lymphocytic tissue. The decreased echogenicity of the thyroid can be due to a reduction in the content of the parenchymal thyroid colloid, an increase in the blood flow of the thyroid, or infiltration of the lymphocytic tissue [16]. Our study is in line with other studies, showing that the chances of developing hypoechogenicity increase significantly with increasing TSH, anti-Tg and anti-TPO levels [14]. Of the few studies that assessed the relationship between anti-Tg titer and hypoechogenicity, none has found any such association [17, 18]. It is still arguable whether all patients with autoimmune thyroid diseases are at increased risk for nodules and thyroid cancer or whether there are certain thyroid characteristics that increase this risk [19]. In our study, mean serum TSH, anti-Tg, and anti-TPO titers were significantly higher in patients with macronodules than those with micronodules and subjects without nodules. The formation of pseudonodules in the thyroid tissue can be commonly found in Hashimoto's thyroiditis. Due to the inflammation and infiltration of the immune cells in the thyroid tissue, the chance of forming the pseudonodules in the thyroid tissue increases. Infiltration of the immune cells follows an increase in the activity of the autoimmune system. Anti-TPO and anti-Tg antibodies play a role as an autoimmune specific marker, so obviously, the chance of nodularity of the parenchyma thyroid increases with the presence of an increase in the level of autoantibodies. Hypoechoic pseudonodular and multifocal lesions very likely represent the areas of high inflammatory activity and lymphocytic infiltration. Reduced echogenicity results in the reduction of colloid content, increased thyroid blood flow, or increased lymphocytic infiltration. Inflammatory status promotes the development of thyroid nodule, perhaps due to its indirect effect through hindering the synthesis of thyroid hormone, which results in the elevation of TSH [17]. Many thyroid growth-stimulatory factors, such as TSH, insulin-like growth factor-1 and fibroblast growth factor, might be involved in the development of adenomatous lesions in patients with Hashimoto’s thyroiditis [20, 21].

One hundred twenty-five (85.9%) patients in our study had subclinical hypothyroidism or euthyroid state. Subclinical hypothyroid patients with underlying thyroid disease have an increased risk of development to overt hypothyroidism, which is associated with adverse effects on lipid profile and cardiovascular function [22]. However, predicting disease progression and assessing the risk of evolution to a more severe form of thyroid dysfunction are challenging. In our study, based on the classification system published by Sostre and Reyes, the US pattern of the thyroid was found in most of our patients in the G2 class. Thus, most patients suffering from Hashimoto's thyroiditis had their sonographic thyroid pattern as multiple hypoechoic foci or patches scattered throughout an otherwise normoechoic gland, which is more indicative of focal rather than diffuse involvement. The G2 pattern is more likely to indicate mild to moderate thyroid involvement, which is more common in patients with more subclinical symptoms. Also, the results of the present study showed that with an increase in the anti-TPO titer, the odds of an US pattern in higher grades were higher. Anti-TPO antibody could cause defective thyroid organization and shifts the surface area of the thyroid structure and the sonographic pattern of the thyroid toward higher grades [23].

There were some limitations in this study; it used a cross-sectional design and included a relatively small number of participants who underwent US examinations at a single institution. Additionally, we did not conduct a follow-up ultrasonography of consecutive patients. A study with a larger sample size and follow up should be conducted to validate our results.

We conclude that the high level of anti-TPO may cause significant changes in the pattern of US thyroid markers, which can be attributed to the potential role of this autoantibody in defective thyroid organization. Therefore, the use of US with the review of the level of anti-TPO and anti-Tg in the detection and investigation of the severity and extent of the Hashimoto's conflict is very helpful and can help determine which patients in the future have a higher chance of developing hypothyroidism and need to be followed up regularly.

TPO: Thyroid peroxidase; Tg: Thyroglobulin; US: Ultrasonography; TSH: Thyroid stimulating hormone; FT4: free T4; FT3: free T3; lt: left; rt: right; V: Volume; Ab; Antibody; SD: Standard deviation.

Ethics approval and consent to participate

The local Ethics Committee and Vice-Chancellor of research at Shiraz University of Medical Sciences (SUMS) approved this study with the reference number of IR.SUMS.REC.1395.S161. All the patients and their parents signed a written informed consent form for participation in the study and any possible publication of their data, after explaining the aim, method and goal of the study for the participants.

Consent for publication

All the patients signed a written informed consent form for publication of any data from their results after a session of explaining the aim, method, and goal of the study for each participant.

Availability of data and materials

The datasets generated during and analyzed during the current study are not publicly available (due to protect the patient’s information), but are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests. Authors disclose all relationships or interests that could have direct or potential influence or impart bias on the work.

Funding

This study was supported by Shiraz University of Medical Sciences [IR.SUMS.REC.1395.S161].

Authors’ contributions

FE collaborated in methodology, investigation, writing, original draft preparation, conceptualization, review, and editing. GRO collaborated in software, data curation, and writing-preparation. MHD collaborated in the investigation, draft writing-review-editing, supervision, project administration, and funding acquisition. RS collaborated in the investigation, validation of data, and draft writing. MBK collaborated in the investigation, validation, software and formal analysis, and editing. MMD collaborated in conceptualization, draft preparation, and editing. MAB contributed to the investigation, analysis, review and editing. All authors read and approved the final manuscript.

Acknowledgements

The authors would like to thank Shiraz University of Medical Sciences, Shiraz, Iran and also Center for Development of Clinical Research of Nemazee Hospital and Dr. Nasrin Shokrpour for editorial assistance.

Kalantar K, Khansalar S, Eshkevar Vakili M, Ghasemi D, Dabbaghmanesh MH, Amirghofran Z. Association of Foxp3 gene variants with risk of Hashimoto’s thyroiditis and correlation with anti-tpo antibody levels. Acta Endocrinol (Copenh). 2019;15:423–9.
Ashouri E, Dabbaghmanesh MH, Ranjbar Omrani G. Presence of more activating KIR genes is associated with Hashimoto’s thyroiditis. Endocrine. 2014;46:519–25.
Seyyedi N, Dehbidi GR, Karimi M, Asgari A, Esmaeili B, Zare F, et al. Human herpesvirus 6A active infection in patients with autoimmune Hashimoto’s thyroiditis. Brazilian J Infect Dis. 2019;23:435–40.
Rostamzadeh D, Dabbaghmanesh MH, Shabani M, Hosseini A, Amirghofran Z. Expression Profile of Human Fc Receptor-Like 1, 2, and 4 Molecules in Peripheral Blood Mononuclear Cells of Patients with Hashimoto’s Thyroiditis and Graves' Disease. Horm Metab Res. 2015;47:693–8.
Fröhlich E, Wahl R. Thyroid autoimmunity: Role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Frontiers in Immunology. 2017;8:28–34.
Kosiak W, Piskunowicz M, Świętoń D, Batko T, Kaszubowski M. An additional ultrasonographic sign of Hashimoto’s lymphocytic thyroiditis in children. J Ultrason. 2015;15:349–57.
Guan H, De Morais NS, Stuart J, Ahmadi S, Marqusee E, Kim MI, et al. Discordance of serological and sonographic markers for Hashimoto’s thyroiditis with gold standard histopathology. Eur J Endocrinol. 2019;181:539–44.
Sostre S, Reyes MM. Sonographic diagnosis and grading of Hashimoto’s thyroiditis. J Endocrinol Invest. 1991;14:115–21.
Dabbaghmanesh MH, Sadegholvaad A, Zarei F, Omrani G. Zinc status and relation to thyroid hormone profile in Iranian schoolchildren. J Trop Pediatr. 2008;54:58–61.
Koohi Hosseinabadi O, Behnam MA, Khoradmehr A, Emami F, Sobhani Z, Dehghanian AR, et al. Benign prostatic hyperplasia treatment using plasmonic nanoparticles irradiated by laser in a rat model. Biomed Pharmacother. 2020;127:1–8.
Zhang Y, Jia DD, Zhang YF, Cheng MD, Zhu WX, Li PF, et al. The emerging function and clinical significance of circrnas in thyroid cancer and autoimmune thyroid diseases. Int J Bio Sci. 2021;17:1731–41.
Talattof Z, Dabbaghmanesh MH, Parvizi Y, Esnaashari N, Azad A. The Association between Burning Mouth Syndrome and Level of Thyroid Hormones in Hashimotos Thyroiditis in Public Hospitals in Shiraz, 2016. J Dent. 2019;20:42–7.
Trimboli P. Ultrasound: The extension of our hands to improve the management of thyroid patients. Cancers. 2021;13:1–2.
Jeong SH, Hong HS, Lee JY. The association between thyroid echogenicity and thyroid function in pediatric and adolescent Hashimoto’s thyroiditis. Medicine (Baltimore). 2019;98:150–55.
Mittal K, Rafiq MA, Rafiullah R, Harripaul R, Ali H, Ayaz M, et al. Mutations in the genes for thyroglobulin and thyroid peroxidase cause thyroid dyshormonogenesis and autosomal-recessive intellectual disability. J Hum Genet. 2016;61:867–72.
De Morais NS, Stuart J, Guan H, Wang Z, Cibas ES, Frates MC, et al. The impact of hashimoto thyroiditis on thyroid nodule cytology and risk of thyroid cancer. J Endocr Soc. 2019;3:791–00.
Schiemann U, Avenhaus W, Konturek J, Gellner R, Hengst K, Gross M. Relationship of clinical features and laboratory parameters to thyroid echogenicity measured by standardized grey scale ultrasonography in patients with Hashimoto’s thyroiditis. Med Sci Monit. 2003;9:123–40.
Mazziotti G, Sorvillo F, Iorio S, Carbone A, Romeo A, Piscopo M, et al. Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto’s thyroiditis. Clin Endocrinol (Oxf). 2003;59:223–9.
Słowińska-Klencka D, Wojtaszek-Nowicka M, Klencki M, Wysocka-Konieczna K, Popowicz B. The Presence of Hypoechoic Micronodules in Patients with Hashimoto′s Thyroiditis Increases the Risk of an Alarming Cytological Outcome. J Clin Med. 2021;10:638–45.
Smith TJ. Insulin-Like Growth Factor Pathway and the Thyroid. Front Endocrinol (Lausanne). 2021;12:372–90.
Ahn J, Moyers J, Wong J, Hsueh CT. Thyroid dysfunction from inhibitor of fibroblast growth factor receptor. Exp Hematol Oncol. 2019;8:25–33.
Papadopoulou AM, Bakogiannis N, Skrapari I, Moris D, Bakoyiannis C. Thyroid Dysfunction and Atherosclerosis: A Systematic Review. In Vivo. 2020;34:3127–36.
Weetman AP. An update on the pathogenesis of Hashimoto’s thyroiditis. J Endocrinological Invest. 2021;44:883–90.

No competing interests reported.

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Comparison of the sonography index of thyroid gland with serum level of Anti-thyroid peroxidase, Anti-thyroglobulin and thyroid function test in patients with Hashimoto thyroiditis

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Abstract

Background

Methods

Results

Conclusions

Trial registration:

Figures

Background

Methods

Study Design

Setting

Laboratory Tests

Ultrasonography

Data analysis

Results

Baseline sociodemographic and clinical characteristics of the enrolled patients

Ultrasound features in relation to thyroid functional status

Ultrasound features in relation to thyroid functional parameters and thyroid autoimmune antibodies

Discussion

Conclusions

Abbreviations

Declarations

References

Competing Interests

Status:

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