Original Investigation

Evaluation of Salivary Glands by Ultrasonography and Inflammatory Markers in Children with Autoimmune Thyroiditis


  • Sevgi Demiröz Taşolar
  • Ahmet Sığırcı
  • Nurdan Çiftçi
  • Aslınur Cengiz
  • Güleç Mert Doğan
  • Ayşehan Akıncı

Received Date: 19.06.2023 Accepted Date: 23.07.2023 İstanbul Med J 2023;24(3):246-250


Although more common in adults, autoimmune thyroiditis (AT) is one of the most common thyroid diseases in children and adolescents. Salivary gland involvement has been described in many studies of patients with AT. Several inflammatory scores are used to assess the inflammatory status of patients with systemic autoimmune diseases. We aimed to sonographically evaluate the parotid and submandibular salivary glands with inflammatory parameters in patients with AT in our study.


Our study population consisted of 37 consecutive pediatric AT patients and 29 healthy control subjects. Ultrasonographic and laboratory evaluations of the study population were performed. Jamovi and MedCalc software were used to analyze the data.


The volume of the thyroid gland in the patients was significantly higher than that in the control group (p=0.030), while there was no difference in the volume of the salivary glands. Multiple logistic regression analysis was planned to assess the predictability of salivary gland involvement in patients with the disease. Both systemic immune-inflammation index (SII) and pan-immune inflammation value (PIV) were found to be predictors of salivary gland involvement in AT patients.


We found that both SII and PIV inflammatory markers are predictive of salivary gland parenchymal changes in patients with AT, and SII is likely to be more valuable than PIV at this time.

Keywords: Autoimmune thyroiditis, gland, parotid, submandibular, SII, PIV


Autoimmune thyroiditis (AT) is the most common disease of the thyroid gland in the pediatric age group. Although a combination of genetic, environmental, and immune factors are thought to play a role, the exact cause of AT is not fully understood. While AT can occur at any age, including pediatric age, the mechanisms underlying its development in children are similar to those in adults. AT can occur on its own or can be associated with other autoimmune diseases. The combination of AT with specific autoimmune disorders is known as autoimmune polyglandular syndromes (1,2). However, in some cases, there can be associated to the involvement of the salivary glands. The involvement of the salivary glands in AT is relatively rare but has been the subject of reports in the literature (3-5). However, as far as we know, salivary glands in patients with AT have not been sonographically evaluated in the literature.

Ultrasound (US) is an excellent choice for the initial evaluation of the salivary gland in pediatric patients and is an easily accessible and non-invasive method for evaluating superficial structures with good resolution. It is the first choice for pediatric patients as it does not contain the radiation. Normal submandibular and parotitis glands have homogeneous parenchyma on US and are hyperechoic compared to adjacent muscles, and the degree of echogenicity may vary in proportion to the amount of glandular adipose tissue (6).

In recent years, several leukocyte-based inflammatory markers have been identified that can provide valuable insight into an individual’s inflammatory status, including the systemic immune-inflammation index (SII), monocyte/high-density lipoprotein ratio, platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio, neutrophil/lymphocyte ratio (NLR) and pan-immune value (PIV). There is evidence that these inflammatory markers may also be useful in assessing the inflammatory status of patients with systemic autoimmune diseases (7-9).

No US-based study has been conducted on parotid and submandibular gland involvement in AT disease in pediatric patients. The main objective of this study was to evaluate parotid and submandibular gland parenchyma in patients with AT using US and inflammatory parameters.


The study participants consisted of patients followed up with a diagnosis of AT in the pediatric endocrinology clinic and a control group. Consecutive patients with AT who were under 18 years of age and had parental consent were eligible for inclusion in the study. AT was diagnosed using radioimmunoassay results for anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (ATG), and thyroid-stimulating hormone (TSH). The control group consisted of participants who were examined with neck US for any reason and whose thyroid function tests (TFT) and TSH values were normal for the last 1 month. Patients who had another systemic disease and were receiving drug therapy were excluded from the study. The study was conducted in accordance with the Declaration of Helsinki and the guidelines for good clinical practice. The study was approved by the İnönü University Scientific Research and Publication Ethics Committee (approval number: 2020/491, date: 17.03.2020).

Ultrasonographic Evaluation

US was examined with a Logiq s8 (GE healthcare, USA) device using a linear probe with a frequency of 14 MHz. US was performed on all participants by the same pediatric radiologist unaware of their clinical and biochemical status. In the US examination, parenchyma echo structures and dimensions of the thyroid gland, submandibular gland, and parotid gland were evaluated with gray scale. Vascularity of the thyroid gland, submandibular gland, and parotid gland was evaluated subjectively with Doppler US. The thyroid gland was evaluated in the supine position and the neck in extension. The gain settings of the US scanner were adjusted so that the lumens of the carotid artery and internal jugular vein were echo-free. Normal thyroid parenchyma was defined as homogeneous and relative hyperechogenicity compared with adjacent muscle tissue. On gray scale US, abnormal parenchymal features of the thyroid gland were evaluated as heterogeneous echo and/or hypoechoic areas.

For each thyroid lobe, the mediolateral length (MLL) and the anteroposterior length (APL) were measured in the axial section and the inferior superior length (ISL) in the sagittal axis. The volume of each lobe was estimated using a standard geometric formula of APL x MLL x ISL x 0.523. The volume of the whole thyroid gland was calculated as the sum of the two lobes.

The submandibular glands were evaluated by US with the patient’s head slightly raised and the parotid gland in the supine position with the patient’s head facing the contralateral side. Each salivary gland size was evaluated for its echogenicity in at least two perpendicular planes. For each gland, MLL and APL were measured in the axial section and ISL in the sagittal axis. The standard geometric formula APL x MLL x ISL x 0.523 was used to estimate the volume of each gland. Gland volume was calculated as the average of both gland volumes. In the gray scale US, coarse echoes and hypoechoic areas in the gland parenchyma were considered abnormal parenchymal features (Figure 1).

Laboratory Evaluation

The results of complete blood count and TFT were obtained from the files of patients who were examined in the pediatric endocrine clinic. Two biomarkers of inflammation were calculated using the following formulae:

SII = platelet count x neutrophil count/lymphocyte count (10),

PIV = platelet count x neutrophil count x monocyte count/lymphocyte count (11).

Statistical Analysis

Jamovi (version 2.3.28) and MedCalc (version 20.027) software were used to analyze the data. The Kolmogorov-Smirnov test was used for the data distribution. Student’s t-test or Mann-Whitney U test was used for continuous variables and chi-square test for categorical variables, depending on the distribution of the data. Multiple logistic regression analysis was used to assess the salivary gland involvement. Age, sex, SII, and PIV parameters were included as univariate parameters in the regression analysis. Since SII and PIV parameters are obtained from similar variables, two modeling (for PIV and SII) were performed to avoid multicollinearity. Pairwise receiver operating characteristic (ROC) analysis was used to compare the two models [area under the curve (AUC), Youden index]. P-value <0.05 was considered statistically significant.


The demographics of the study population are shown in Table 1. There were no statistical differences between the groups for age, sex, and laboratory parameters (p>0.05, for all).

The ultrasonographic findings of the thyroid and salivary glands of the patients and the control group are given in Table 2. While the volume of the thyroid gland was significantly higher in the patients than in the control group (p=0.030), there was no difference in the volume of the salivary glands. However, salivary gland parenchyma involvement and vascularity in the patient group were significantly different from those in the control group.

Multiple logistic regression analysis was used to evaluate the predictability of salivary gland involvement in patients with the disease. To avoid multicollinearity in the analysis, two models were performed (for model 1: SII, model: 2 for PIV). In the analysis, SII [odds ratio (OR): 1.002, p=0.046] value was found to be significant in predicting salivary gland involvement in model I, and PIV (OR: 1.002, p=0.040) value was also found to be an independent predictor of salivary gland involvement in model 2. Pairwise ROC analysis was performed to compare both parameters in predicting the salivary gland involvement. In the analysis, although SII gave a higher AUC value, there was no statistical difference in terms of both parameters (Figure 2).


The main findings of our study were: (i) salivary gland parenchymal changes were significantly higher in patients with AT than in the control group, but there was no difference in salivary gland volumes; (ii) salivary gland involvement could be predicted by SII and PIV parameters in the regression analysis for salivary gland involvement; (iii) when comparing both parameters, there was no statistical difference in the pairwise ROC analysis. The disease, which is more common in women even before puberty, can result from defects in immune regulation or lymphocyte infiltration of the thyroid. In the majority of patients, antibodies (abs) can be detected against various thyroid-specific antigens. Whether antibody-mediated immune mechanisms contribute to the onset, progression, or pathogenesis of AT remains unclear. Anti-TPO and ATG are diagnostic markers of the underlying autoimmune destruction of the thyroid gland and are also found in the majority of patients (12).

The thyroid gland is histologically similar to the lacrimal and salivary glands. Studies of salivary gland involvement in people with AT have suggested that common mechanisms may be at work in the development of thyroiditis and salivary gland immune disease (5,13-15). It has been shown that an immunological imbalance in the salivary glands leads to secretory dysfunction not only in Sjögren’s syndrome (SS) but also in other autoimmune diseases such as psoriasis (16), rheumatoid arthritis (17) and systemic sclerosis (18). Genetic and immunopathological similarity between SS and AT (19-21) has been reported. In previous studies, it was determined that the prevalence of AT in patients with primary SS increased compared with the normal population (5). In another study, it was confirmed that patients with euthyroid AT had increased oxidative modification of both the parotid and submandibular glands and that this was associated with autoimmunity (3).

Animal studies have shown that thyroid dysfunction can affect the secretory unit of the salivary gland (22). The secretory function of the submandibular glands is impaired in patients with AT, as shown by Agha-Hosseini et al (23). Syed et al. (24) showed that there may be significant involvement of the salivary glands in AT cases, that there is a significant decrease in sialometric values in AT patients, and that AT may be the cause of hyposalivation.

Rubaltelli et al. (25) and Nozaki et al. (26) stated that the hypoechoic area is a specific finding in chronic recurrent parotitis and patients with SS. Parenchymal heterogeneity was also noted as another finding. hypoechoic areas on sonograms correlate with findings on sialograms and that US may play an important role in diagnosis.

There is also evidence that hypoechoic areas are not only a sign of peripheral sialectasis but also of lymphocytic infiltration around the ducts (27), and argued that symographic changes could be verified more precisely than sialography. US is very sensitive in the detection of inflammatory changes in the salivary glands but has a lower degree of specificity. We observed that the parenchyma echo changes observed in the US evaluation of the submandibular and parotid glands, which were shown to be functionally affected in AT in previous studies, differed significantly compared with the control group. Although it is known that the echo structure of normal glands in children may vary according to the age and structure of the children, our data on a similar age range in the control group suggest that our findings are not related to the age of the children. In addition, patients with CBC and clinical signs of infection were not included to rule out infectious causes, which are common causes of parenchymal changes. We did not observe a significant difference in Doppler US between the patients and the control group. We believe that quantitative and advanced imaging techniques are required to assess glandular vascularity.

Systemic subclinical inflammation is the cause of comorbidities in children and adults (28,29). While there was no difference in NLR between patients with differentiated thyroid cancer and patients with benign thyroid nodules (30), higher values were associated with tumor size, invasion, and metastasis (31). In other studies, it has been shown that NLR and PLR values are higher in patients with Hashimoto’s thyroiditis (32-34). Another study showed that obesity-induced thyroid dysfunction may be associated with inflammatory markers (NLR, PLR, and SII) (35). It has previously been shown that SII can be used in patients with subacute thyroiditis in the diagnosis and follow-up (36,37). In our study, we investigated SII and PIV values as parameters that can predict the salivary gland involvement in children with thyroiditis. We found that both were predictors of salivary gland involvement in children with thyroiditis. In addition, when both parameters were compared using pairwise ROC analysis although the AUC value of the SII parameter was higher, there was no statistical difference. We believe that salivary gland involvement in children with thyroiditis can be predicted from these parameters, which are used as indicators of acute inflammation.

Study Limitations

The main limitations of our study are its single-centre nature, a small number of patients, and cross-sectional design. One of the limitations of our study is that due to its routine use in our clinic, gray scale US and Doppler US were used and no quantitative evaluation was performed. Further studies with advanced US imaging methods are needed.


In our study, we observed that there may be salivary gland parenchymal changes in patients with AT, and SII and PIV inflammatory markers predict these changes, and at this point, the SII value may be more valuable than the PIV value. There is a need for large-scale studies to clarify this issue.

Ethics Committee Approval: The study was approved by the İnönü University Scientific Research and Publication Ethics Committee (approval number: 2020/491, date: 17.03.2020).

Informed Consent: It was obtained.

Peer-review: Externally peer-reviewed.

Authorship Contributions: Surgical and Medical Practices - S.D.T., A.S., N.Ç., A.C., G.M.D., A.A.; Concept - S.D.T., A.S., N.Ç., A.C., G.M.D., A.A.; Design - S.D.T., A.S., N.Ç., A.A.; Data Collection or Processing - S.D.T., A.S., N.Ç., A.C., G.M.D., A.A.; Analysis or Interpretation - S.D.T., A.S., A.C., G.M.D.; Literature Search - S.D.T., A.S., A.C., G.M.D.; Writing - S.D.T., A.S.

Conflict of Interest: No conflict of interest was declared by the authors.

Financial Disclosure: The authors declared that this study received no financial support.


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