Our study revealed that greater thyroid dysfunction severity was associated with higher US grade in child and adolescent AITD patients. TSH level also differed significantly according to US grade.
AITD is the most common cause of thyroid dysfunction in children and adolescents in iodine-sufficient populations, and its representative diseases are HT and GD13. HT and GD are the most common causes of hypothyroidism and hyperthyroidism, respectively4,10,13,15−18. HT, i.e., lymphocytic thyroiditis, is a goitrous form of AITD. In HT, autoantibodies break down thyroid gland cells during immune processes15–17. GD is caused by thyroid gland stimulation by autoantibodies against the TSH receptor on follicular epithelial cells18. These antibodies mimic the effects of TSH, causing overproduction and release of thyroid hormone. The typical HT histological features include lymphoplasmacytic infiltration, germinal center formation, follicular destruction, Hurthle cell change, and varying degrees of fibrosis9,10,16, while GD is characterized by histopathological hypercellularity, patchy lymphocyte infiltration, little colloid, and scalloping colloid19.
US is a diagnostic tool that is widely used as an adjunct to clinical exams for evaluating thyroid size, anatomy, and parenchymal abnormalities2,12. On US, healthy thyroid gland echogenicity is homogeneous and higher than that of the surrounding muscle20. AITD patients’ thyroids present differently, with characteristic US findings such as variable degrees of thyroid gland enlargement, decreased parenchymal echogenicity, and heterogeneous parenchymal echo pattern. Thyroid gland enlargement is usually diffuse and symmetric. HT may show as poorly defined, patchy hypoechoic areas and micronodular patterns consisting of multiple small (~ 2–6 mm) hypoechoic nodules. In GD, vascularity tends to be increased, while in HT, it is variable21.
Tissue echogenicity of the thyroid gland on US depends on the organ’s cellularity and vascularization. Decreased colloid content, lymphocytic infiltration, and increases in intrathyroidal flow result in hypoechoic tissue patterns20,22,23. As mentioned above, inflammatory cells infiltrate and destroy the thyroid gland in HT and GD, which can appear as hypoechogenicity on US.
Heterogeneous echogenicity of the thyroid gland is another well-known finding in AITD24–27. Heterogeneous echogenicity is caused by multiple structures of different acoustic impedances creating variable echogenicity degrees on US, and the normal representative tissue is muscle28. When healthy, organs such as the thyroid gland or liver consist of characteristic cells with little variation, thus showing homogenous echogenicity on US28. Considering the pathological findings of AITD, heterogeneity may also appear on US due to infiltration of other cells in the thyroid gland and fibrosis. Although heterogeneity is a well-known finding in AITD, no studies have evaluated the relationship between thyroid dysfunction severity and heterogenicity degree on US.
Thyroid dysfunction can affect child and adolescent growth and development in various ways. Overt hypothyroidism can cause a potentially fatal medical condition with adverse effects on lipid metabolism and cardiovascular function that occurs in about 10% of HT patients. Onset of this condition is insidious and it may not become clinically apparent until symptoms are abundantly developed35. Overt hyperthyroidism in children and adolescents is both less common and more severe than in adults29,30. Symptoms of hyperthyroidism include impaired neurodevelopmental outcomes and altered skeletal maturation28, such as craniosynostosis and advanced bone age in younger children. Additionally, for school-aged children, poor school performance is common, and may cause severe anxiety in patients and their parents31.
AITD, a single disease entity, can manifest in various thyroid function statuses. While subclinical and overt hypo- and hyperthyroidism share similar etiologies, the symptoms of the former are nonspecific and signs are typically absent32. Therefore, diagnosis and treatment decisions for subclinical hypo- and hyperthyroidism mainly depend on TFT results32–34. Subclinical thyroid dysfunction tends to develop into overt thyroid dysfunction32,33, and the risk of progression to overt hypothyroidism in subclinical hypothyroid patients is higher in patients with underlying thyroid disease12. It is difficult to predict the risk of progression to a more severe state of thyroid dysfunction. There is no agreement on clinical features, numerical values that indicate mild thyroid dysfunction, or prognosis10,12,32−24. In our study, there was an association between US grade and TSH level, which was consistent with results from a previous study35, where younger patients showed a stronger association between decreased echogenicity and higher TSH, and the relationship was stronger when the changes were recent. Hypoechogenicity of the thyroid gland is a common finding in HT. Jeong et al10, reported that the severity of HT varies depending on hypoechogenicity degree. Other studies have reported that changes in US may be an early sign of more severe thyroid dysfunction and initial hypoechogenicity indicates later development of hypothyroidism4.9. Those studies focused on adults and mainly dealt with HT. Our study findings indicate that hypoechogenicity and heterogeneity degree on US are correlated with thyroid dysfunction in child and adolescent AITD patients, including those with GD and HT.
In 11 patients in our study, thyroid function status changed in in a positive relationship with US grade, regardless of whether US grade worsened or improved. This is the first reported finding of not only exacerbation but also remission on US, and it suggests that US changes can reflect thyroid dysfunction status with high sensitivity.
We found no significant associations between echogenicity and TPOAb and TRAb levels. A few studies have assessed the correlation between autoantibody level and hypoechogenicity of the thyroid gland, but none found a significant relationship9,36. However, in mild thyroid dysfunction cases, checking the initial TPOAb level early with US can help predict the course of disease and set the treatment direction34.