Changes in the thymus gland with age: A sonographic evaluation

Abstract

Background:

Ultrasound evaluation of normal, ectopic, asymmetric, and hyperplastic thymus and also its differentiation from abnormalities are challenging in children, and few studies have addressed this issue. This study aimed to investigate the thymus sonographic changes with age.

Methods:

In this cross-sectional study, 118 healthy children were categorised into six age groups. Sonographic features of the thymus, including volume, anatomical position, symmetry, and echo-texture, were recorded.

Results:

The thymus was visible at all ages from the suprasternal view. In 77.5% of participants, the thymus gland volume in lobes was symmetrical; however, left (21.2%) and right (1.3%) predominance were also found. The most common position of the thymus was in front of the great vessels (100%) with suprasternal extension (97.5%). The mean volume of thymus was 21.3 ± 10.5 (mm). There was no significant difference in the volumes of the thymus between different age groups. The predominant echo-texture of the thymus in different age groups was hypoechoic with thin echogenic septa (liver-like) in below 2–3 years of age, the appearance of echogenic foci and hyperechoic echo-texture (liver-like with starry sky) in 2–14 years, and uniform hyperechoic echo-texture (fatty liver-like) or geographic echo-texture with coarse reticular pattern in above 14 years.

Conclusion:

In children, the thymus gland is visible in ultrasound examination in all age groups from the suprasternal view; however, the echo-texture of the normal thymus changes with age. There was no significant correlation between age and sex with total thymic volume. The specificity of these appearances has made ultrasound a problem-solving modality in children.

Introduction

The thymus is an endocrine gland of the mediastinum region, with the main function of T-cell maturation. It is an encapsulated organ composed of two lobes that are positioned anterior to the great vessels and posterior to the sternum.^1,2 The thymus continues to grow after birth and reaches its maximum size during puberty, weighing 20–50 g. The gland begins to lose mass after puberty, during thymic involution, as fat cells begin to occupy more of the gland’s tissue and replace the thymic tissue. This is continued into adolescence until the mass is reduced to 5–15 g. ³

Even physiologic stress can affect the thymus gland in significant ways. Following stress, for example, chemotherapy, the gland may grow in size, even greater than the normal values, as thymic rebound hyperplasia occurs.^4,5 These complex physiologic alterations of the thymus introduce a major challenge for interpreting X-ray observations of the gland, as the normal appearance of the thymus can vary greatly even in the same individuals; this may lead to false diagnoses of the thymic, mediastinal, cardiac, and lung diseases or unnecessary interventions. Although the thymus gland is observable in radiography or even computed tomography (CT) scans, it is not clearly distinguishable from cardiac lesions or mediastinal and lung tumors in these modalities.^6,7

All the while, ultrasound seems to be the preferred modality in evaluating thymic tissue. ⁸ In ultrasound, during infancy, thymic tissue demonstrates a similar echogenicity to hepatic tissue but less echogenic than muscle tissue. There are several echogenic regions observable within its uniform pattern. These hyperechoic regions resemble the ‘starry sky’ appearance of liver parenchyma and aid in identifying the thymic tissue. Ultrasound can also help determine the solid or cystic nature of the thymic and mediastinal lesions or find fatty deposits and calcifications within the thymus.^9,10 These, along with the availability and low cost of ultrasound, render it a suitable baseline diagnostic measure for thymic pathologies.

Radiologists thus have a significant role in differentiating normal thymic appearances and non-neoplastic thymic lesions. Therefore, preventing unnecessary interventions, biopsies, or even thymectomies depends on their knowledge of the normal appearance of the thymus and its normal variations. ¹¹ Few studies have tried to describe the most common ultrasound findings of the thymus. We aimed to investigate the sonographic changes of the thymus gland during childhood.

Methods

Study settings and approval

This cross-sectional observational study was carried out on the patients referring to the outpatient radiology department during 2019 and 2022. Before recruiting the participants, the extent of evaluations was described to the patients and their parents, and their informed consent was obtained. The anonymity of the participants was ensured by assigning sequential numbers to the collected data, while the patients understood that they were allowed to leave the study at any time. The Ethics Committee of Mashhad University of Medical Sciences approved this study with the approval code of IR.MUMS.MEDICAL.REC.1399.655.

Participants

The healthy children referring for ultrasound examination for any reason, such as renal colic follow-up, were recruited in this study using convenient sampling. The inclusion criteria were: the absence of significant medical conditions (such as chronic, inflammatory, and infectious diseases) and providing informed consent by subjects and their parents. Subjects who did not meet the inclusion criteria or had any illness or congenital anomalies of the thoracic region that might have affected ultrasound findings were excluded from the study.

Data collection

All participants underwent ultrasound scans of the neck region by an experienced radiologist, who examined their thymus gland using a MyLab class C (Esaote, Italy) scanner incorporating 7.5–12 MHz linear and 2.5–5 MHz curved probes. The participants’ demographic data (weight, age, and gender) were recorded. The documented ultrasound findings included width, anteroposterior dimension, volume, state of symmetry, position, and echogenicity of the thymus gland. The participants were categorised based on National Institute of Child Health and Human Development (NICHD) into six age groups: neonate (under 1 month), infant (1 month to 1 year), toddler (1–2 years), early childhood (2–5 years), late childhood (6–12 years), and adolescent (12–18 years). ¹²

Thymic lobes’ diameters were measured by locating the probe transversely on manubriosternal cartilage and sagittaly on the parasternal region. Trans-sternal and parasternal windows have been used to measure the transverse and anteroposterior (AP) diameters. These were standardised using the maximum thymic bulk in available windows. The thymic lobe volumes were measured by multiplying three dimensions divided by 2 (AP × CC (cranio-caudal) × width/2) and the isthmus volume was measured by multiplying three dimensions.

Statistical analysis

The data were analyzed using the IBM SPSS Statistics for Windows, version 23 (IBM Corp., Armonk, NY, USA). Kolmogorov–Smirnov test was used to assess the normal distribution of the data. Quantitative variables were described using the mean and standard deviation of parameters. The data were compared between groups using Mann–Whitney and Kruskal–Wallis tests. Pearson correlation test was used to assess the correlation between quantitative variables. p < 0.05 was considered statistically significant in all of the assessments.

Results

Overall, 118 individuals (61 males and 57 females) with a mean age of 5.11 ± 4.61 years were evaluated.

Acoustic window and observability

Figures 1 and 2 show the parasternal and the suprasternal views in all age groups. Figure 3 also shows transducer placement for the measurement of the thymic diameters. In all participants of any age, the thymus was observable in the suprasternal view. In children under 10, the thymus was observable from all four windows: suprasternal, left parasternal, right parasternal, and trans-sternal (manubriosternal joint cartilage). In girls under 10 and boys under 12 years old, the manubriosternal joint cartilage, with a width of 4–8 mm, was a suitable window for observing the isthmus. In children until 14 years of age, the thymus was observable from the suprasternal, left parasternal, and right parasternal windows in the supine position. In subjects older than 14, lateral and oblique views were required for observing the thymus.

Figure 1.

The thymus view from the trans-sternal and the parasternal window in different age groups.

Figure 2.

The thymus view from the suprasternal window in different age groups.

Figure 3.

Transducer placement for the measurement of the thymic diameters. (a) Trans-sternal (manobriosternal cartilage) view, (b) parasternal view, and (c) transverse suprasternal view with caudal tilting.

Symmetry and anatomic position

The thymus gland was symmetrical in 77.5% of the subjects. Of the remaining asymmetrical findings, 21.2% demonstrated left prominence and only 1.3% had a right prominence. The most commonly observed site was anterior to the great vessels (100%). In 97.5% of the participants, the thymus was extended to the suprasternal area. Other observed positions for the thymus included neck extension adjacent to the thyroid (53.1%) and paracardiac extension (34.4%).

Size and volume

The average volume of the right lobe, left lobe, and isthmus was 7.0 ± 4.4, 10.3 ± 6.4, and 4.1 ± 2.9 mL, respectively. The mean total volume of the thymus gland was also measured to be 21.3 ± 10.5 mL.

Table 1 shows the mean volume and diameter of the thymic lobes in different age groups. The analysis of variance (ANOVA) test did not demonstrate a significant difference in the total or lobar volumes across the age groups (p > 0.05). The thymus volumes were also compared across genders. According to the Mann–Whitney test, the differences between genders in the total thymus, left lobe, and isthmus volumes were insignificant (p > 0.05); however, the right lobe volume, right lobe cranio-caudal diameter, and left lobe width were found to be significantly larger in males (p < 0.05). Also, the Pearson test was unable to show a significant relationship between thymus volumes and age.

Table 1.

Comparison of the thymic lobe diameters and volumes between age groups.

	Neonate	Infant	Toddler	Early child	Late child	Adolescent	p*
Right lobe AP (mm)	20.3 ± 5.4	22.6 ± 6.2	22.5 ± 7.2	21.7 ± 7.7	19.6 ± 7.0	19.8 ± 7.3	0.571
Right lobe CC (mm)	46.0 ± 14.8	47.1 ± 11.7	46.0 ± 8.4	48.0 ± 11.9	43.5 ± 11.3	49.4 ± 11.5	0.622
Right lobe width (mm)	13.4 ± 4.5	13.3 ± 3.4	12.5 ± 5.4	15.4 ± 4.2	12.2 ± 2.9	12.0 ± 3.5	0.045
Left lobe AP (mm)	23.6 ± 4.2	25.8 ± 5.3	22.4 ± 9.4	24.1 ± 6.8	22.4 ± 8.0	19.5 ± 7.9	0.141
Left lobe CC (mm)	50.1 ± 9.0	54.5 ± 8.4	53.8 ± 7.0	56.8 ± 10.3	55.4 ± 10.4	56.8 ± 14.8	0.565
Left lobe width (mm)	15.1 ± 3.3	17.2 ± 5.2	15.5 ± 4.5	15.7 ± 4.8	14.0 ± 4.2	11.9 ± 3.5	0.011
Isthmus AP (mm)	10.6 ± 2.6	13.0 ± 4.2	9.8 ± 3.7	10.2 ± 8.1	8.7 ± 2.3	8.5 ± 3.0	0.015
Isthmus width (mm)	13.6 ± 3.3	20.0 ± 7.9	20.7 ± 7.4	24.1 ± 8.5	26.8 ± 11.1	33.0 ± 6.5	0.000
Right lobe (ml)	7.3 ± 5.5	7.5 ± 3.6	7.3 ± 5.8	8.4 ± 4.6	5.8 ± 3.7	7.0 ± 5.3	0.416
Left lobe (ml)	9.3 ± 4.4	12.5 ± 5.9	10.5 ± 8.5	11.8 ± 7.2	9.1 ± 5.7	8.5 ± 7.2	0.225
Isthmus (ml)	1.7 ± 0.7	4.4 ± 3.1	3.3 ± 3.0	3.8 ± 1.9	4.2 ± 2.9	5.9 ± 3.6	0.016
Total (ml)	18.1 ± 8.7	24.5 ± 8.6	21.2 ± 16.4	24.0 ± 10.6	18.9 ± 8.8	20.3 ± 13.7	0.250

CC: cranio-caudal diameter; AP: anteroposterior diameter; mm: millimeter; ml: milliliter.

Echo-texture

The four parenchymal echo-texture observed in this study were as follows (Figures 1 and 2):

1. Hypoechoic echo-texture and thin echogenic septa (liver like):

   • • In subjects until 2–3 years of age, the thymus demonstrated a hypoechoic pattern containing thin echogenic blades measuring 10 mm in length. The hypoechoic pattern included a thin echogenic septum, resembling hepatic tissue.
2. Appearance of echogenic foci (liver like with starry sky):

   • • In children above 2–3 years of age, echogenic foci (probably Calcified Hassall corpuscles) appeared in the parenchyma. With the increase in age, these echogenic foci had filled the entire parenchyma, forming a hyperechoic echo-texture. Due to the heterogeneous distribution of these foci, mixed hypo/hyperechoic echo-texture was a usual finding. This was the predominant pattern in boys aged 2–14 and girls aged 3–10 years. This pattern was also observable in some older children.
3. Geographic echo-texture:

   • • In some adolescents, the thymus gland is composed of mixed hyperechoic and hypoechoic areas due to geographic fatty infiltration. That is often associated with coarse reticular pattern.
4. Uniform hyperechoic echo-texture (fatty liver like):

   • • In subjects older than 10–14 years, the thymus gland mostly demonstrated a uniform hyperechoic pattern similar to that of the fatty liver or the parotid gland. This hyperechogenicity was observable in the suprasternal notch. However, likely due to sound attenuation, the thymus was less echogenic in the parasternal windows.

Although these echo patterns are predominant in specific age groups, each of these patterns may also be seen in other age groups.

Discussion

The thymus gland undergoes various changes in size and shape due to physiologic and pathologic factors, making the evaluation of its state extremely challenging. Previous studies have reported patients with ectopic thymus, cervical mass adjacent to the parotid gland, retro-thyroid, intrathyroid, unilateral mediastinal mass, and unilateral wedge-shaped lung opacity, all of which were associated with distinct clinical or radiologic diagnoses. In addition, normal hyperplasia of the thymus may simulate mediastinal mass, mediastinal widening, lobar pneumonia, and cardiomegaly (Figure 4). Previous studies have suggested ultrasound as a capable modality in assessing the thymus, readily available with no ionising radiation.^13–15

Figure 4.

Some patients with unusual ectopic thymus who were associated with a diagnostic problem. (a) Absence of thymus in anterior mediastinum, (b) ectopic thymus adjacent to parotid gland, (c) ectopic thymus anterior to thyroid gland, and (d) intrathyroid thymus (simulate PTC), and (e and f) two cases with asymmetric thymus and unilateral right lobe hyperplasia were presented with mediastinum mass and lung opacity on chest X-ray.

m: manubrium; p: parotid; t: thyroid.

Few studies have reported ultrasonographic measurements of the thymus in infants and children up to the age of eight.^13,14,16 In this study, we have done ultrasound examination of the thymus gland in healthy individuals in different age groups to assess its different characteristics such as size, position, symmetry, and echo pattern. A wide range of healthy subjects were examined in order to assess normal ultrasound findings of the thymus and its variations in different age groups.

According to the results of this study, the thymus can be examined at all ages from suprasternal windows. Parasternal and trans-sternal views in supine or oblique positions were the accessible windows.

In our study, in children aged less than 2–3 years, the ultrasonographic view of the thymus showed a uniform hypoechoic pattern containing thin echogenic regions that resembled hepatic tissues. In a report on 56 infants under 10 months, Han et al. compared the ultrasound appearance of the thymus in normal subjects with that of the liver, spleen, and thyroid gland. They found the echogenicity of the thymus to be less than the thyroid gland, liver, and spleen in most cases. The echogenicity of the thymus was reported to be homogeneous in 80% of the subjects, similar to the liver and spleen. ¹⁷ The echoic pattern we observed in children under the age of 2–3 years was in line with the findings of the above mentioned study.

Similarly, Nasseri and Eftekhari ¹¹ reported the ‘starry sky’ view of the normal thymus. In our study, in children above the age of 2–3 years, echogenic foci appeared in the parenchyma. With the increase of age, these echogenic foci had filled the entire parenchyma, forming a hyperechoic echo-texture. Since these foci distribution was not uniform, mixed hypo/hyperechoic echo-texture was a usual finding. This was the predominant pattern in boys aged 2–14 and girls aged 3–10 years. In some cases this pattern was observable in older children.

Although Nasseri and Eftekhari ¹¹ stated that the starry sky view was due to the presence of hyperechoic fat in a background of hypoechoic lymphatic tissue, according to their similarity to psammoma body of papillary thyroid carcinoma and microcalcifications, they might be due to calcified Hassall’s corpuscles of the thymus. ¹⁸ Hassall’s corpuscles are a distinctive feature of the thymus medulla. They are rounded epithelial structures in a lymphoid tissue background. The epithelial cells are arranged concentrically at peripheral and the central part of them, degenerated and necrosed to form cystic changes, hyalinisation, and calcification. ¹⁹

The variations of the thymic size and shapes in children and adolescents and the fact that its extension to the neck or paracardiac region might be falsely diagnosed as exophytic lesions of the thyroid, further describe the complexity and importance of proper evaluations. ¹¹ The thymus gland was symmetrical in 77.5% of our subjects. We found asymmetrical left lob prominence in 21.2%, suprasternal extension in 97.5%, adjacency to the thyroid in 53%, and to the paracardiac region in 34.4% of the subjects.

St. Amour et al. ²⁰ also reported asymmetry in the thoracic CT scan of all their subjects, noting that the left lobe was more prominent. The high frequency of symmetrical observations in our study might be due to the different modalities since the thymus is not easily distinguishable from the surrounding tissue using CT scans.

Yekeler et al. analyzed the thymus in 151 infants below 2 years. According to their report, the thymus was located symmetrically in most cases (54%), had left protrusion in 35%, and right protrusion in only 11% of the subjects. They also found Variations in the location and shape of the thymus: suprasternal extensions (45.8%), accessory thymic tissue adjacent to the superior pole (16.6%), paracardial extension (31.2%), and extension behind the brachiocephalic vein (6.2%). ²¹

In our study, the mean volume of the thymus was 21.3 ± 10.5 ml. We did not find significant differences in the thymus volume between the six age groups. There also was no significant difference in the volumes of the thymus between genders (p > 0.05). Similarly, an autopsy report on 136 sudden death victims has shown that the size of the thymus is in its maximum amount in the first few months of infancy, and it does not significantly change until puberty. Despite the observable changes in the thymus, similar to our findings, they did not find statistically significant differences in the thymus size between the age groups. ²² However, CT scan evaluations of the thymus, carried out by Moore et al., ²³ suggest that the thymus gland reaches its maximum size at puberty and does not change significantly throughout life. St. Amour et al. ²⁰ examined 71 children with no apparent sign of thymic abnormality and similarly found no statistically significant difference in anteroposterior dimension, width, or thickness of the thymus in different age groups. A 1993 ultrasound study of the thymic visual appearance and size in children aged 2–3 years, measuring the anteroposterior and longitudinal dimensions of thymic lobes, found minimal thymic size changes despite the overall body growth at these ages. ¹⁶ Even though reports have suggested that the ultrasonic measurements of the thymus may not always accurately depict the results obtained from autopsy, ¹³ this was still in accordance with other studies suggesting that the size of the thymus does not significantly change before puberty.

Overall, ectopia, asymmetry, and hyperplasia of the thymus are often associated with clinical or radiologic diagnostic problems. Fortunately, the normal thymus has several special echo-texture on ultrasound that change with age. The specificity of these appearances has made ultrasound a problem-solving modality in children. The findings of this study can aid radiologists in identifying normal observations and differentiating abnormalities in the pediatric thymus ultrasound; changes in these special echo-textures and/or abundant volume (>50 cc) are associated with abnormalities.

Certainly, this study had some limitations due to the modality’s nature. Ultrasound has some limitations in visualizing different thymic compartments partly due to the air around the thymus. This is especially true for teenagers and adults. In addition, non-geometric shapes of the thymus make measurements difficult. Moreover, probable unaccounted and confounding factors may have affected the final results. Future controlled studies with a simultaneous focus on other imaging modalities such as magnetic resonance imaging or CT as comparative studies may reveal further information on this matter.

Conclusion

The thymus is visible by ultrasound at all ages from the suprasternal view. In below 18 years, parasternal and trans-sternal views in supine or oblique positions are accessible windows. In children, thymus volume is not significantly different in age groups (about 21 ± 10 ml) The echo-texture of the thymus is hypoechoic with thin echogenic septa (liver like) in below 2–3 years of age, marked with the appearance of echogenic foci and hyperechoic echo-texture (liver like with ‘starry sky’) in 2–14 years, and uniform hyperechoic echo-texture (fatty liver like) and geographic echo-texture with coarse reticular pattern in above 14 years. The specificity of these appearances has made ultrasound a problem-solving modality in neck and mediastinal masses.