Ultrasound signs of large segmental thyroid regeneration in Hashimoto’s thyroiditis: a case report of two cases

Introduction

Physiological and reparative types of regeneration are characteristic of thyroid tissue (1). The cellular composition of the thyroid is almost completely renewed in healthy people in almost 5–8.5 years (2,3). Under certain additional conditions, the regeneration rate can be significantly higher. For example, thyroid regeneration is more active at a young age, after surgical removal of part of the lobe, under the influence of certain substances, etc. (1,4). Of course, there are factors that inhibit regeneration (5).

For more than a century, microscopy has played a leading role in the diagnosis of thyroid regeneration. Other methods for studying regeneration complement the capabilities of the microscope to varying degrees. Ultrasound, unfortunately, is not used to assess reparative processes in the thyroid. This situation, on the one hand, is associated with the dominant use of ultrasound for thyroid nodules. On the other hand, the reason for inattention to the capabilities of ultrasound may be the predominance of hormonal and immune blood tests in the diagnosis. As a result, interest in thyroid regeneration has shifted to the search for transplantation opportunities (6).

However, in vivo animal studies (mice) under conditions typical of Hashimoto’s thyroiditis have revealed relatively rapid development of new follicles and the formation of young tissue (7). Stem cells became the sources of such reparative regeneration. This process of thyroid regeneration has also been studied mainly microscopically.

Ultrasound search for signs of regeneration in the thyroid turned out to be biased towards the nodular process. For the first time, an ultrasound sign of benign regeneration in Hashimoto’s thyroiditis was presented by Bonavita et al. in the form of a small isoechoic nodule with the author’s name “white knight” (8) (Figure 1A). This phenomenon in the gland has all the signs of a nodule.

Figure 1 Ultrasound images of examples of nodular and small (lobular) segmental regeneration. (A) An isoechoic reparative nodule measuring 9.8 mm × 7.2 mm × 11.1 mm (“white knight”; yellow arrow) is visible in the cranial part of the thyroid lobe. Two lobules are also visible (white arrows). The patient is 67 years old, mild hypothyroidism, significant excess of antibodies to thyroid peroxidase and thyroglobulin. (B) In the lobe, small and large isoechoic lobules (arrows) are visible among the hypoechoic tissue. The patient is 45 years old, significant hypothyroidism, significant excess of antibodies to thyroid peroxidase and thyroglobulin. (C,D) Lobe and its enlarged fragment. In the ventral part of the lobe, among significant hypoechoic tissue (probably lymphoid), an isoechoic lobule of a spherical shape 1.4 mm × 1.2 mm is noticeable (arrow). On the left, an isoechoic area is outlined with a wide white outline, which can be perceived as regeneration in a large segment. On the right, a thin outline shows an area with signs of average segmental regeneration. The patient is 19 years old, euthyroid, normal levels of antibodies to thyroid peroxidase and thyroglobulin.

Typically, in addition to such a reparative nodule (“white knight”), ultrasound often shows several new (isoechoic) lobules in the lobes (Figure 1A). The size and characteristics of such lobules do not allow them to be classified as nodules (Figure 1).

A full literature review on the topics “ultrasound of thyroid regeneration”, “ultrasound of diffuse thyroid regeneration”, “regeneration of thyroid segments” and a related author has not been carried out. But a search of publications on these topics in PubMed and examination of guidelines on thyroid ultrasound suggest a lack of reports on this topic in the scientific literature (9,10).

For the first time, we present two cases of Hashimoto’s thyroiditis with ultrasound evidence of large segmental thyroid regeneration. This article is presented in accordance with the CARE reporting checklist (available at https://aot.amegroups.com/article/view/10.21037/aot-24-17/rc).

Case presentation

Both female patients with similar ultrasound signs came to our clinic within 20 days of each other. Both are the same age, but with different histories of primary hypothyroidism and Hashimoto’s thyroiditis. The most important data from these two cases are listed in Table 1.

Medical history of the patient 1

In 2018, during examination before pregnancy and after childbirth, normal thyroid hormonal metabolism was revealed. In November 2022, a blood test showed signs of minor hypothyroidism and a moderate autoimmune process: thyroid-stimulating hormone (TSH) 5.9 mU/mL (3.5–4.9), free thyroxine (FT4) 9.5 pmol/L (9.0–19.0) and thyroid peroxidase (TPOAb) 629 IU/mL (0–5).

The patient reports a normal lifestyle. However, since 2019 she has been under constant mental stress due to family reasons that are still ongoing. She suffered maximum mental stress in 2021. A control blood test in 2023 revealed signs of significant hypothyroidism and autoimmune thyroiditis (Table 1). After which she contacted our clinic.

Thyroid ultrasound revealed signs of widespread significant stromal swelling (11), about 90–95% of hormone-producing tissue, small signs of lobular destruction and a large isoechoic segment in the left lobe (Figure 2A,2B). Doppler mode revealed a significant intensity of blood flow in both lobes, as well as a separate increased blood flow of an isoechoic area in the left lobe (Figure 2C,2D), to which dilated great vessels approached.

Figure 2 Ultrasound images of the thyroid of the first patient. (A,B) Longitudinal and transverse views of the left lobe. Among the significant hypoechogenicity, an isoechoic area of tissue is visible. (C,D) In the power Doppler mode with optimal PRF, significantly intense blood flow is visible in the isoechoic area and the approach of the great vessels to it. PRF, pulse repetition frequency.

Medical history of the patient 2

After the fourth birth in 2018, a blood test showed TSH 20 mU/mL (0.27–4.20). On the doctor’s recommendation, she began taking levothyroxine 50 mcg daily. In the fall of 2019, due to an excess of TSH, the dose of the drug was increased to 75 mcg, and in 2022 to 82.5 mcg/day. Since May 2023, she has been regularly taking 100 mcg of Levothyroxine. The patient has been living in a cold region in recent years, despite the fact that she was born and lived most of her life in a country with a warm climate.

Ultrasound showed significantly hypoechoic thyroid tissue [a sign of stromal swelling (11)], among which large isoechoic areas were present in two lobes (Figure 3A-3D). These areas were similar, located in the same parts of the lobes and did not have a uniform border line. Power Doppler mode revealed a slight increase in blood flow intensity in two lobes, including in isoechoic areas. With increased sensitivity [decreased pulse repetition frequency (PRF)] in color Doppler mode, more pronounced blood flow in the isoechoic area became visible (Figure 3E,3F).

Figure 3 Ultrasound images of the thyroid of the second patient. (A-D) Longitudinal and transverse views of both lobes. Among the significant hypoechogenicity in the caudal part, an isoechoic area of tissue is visible. (E,F) Color Doppler mode at a more sensitive setting (at low PRF). There is more intense blood flow in the isoechoic area of the right lobe and the great vessels approaching it. PRF, pulse repetition frequency.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

It is known that regeneration in Hashimoto’s thyroiditis is noticeable on ultrasound with isoechoic nodules (8). It is also known that the structure of benign nodules is identical to the extranodular tissue of the gland (12). Consequently, nodular regeneration should in principle be similar to diffuse (non-nodular) thyroid regeneration.

Our knowledge and experience show that this type of regeneration is usually accompanied by the regeneration of individual lobules in the parenchyma of the gland. They are visible as isoechoic, sphere-shaped areas measuring 1–2 mm (Figure 1). Such lobules do not belong to nodules, but to a diffuse process. After all, the largest size of the lobule is usually 1.0–1.7 mm. However, ultrasound signs of diffuse thyroid regeneration turned out to be beyond the attention of specialists.

Ultrasound shows that diffuse changes can occur widely and in thyroid segments (11). These processes can be not only destructive, but also regenerative. Local regeneration in Hashimoto’s thyroiditis has been confirmed experimentally (7). Regeneration can occur not only in the small segment (lobule), but also in the medium and large segments.

These two cases show a variant of regenerative processes in large segments of the thyroid. In the lobe, among significantly hypoechoic tissue, a large isoechoic area is visible without specific signs of a nodule (without a clear uniform border, etc.). The second patient has the same reparative signs, but in two lobes. This is new tissue, so it appears isoechoic. Rare hyperechoic punctate elements in these segments can be assessed as phenomena of compensatory fibrosis. After all, connective tissue performs a trophic function, promoting the formation of follicles and the penetration of blood vessels and nerves (7,13). This condition confirms more active blood flow in isoechoic segments in both patients. The approach to isoechoic areas of the great vessels is also determined (Figures 2,3). Consequently, we observe ultrasound signs for two main flows of information to the regeneration zone—nervous and fluid.

Two natural processes always occur in the thyroid parenchyma—destruction and regeneration. Very light gray (isoechoic) tissue in the thyroid on ultrasound is an absolute sign of relatively recent regeneration. This is young tissue. It is precisely this process, isolated in large segments, that is shown by ultrasound in two patients. The remaining tissue (significantly hypoechoic) has stromal swelling. This phenomenon is not associated with thyroiditis and shows a separate neural influence (11).

Cases of isolated large-segmental regeneration among significantly hypoechoic parenchyma are rare in the practice of our clinic. However, signs of such regeneration in several segments of the lobe are observed more often. But these processes are almost invisible compared to the ultrasound picture in the two patients presented (Figure 1C,1D).

One might think that nodular and diffuse variants of thyroid regeneration are compensatory processes. However, regeneration alone does not lead to the restoration of hormonal metabolism if the causes and basis of the disease are not eliminated. Our two cases confirm this. In each patient, with a sufficient amount of hormone-producing tissue in the thyroid, we see significant hypothyroidism with a deficiency of thyroid hormones (Table 1). After all, primary hypothyroidism (as stimulation of the thyroid with TSH) in most cases is not associated with depletion of gland tissue, but with increased consumption of thyroid hormones by the organism (14).

Further evidence of the latent thyroid hormone-producing potential can be seen in rare cases of conversion from primary hypothyroidism to Graves’ disease (14,15). We observed such a course in some of our other patients. Our experience and data from other specialists suggest that regeneration and its ultrasound signs do not have a significant role in the state of thyroid hormonal metabolism against the background of the underlying disease.

The leading mechanisms of thyroid regeneration remain unknown (1,6,16). Only some features of this process have been revealed. However, when diagnosing thyroid conditions, all modern options, including ultrasound, should be used. Ultrasound demonstrates the macro level of processes in the gland, at which important signs of regeneration are visible.

Identification of isoechoic tissue in the thyroid segments is an absolutely sufficient sign to confirm regeneration. The use of puncture biopsy with cytological examination is not required. In addition, puncture biopsy is not indicated for benign processes.

Determining ultrasound signs of diffuse thyroid regeneration does not yet allow us to understand their place in the choice of treatment tactics and prognosis. However, the new knowledge will help researchers further study diffuse thyropathies.

Conclusions

Regeneration in the thyroid can occur in the form of a large segment. This is a variant of diffuse regeneration. Ultrasound shows a large isoechoic area extending along the lobe, without a clear uniform border line and in some cases located among hypoechoic tissue. Single pinpoint hyperechoic elements may be visible in this isoechoic area. The intensity of blood flow in this segment is usually increased. The success of segmental regenerative processes of the thyroid is not a sufficient condition for the normalization of hormonal metabolism.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The author has completed the CARE reporting checklist. Available at https://aot.amegroups.com/article/view/10.21037/aot-24-17/rc

Peer Review File: Available at https://aot.amegroups.com/article/view/10.21037/aot-24-17/prf

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://aot.amegroups.com/article/view/10.21037/aot-24-17/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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