Introduction

Subacute thyroiditis (SAT) is an isolated disease of viral origin, with possible pathogens including mumps virus, hepatitis B and C viruses, cytomegalovirus, enterovirus, and coxsackie viruses A and B (1). SAT is characterized by a three-phase clinical course of thyrotoxicosis, followed by euthyroidism and sometimes hypothyroidism (2). Clinically, SAT is associated with severe pain that is localized to the anterior part of the neck and may radiate up to the jaw or ears, tenderness of the thyroid gland upon palpation, and specific manifestations including fever, fatigue, asthenia, tremor, and sweating as thyrotoxicosis symptoms (3).

The Coronavirus disease of 2019 (COVID-19) pandemic was announced in Kosovo in March 2020. Multiorgan effects of the virus were shown on diabetes very early, while its consequences in other endocrine glands remained unclear until recently. However, shortly after May 2020, the first case of SAT after a COVID-19 record was reported, prompting further observation of its spread.

We investigated the clinical and laboratory characteristics and follow-up data of patients with SAT in COVID-19 patients in Kosovo.

Case Presentation

This patient series included 7 individuals diagnosed and treated with SAT. All patients were admitted to the Outpatient Clinic of Endocrinology of the University Clinical Center of Kosovo or the Endoclinic Policlinic between May 2020 and May 2021. Demographic, clinical, biochemical, and imaging records were available in the medical health records. We informed the patients about this case series presentation and obtained their informed consent.

Of the seven cases, six were women and the age range was 17 to 65 years. All but one were young and did not have comorbidities. One patient had undergone thyroid lobectomy a few years previously. Six individuals presented with neck pain, and one patient showed atypical symptoms such as fear and no neck pain. Headache, odynophagia, fatigue, laziness, fever, and signs of thyrotoxicosis (e.g., tachycardia, anxiety, and insomnia) were common. The time between the onset of SAT symptoms and diagnosis was 5 to 30 days after COVID-19. Six patients had confirmed past real-time quantitative-polymerase chain reaction positive COVID-19, whereas one patient was diagnosed through serological tests (IgM and IgG).

Biochemical tests showed increased levels of C-reactive protein (CRP), erythrocyte sedimentation rate, total and free fractions of thyroxine (FT4) and triiodothyronine (FT3), and reduced thyroid-stimulating hormone (TSH). The gland was soft but painful on palpation, as confirmed by ultrasound examination. Typical ultrasonography findings of SAT were identified, including heterogeneous parenchyma and central hypoechoic areas (Figure 1) and reduction of radioiodine uptake in SAT scintigraphy (Figure 2).

Almost all patients were treated with corticosteroids or non-steroidal anti-inflammatory drugs, leading to complete improvement of inflammatory parameters and normalization of thyroid hormones (Table 1). Vitamin D supplementation at a dosage of 2000-5000 IU/day was prescribed for most patients.

Discussion

In this study, we found that almost all patients with SAT after COVID-19 had a typical clinical presentation and responded well to corticosteroid treatment. Because large clinical studies with patients with SAT after COVID-19 have not been published, case reports or series and systematic reviews dominate the literature. The most plausible theory explaining direct cellular damage in thyroid tissues due to COVID-19 is that the Severe acute respiratory syndrome-Coronavirus-2 virus identifies angiotensin-converting enzyme-2 and TMPRSS2 mRNA receptors as cellular entrance receptors, and these receptors are expressed in follicular thyroid cells (4-6). Direct follicular cell damage can spread thyroid hormones into the plasma, explaining the thyrotoxic clinical features (e.g., tachycardia, anxiety, insomnia).

In terms of clinical, imaging, and laboratory features, SAT after COVID-19 is unlikely to differ from SAT of other viral origins (mumps, rubella, influenza, coxsackie, adenovirus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, hepatitis E, and HIV) (7). SAT after COVID-19 also presents with classical clinical features of neck pain, anxiety, and thyrotoxicosis (high FT3 and FT4 and suppressed TSH) and typical ultrasound findings (8), as well as high inflammatory markers such as CRP, as shown in our cases.

Similar to other etiologies, the treatment of SAT after COVID-19 includes short-term corticosteroids, beta-adrenergic receptor blockers, and analgesics (9). On the other hand, in most cases, corticosteroids with a lower average dose of 25-30 mg/day have been used compared with SAT of other viral origins. Increased predisposition to systemic infections, impaired immune responses, or even the development of autoimmune diseases due to vitamin D insufficiency have been reported (10). Nevertheless, more studies on the benefits and prognostic role of vitamin D supplements in COVID-19 are warranted (11).

Our series included more women than men; no patient required hospitalization or developed hypothyroidism, and all patients showed mild COVID-19. Similar results were reported in a study that compared patients with mild or severe COVID-19 pneumonia. None of the hospitalized patients with mild pneumonia had hypothyroidism, whereas 3.2% of those with severe pneumonia did have hypothyroidism (12).

The presentation of such cases is crucial for physicians of different specialties to identify potential complications of COVID-19, especially rare cases such as SAT that may be overlooked during routine clinical practice. Recognition of this clinical entity is important because timely treatment can lead to a complete return to normal thyroid function. However, it is essential to investigate the possibility of hypothyroidism at a later stage. Adequate follow-up after recovery from COVID-19 is necessary because SAT, except in the early phase, may be found even several months after the initial infection.

Conclusion

Our findings contribute to the growing body of evidence on the impact of COVID-19 on the endocrine system and can help physicians identify and manage potential complications such as SAT.

Ethics

Informed Consent: We informed the patients about this case series presentation and obtained their informed consent.

Authorship Contributions

Surgical and Medical Practices - Concept - Design - Data Collection or Processing - Analysis or Interpretation - Literature Search - Writing: M.E.S., I.S., M.R.P.

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

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