Post COVID-19 Thyroiditis Documented On Tc-99m Pertechnetate Thyroid Scan: A Case Series and Review of Literature

INTRODUCTION

Subacute thyroiditis (SAT) is a self-limited inflammatory thyroid disease. It is also known as De Quervain's thyroiditis or viral thyroiditis. It usually follows or coexists with an upper respiratory tract infection. The incidence of SAT is 12.1 cases per 100,000/year, and it is more frequent in young women.^[1] It is characterised by neck pain, general symptoms, and thyroid dysfunction.

The aetiology of SAT is presumed to be usually viral. It is commonly associated with enterovirus, coxsackievirus, mumps, measles, and adenovirus.^[2] With the ongoing pandemic of the SARS-CoV-2 virus and the identification of its endocrinological effects, SARS-CoV-2 should be included in the list of viral triggering factors of SAT. Moreover, as the pandemic is still progressing, SARS-CoV-2 should be considered an important triggering factor for SAT.^[3] The interlinkage between thyroid hormones, the immune system, and the direct cytotoxic effect of the virus is proposed to play a role in SAT.^[4] Here, we report 3 cases of post-COVID-19 thyroiditis, documented on a Tc-99m pertechnetate thyroid scan.

CASE SERIES

Case 1

31year old male had IgA nephropathy for ten years (since 2012). He progressed to end-stage renal disease and has been on maintenance haemodialysis since 2020. He had a history of COVID-19 infection. The infection was mild and recovered with conservative management. Two months later, he developed generalised weakness and palpitations. Thyroid function tests revealed raised T3 and T4 hormone levels [3.26 nmol/L (1.3-3.1) and 176 nmol/L (58-162), respectively] along with suppressed TSH <0.014 mI U/L (0.4-4.0). Upon examination, no neck swelling, pain, or tenderness was present. Except for palpitations, no other signs or symptoms of hyperthyroidism were noted. The patient has been on antihypertensives (calcium channel blockers) and calcium supplements for the past ten years. He was referred for a Tc-99m pertechnetate thyroid scan. It showed reduced pertechnetate uptake in both lobes of the thyroid, consistent with thyroiditis [Fig 1]. The patient was given beta-blockers. He became euthyroid after one month.

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Fig 1:

31-year-old male patient who presented with generalized weakness and palpitations with suppressed TSH, two months post-COVID 19. Thyroid scan showed reduced pertechnetate uptake in both lobes of the thyroid, consistent with thyroiditis (blue arrow).

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Case 2

A 51-year-old, post-menopausal female with no comorbidities presented with high-grade fever, generalised weakness, and cough. COVID-19 was diagnosed on RTPCR. Her inflammatory markers and chest X-Rays were unremarkable. She was managed with conservative management. Ten weeks later, she presented with complaints of pain and tenderness in the neck. There was no neck swelling or other symptoms of hyperthyroidism. Thyroid function tests showed hyperthyroidism. It showed raised T3 hormone levels [1.83 ng/ml (0.6-1.81)] with suppressed TSH <0.01 uIU/ml (0.35-5.5). T4 levels were within normal limits [11.7 ug/dl (5.01-12.45)]. Tc-99m pertechnetate thyroid scan revealed absent uptake in the neck region, suggestive of thyroiditis [Fig 2a] Ultrasound of the neck region showed features suggestive of thyroiditis [Fig 2b and 2c]. She received supportive management and became euthyroid after two months.

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Fig 2:

(a) A 51-year-old woman presented with complaints of pain and tenderness in the neck ten weeks after recovering from SarsCov2. Tc-99m pertechnetate thyroid scan revealed absent uptake in the neck region (arrow). (b) Ultrasound of the neck suggests a mildly enlarged thyroid with increased vascularity and (c) increased echogenicity.

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Case 3

28 years old female had a COVID-19 infection. It was mild, and no hospitalisation was required. She presented with neck pain and swelling two months later. She also had generalised weakness, restlessness, and palpitations. A neck examination revealed goiter grade II. Her T3 and T4 hormone levels were 3.30 ng/ml (0.6-1.81) and T4 21.93 ug/dl (5.01-12.45), respectively, with suppressed serum TSH [0.03 mIU/ml (0.35-5.5)]. She was prescribed antithyroid and beta-blocker drugs for the same earlier. Tc-99m pertechnetate thyroid scan showed absent pertechnetate uptake in the neck region, suggesting thyroiditis [Fig 3]. The symptoms subsided over the next three months after being diagnosed with thyroiditis and receiving supportive therapy.

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Fig 3:

28 years old female presented with neck pain and swelling; thyroid scan suggested thyroiditis (arrow). The symptoms subsided over the next three months after receiving supportive therapy.

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DISCUSSION

SAT more commonly affects females than males, with a ratio of 4:1. Although self-limited, it can manifest both during the active viral infection and within two to twelve weeks of a recent viral infection.^[5] A typical viral prodrome of myalgias, malaise, and fatigue is seen in most patients. SAT typically presents anterior neck pain that radiates up to the jaw or ear on either side, with or without a tender diffuse goitre. Low-grade fever, fatigue, pharyngitis, myalgia, and mild hyperthyroid symptoms may be noted. In a usual clinical course, within three months, half of the patients experience transient symptoms of thyrotoxicosis followed by euthyroidism or, less commonly, hypothyroidism. However, the clinical characteristics of the disease have been changing significantly in recent years. Painless SAT with less fever is being reported. Signs and symptoms of thyrotoxicosis are noted in a minority of SAT patients. Tachycardia, a deterioration of tachycardia, or an occurrence of new heart arrhythmias have been documented as typical SAT symptoms in COVID-19 patients.^[3]

The affinity of SARS-CoV-2 to the thyroid gland is presumed via ACE2 receptors, which are more frequent in the thyroid than in the lung. Angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) act as receptors for the virus. SARS-CoV-2 enters the lung, deposits in the lung parenchyma, and then enters the host cells. Endocrine glands such as the pancreas, hypothalamus, pituitary, thyroid, adrenal glands, testes, and ovaries express ACE2 and TMPRSS2. The highest concentration is noted in the testes, followed by the thyroid, and the lowest in the hypothalamus.^[6] Thyroid follicles are infiltrated, resulting in a disrupted basement membrane and rupture of the follicles. This injury results from cytolytic T-cell recognition of viral and cell antigens. Other thyroiditis-associated viral infections have been associated with virus-like particles in the thyroid tissue.^[2] Direct viral replication is not isolated in the thyroid but is noted in the infiltrating inflammatory cells.^[7] Therefore, it is unclear whether follicle damage in SAT is caused by direct viral infection of the gland or by the immunological response to the infection.^[8] Immune mechanisms, such as the cytokine storm, result in apoptosis and local damage. Another potential mechanism is attributed to central hypothalamus-pituitary dysfunction, which is reinforced by the findings of central hypothyroidism and central hypocortisolism in SARS patients.^[9]

Autoimmune aetiology of SAT is also proposed, highlighted by a female preponderance, which is well documented in the literature.^[10] The study has implicated COVID-19 in developing various autoimmune diseases, such as SAT, Kawasaki disease, antiphospholipid syndrome, immune thrombocytopenic purpura, autoimmune haemolytic anaemia, and GuillainBarré syndrome. This also highlights the association between autoimmune diseases and infections.^[11] The effect of COVID-19 on aggravation of existing endocrine diseases or adverse prognoses in patients with prior endocrine history, like obesity and diabetes mellitus, is under investigation.^[12] A retrospective study investigated thyroid function in 287 non-critical patients hospitalised for COVID-19, 20.2% had thyrotoxicosis, and 5.2% presented with hypothyroidism. Thyrotoxicosis also corresponded to interleukin 6 levels in these patients.^[13]

Out of the reported post-COVID 19 SAT, a female preponderance is noted. The age of the patients ranged from 18 to 68 years, time from COVID-19 diagnosis to typical thyroiditis symptoms ranged from 5 to 42 days.^[6] Hallmark lab findings include elevated ESR (> 50 mm/hr) and CRP, low TSH with raised free T4 and T3 during the early stages of the illness, a normal or mildly elevated leukocyte count, and mild anaemia. There is a low thyroglobulin concentration, with an absent or low titer of circulating thyroperoxidase and thyroglobulin antibodies.^[9] Antithyroid antibodies appear unhelpful and have not been recommended routinely.

Ultrasonography shows a normal or enlarged thyroid, with diffuse mild hypoechoic or focal markedly hypoechoic areas, and the colour Doppler sonography demonstrates low flow. ^[12] Tc-99m pertechnetate thyroid scan shows a low or faint heterogeneous uptake during the hyperthyroid phase, consistent with SAT. Scintigraphy is particularly useful over the ultrasound and biochemical markers in dubious cases.^[14]

Anti-inflammatory therapy with NSAIDs or prednisolone is usually the mainstay of treatment. Hyperthyroidism symptoms such as palpitations, anxiety, or tremors benefit from treatment with a beta-blocker such as propranolol. It is important to balance the risk of recurrence during glucocorticoid dose tapering and complications of long-term glucocorticoid therapy. In a randomised controlled study by Duan et al., Short-term prednisone was found to have a better safety profile for ameliorating moderate-to-severe symptoms of subacute thyroiditis.^[15] The antithyroid medication has not proven effective during the thyrotoxic stage of illness, although it may be used as an adjuvant.

Subacute thyroiditis should also be considered in patients who receive the COVID-19 vaccine and subsequently develop symptoms or signs of hyperthyroidism. The mechanism of SAT induction may be applied to vaccines.^[16]

Our patients had the clinical manifestations and laboratory findings of thyrotoxicosis, with a thyroid scan supporting the diagnosis of SAT. The time frame of appearance and evolution of symptoms fits with the disease course of SAT. Documented COVID-19 diagnosis was available in all, and other triggers of subacute thyroiditis were ruled out. The diagnosis of SAT on thyroid scan and response to conservative management strengthen SAT post-COVID-19 infection. To date, only a few case reports of post-COVID thyroiditis have been reported.^[5,9,17-19], out of which only one has been documented on an iodine-131 thyroid scan.^[20]

CONCLUSION

The diagnosis of SAT can be challenging in some instances. Its timely identification may be difficult due to the absence of classic symptoms and crossover of typical clinical features between COVID-19 and thyrotoxicosis. SAT is one of the aspects of the covert long COVID syndrome. This case series illustrates the same. The emerging data suggest that COVID-19 may be another virus that merits the list of viral culprits in SAT. Clinical features consistent with SAT and a history of recent COVID disease should prompt investigation of a thyroid scan for definitive diagnosis.