key: cord-0813211-748vy4j5
authors: Thomson, Ross J; Rossberg, Nora; Davar, Joseph; Whelan, Carol
title: Myopericarditis and thyroiditis: a case report
date: 2021-07-22
journal: Eur Heart J Case Rep
DOI: 10.1093/ehjcr/ytab192
sha: 83295214b79ad9ed443f2b2163a405ebad5bb9f7
doc_id: 813211
cord_uid: 748vy4j5

BACKGROUND: Hyperthyroidism is commonly associated with adverse cardiovascular effects, including tachydysrhythmia, heart failure, and hypertension, although the association between hyperthyroidism and myopericarditis is restricted to a small number of case reports. CASE SUMMARY: A 45-year-old Caucasian male with no past medical history was admitted with chest pain. The electrocardiogram demonstrated diffuse ST-segment elevation, the troponin T rose, and he was diagnosed with myopericarditis. He was noted to have markedly deranged thyroid function tests and a diagnosis of hyperthyroidism secondary to Graves’ disease was made. He was treated with Bisoprolol, Carbimazole, Prednisolone, Ibuprofen, and Colchicine, his symptoms resolved rapidly and he was discharged. Five weeks later he re-presented with similar symptoms and recurrent pericarditis was diagnosed. His symptoms settled with a repeat course of steroids. DISCUSSION: We hypothesize that there may be an underappreciated link between hyperthyroidism and myopericarditis. Potential pathophysiological mechanisms include viral infection, autoimmunity, or changes in myocardial fat metabolism. Suggested management consists of a combination of current guidelines for the treatment of hyperthyroidism and pericardial disease, with attention to certain disease–drug interactions. Further research is required to evaluate the true incidence of hyperthyroidism-associated myopericarditis, elucidate its pathophysiology and instruct management.

Hyperthyroidism causes a variety of cardiovascular effects, including tachycardia, arrhythmias, high output cardiac failure, and hypertension. 1 However, the association between pericarditis or myocarditis and thyrotoxicosis is rare, with only a handful of case reports described. [1] [2] [3] [4] [5] [6] The cardiovascular effects of hyperthyroidism are thought to be mediated by the actions of triiodothyronine on nuclear receptors in cardiomyocytes, leading to altered expression of genes involved in intracellular calcium homeostasis and in turn to increased chronotropy and inotropy. The mechanisms by which hyperthyroidism may lead to pericarditis and myocarditis are less well characterized. We present the case of a 45-year-old male admitted with acute chest pain and diagnosed with myopericarditis and Graves' disease.

A 45-year-old Caucasian male was brought to the heart attack centre of our hospital by ambulance with a 24-h history of severe, sharp central chest pain exacerbated by inspiration and relieved by sitting forward. He had no past medical history, took no regular medications, was an ex-smoker, and exercised regularly. Physical examination was unremarkable.

A 12-lead electrocardiogram (ECG) showed diffuse concave STsegment elevation ( Figure 1 ). The patient was admitted to the coronary care unit for observation with a presumptive diagnosis of pericarditis. Treatment with Colchicine 500 lg twice daily and Ibuprofen 600 mg three times daily was commenced.

Bloods (Table 1 ) revealed a normal troponin T (11 ng/L, normal < 14 ng/L), slightly elevated NT proBNP (875 ng/L, normal < 400 ng/L), raised C-reactive protein (32 mg/L, normal < 5 mg/L), and raised white cell count (12.35 Â 10 9 /L, normal 3.5-11.0 Â 10 9 /L). Thyroid function tests showed marked hyperthyroidism: thyroid stimulating hormone <0.01 mU/L (normal 0.3-4.2 mU/L), free T4 62.2 pmol/L (normal 12-22 pmol/L), and free T3 32.8 pmol/L (normal 3.1-6.8 pmol/L). Polymerase chain reaction (PCR) for SARS-CoV-2 RNA and ELISA for SARS-CoV-2 antibody were negative. Blood cultures yielded no growth.

The endocrinology team were consulted. Antibodies against the TSH receptor were strongly positive (12.82 U/L, normal range 0-0.4 U/L) and antibodies against thyroperoxidase were negative. On specific questioning the patient denied the presence of neck pain and no tenderness was present on palpation of the thyroid. A diagnosis of Graves' disease was made. He was commenced on 5 days of Prednisolone 30 mg daily, Carbimazole 40 mg daily, and Bisoprolol 2.5 mg daily.

Over the next 2 days the troponin T rose, peaking at 181 ng/L. The diagnosis was revised to myopericarditis given the evidence of myocardial injury. The C-reactive protein also rose, peaking at 126 mg/L. A transthoracic echocardiogram showed normal biventricular function and no pericardial effusion. A cardiac magnetic resonance (CMR) imaging study ( Figure 2 and Video 1) confirmed the presence of normal biventricular function and demonstrated no evidence of myocardial oedema on STIR imaging or parametric mapping (T1 964 ms, normal range 950-1100 ms by MOLLI; T2 45 ms, normal range 45-55 ms by TruFISP) and no evidence of myocardial enhancement on late gadolinium imaging. The patient's symptoms improved rapidly, and he was discharged after 3 days to finish the 5-day course of Prednisolone and Ibuprofen, and to continue treatment with Colchicine, Carbimazole, and Bisoprolol.

The patient remained well for the next month until he once again developed severe central chest pain. He presented to the Emergency Department, where he reported compliance with medication. The ECG was relatively unremarkable (Figure 3) , with resolution of the ST-segment changes seen previously. The C-reactive protein (159 mg/L) and white cell count (13.56 Â 10 9 /L) were elevated. The free T4 had normalized (9.1 pmol/L), although the TSH remained suppressed (<0.01 mU/L). The troponin T was normal (9 ng/L). PCR for SARS-CoV-2 RNA was negative. He was admitted to the cardiology ward for evaluation.

Troponin T remained normal. The patient was diagnosed with recurrent pericarditis, without myocardial involvement. He was commenced on 5 days of Prednisolone 30 mg daily and Colchicine was increased to 500 lg three times daily. A transthoracic echocardiogram ( Figure 4 and Video 2) showed normal biventricular function, echo-bright pericardium, and a 1 cm pericardial effusion around the right ventricular free wall. The patient's symptoms improved rapidly, and he was discharged to finish the course of Prednisolone and continue treatment with Colchicine, Ibuprofen, Bisoprolol, and Carbimazole. At the latest follow-up, 3 months after his second discharge, he remained asymptomatic.

We describe the case of a previously healthy 45-year-old male who presented with a typical history of pericarditis who went on to develop concomitant myocardial inflammation and was diagnosed with Graves' disease. In this case of myopericarditis there was no preceding viral prodrome, history of drug use, or other apparent precipitant apart from thyroid disease.

The true incidence of pericarditis and myocarditis associated with hyperthyroidism is unknown, although we believe there may be an underappreciated link between the two disease entities. Mavrogeni et al. 7 assessed 50 patients with hyperthyroidism and persistent cardiac symptoms despite 1-3 months of treatment-induced euthyroidism. Using CMR, findings were compatible with myocarditis in 15 of these patients.

Several different mechanisms have been proposed to explain the link between hyperthyroidism and myopericarditis, including a viral aetiology. For example, Epstein-Barr virus has been described as a trigger for both pericarditis and Graves' disease. 2 It is plausible that our patient had an undiagnosed viral infection that initiated inflammation of the thyroid gland, pericardium, and myocardium.

There is also evidence to suggest an autoimmune aetiology of both thyroiditis and myopericarditis, in particular Graves' disease. 8 Fatourechi and Edwards 9 evaluated endomyocardial biopsy samples from 11 patients with Graves' disease and unexplained low-output cardiac failure and found that two had lymphocytic infiltrates suggestive of an autoimmune myocarditis. A further theory is that thyroid hormones may lead to a change in myocardial fat metabolism, 10 although this is more commonly described in hypothyroidism.

There is currently a lack of data to guide the management of myopericarditis specifically in the setting of hyperthyroidism. Mana gement of hyperthyroidism secondary to Graves' disease, summarized in the guidelines from the European Thyroid Association, 11 European Society of Cardiology guidelines 12 on the management of pericarditis advise restriction of physical activity, Aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), and the addition of Colchicine to improve treatment response and reduce the risk of recurrence. Low-to moderate-dose corticosteroids are suggested as second-line agents in patients who have contraindications or non-response to first-line treatments. The risk of recurrence of pericarditis is higher in patients treated with corticosteroids, especially if given in higher doses. 13 Myopericarditis is defined by the classical features of pericarditis and elevated biomarkers (e.g. high sensitivity troponin) suggestive of myocardial inflammation. Management is similar to pericarditis, except that hospitalization is recommended for monitoring and the duration of abstinence from physical activity should be at least 6 months. 12 A 2013 Cochrane systematic review 14 examining the impact of steroids on viral myocarditis found no benefit in terms of mortality benefit but a potential improvement in left ventricular function and reduction in peak biomarker level, although the trials included in this review were small and of poor methodological quality. A recent expert review advises against the use of steroids in myocarditis, except in the case of rare aetiologies such as eosinophilic or giant cell myocarditis. 15 In our patient, steroids were initiated primarily to treat thyrotoxicosis and a second course was given to treat refractory pericarditis that had recurred despite treatment with NSAIDs and Colchicine.

In the absence of specific guidance, a combination of the above treatment strategies is a sensible approach for patients presenting with hyperthyroidism-associated pericarditis or myocarditis. However, individual patient factors must be taken into consideration and management tailored accordingly. Furthermore, satisfactory treatment of the underlying hyperthyroidism seems crucial in the effective resolution of pericarditis. 8 Continuation of Colchicine to cover the period until thyroid hormones have normalized should be considered. 8 Cardiac magnetic resonance has emerged as the diagnostic modality of choice in patients with suspected myocarditis. 16 Although endomyocardial biopsy is still considered the 'gold standard' investigation, 17 this technique is not widely available and is associated with 18 set out a constellation of CMR findings that are commonly used to diagnose myocarditis, although they prioritize specificity over sensitivity, 16 and real-world studies have highlighted that patients may have biopsy-proven myocarditis despite not meeting the CMR criteria. 19 Recognizing this limitation, the authors of the Lake Louise criteria recommend that CMR is repeated within 1-2 weeks in patients with a non-diagnostic scan in whom the pre-test probability of myocarditis is high. In this case, the normal CMR may reflect technical factors such as the dose of gadolinium administered, the timing of image acquisition relative to contrast administration, and pulse sequence characteristics such as the inversion time chosen to supress the signal from the normal myocardium. 20 It may also have been a consequence of the timing of imaging relative to the onset of illness, or the nature of the myocardial damage. For example, it is conceivable that diffuse, mild myocardial damage may have led to a troponin rise but no discrete area of oedema of sufficient severity to be detected on CMR. Further research is required to elucidate the true prevalence and pathophysiology of hyperthyroidism-associated pericarditis Video 2 Video clip from a transthoracic echocardiogram, subcostal view, demonstrating a small pericardial effusion without collapse of the right atrium or ventricle in diastole.

Thyrotoxic pericarditis: an underappreciated phenomenon

Acute pericarditis: unique comorbidity of thyrotoxic crisis with Graves' disease

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Acute autoimmune myocarditis as a manifestation of Graves' disease: a case report and review of the literature

Acute pericarditis: a rare complication of Graves' thyrotoxicosis?

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The authors confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patient in line with COPE guidance.

Funding: None declared.

Ross J. Thomson studied medicine at New College, University of Oxford and is now a Specialist Registrar in Cardiology and NIHR Academic Clinical Fellow in London. His research is centred on the use of big data and real-world evidence to improve the diagnosis and management of cardiovascular disease. He sits on the finance committee of the British Cardiovascular Society and is the Lead Junior Editor at European Heart Journal -Case Reports.

Supplementary material is available at European Heart Journal -Case Reports online.Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.