Acute Myopericarditis Induced by Subacute Thyroiditis: A Very Rare Association.

We present the case of a 38-year-old male with a history of acute chest pain associated with electrocardiographic ST-segment elevation and levels of myocardial damage markers. Few studies have evaluated chest pain and elevated troponin T during subacute thyroiditis. To the best of our knowledge, this is the reported case of myopericarditis associated with increased thyroid hormones in the bloodstream and accompanied by a significant increase in troponin T and cardiac magnetic resonance imaging findings of myopericarditis during the acute phase of subacute thyroiditis. Copyright:

INTRODUCTION

The simultaneous occurrence of thyroid disorders with heart diseases has long been recognized. Hyperthyroidism leading to tachyarrhythmias like atrial fibrillation and heart failure is well characterized.[1] We report a case of hyperthyroidism leading to myopericarditis.

The term myopericarditis denotes a primarily pericarditic syndrome with minor myocardial involvement, while the term perimyocarditis indicates a primarily myocarditic syndrome with concurrent inflammatory changes of the pericardial sac. However, the two terms are often used interchangeably without regard to the predominant type of cardiac involvement.[2]

The current diagnostic criteria of myopericarditis includes evidence of pericarditis plus elevation of cardiac inflammatory markers such as troponin or myocardial inflammatory involvement assessed by imaging modalities like cardiac magnetic resonance, but without evidence of wall motion abnormalities and reduced left ventricular (LV) function. However, in the case of wall motion abnormalities and/or reduced LV function, the term “perimyocarditis” has been proposed.[34] In general, myopericarditis is the preferred term.

We report a case of hyperthyroidism leading to perimyocarditis, which is inflammation of the myocardium predominantly with concurrent inflammatory changes of the pericardial sac. Many cases of pericarditis associated with thyrotoxicosis have been previously reported;[5678910] however, five reports have documented an association between myocarditis or perimyocarditis in conjunction with hyperthyroidism.[1112131415] We found only two case reports suggesting myocarditis in association with Hashimoto's thyroiditis Table 1 illustrates the cases the association between both acute pericarditis/myocarditis and thyrotoxicosis.[1617] Acute perimyocarditis often imitates acute coronary syndrome and evaluation of thyroid profile may be useful in young patients with no cardiac risk factors. In this case, the underlying pathophysiology may be of viral etiology or may be attributed to the effects of thyroid hormone.

Table 1

illustrates the cases that reported the association between both acute pericarditis/myocarditis and thyrotoxicosis.

Authors	Year of Publications	Type of Associations and Comments
Sugar et al.[5]	1981	Pericarditis as a complication of thyrotoxicosis
Cullen et al.[6]	2017	Pericarditis as the presenting feature of Graves’ disease
Inami et al.[7]	2014	Pericarditis in Graves’ disease and thyroid crisis
Koo EH et al.[8]	2012	Acute recurrent pericarditis accompanied by graves’ disease/first case reported.
Kortekass et al.[9]	2014	Graves’ disease as an uncommon cause of acute pericarditis
Tsai et al.[10]	2006	Acute pericarditis: A rare complication of graves’ thyrotoxicosis
Kukla et al.[11]	2008	myopericarditis complicated with cardiogenic shock mimicking ACS with ST elevation in a patient with hyperthyroidism and diabetes mellitus,
Miric et al.[12]	2018	Thyrotoxicosis as the cause of acute recurrent perimyocarditis
Gina M et al.[13]	2017	Thyroid storm and Myopericarditis due to exogenous thyroid hormone ingestion
Mavrogeni et al.[14]	2012	Hyperthyroidism combined with autoimmune myocarditis confirmed by myocardial biopsy.
Lancaster ST et al.[15]	2019	Acute autoimmune myocarditis as a manifestation of Graves’ disease
Rui Liu1 et al.[16]	2018	Sub-acute thyroiditis combined with myocardial damage
Yang and Lai17	2013	described a case of subacute thyroiditis combined with myocarditis. Patient had a rapid full recovery.

CASE PRESENTATION

A 38-year-old male, previously healthy, presented to the emergency department with severe, left-sided chest pain, stabbing in nature, radiating to the left arm associated with nausea and sweating. He denied any prior history of similar chest pain. On initial assessment, he was afebrile (oral temperature 36.8°C), with a respiratory rate of 18 breaths/min, blood pressure of 149/88 mmHg, and regular pulse of 119 beats/min. Cardiovascular examination was unremarkable, with normal heart sounds without murmurs or extra sounds. Chest examination revealed normal air entry bilaterally without rales or crepitations.

Initial electrocardiogram revealed ST segment elevation in leads II, III, AVF, V5 and V6 suggestive of inferolateral ST segment elevation acute myocardial infarction [Figure 1]. Initial troponin T was 1196 ng/L (normal 0.0–14.0 ng/L) with normal complete blood count, coagulation profile [Figure 2], renal parameters, and electrolytes. Labs revealed mildly elevated ALT of 64 U/L (0–41U/L) and AST of 59 U/L (0–40 U/L) [Table 2]. Urgent coronary angiography revealed codominant circulation with normal coronary arteries. Transthoracic echocardiogram showed normal global systolic LV function with ejection fraction of 57%, no regional wall motion abnormalities and normal valves in appearance and function. In view of normal coronaries and widespread ST elevation and PR depression on subsequent electrocardiogram (ECG) [Figure 1], along with elevated cardiac biomarkers, perimyocarditis was suspected. High-dose aspirin and colchicine were administered.

Figure 1

Electrocardiogram showing widespread ST elevation and PR depression

Figure 2

Troponin T levels during the patient's hospitalization

Table 2

Laboratory investigations during hospital admission

Laboratory values	Day 0	Day 2	Day 5	Day 9
Hemoglobin (13-17g/dl)	14.1	13.9	13.9	13.2
Creatinine (62-106 umol/l)	54	53	62	65
Sodium (136-145 mmol/L)	138	140	137	144
Total cholesterol (<5.2 mmol/L)	1.3	NA	NA	NA
Low-density lipoprotein (<3.36 mmol/L)	0.4	NA	NA	NA
Thyroid-stimulating hormone (0.3-4.2 mIU/l)	NA	0.01	0.01	<0.01 19
Tetraiodothyronine (11.6-21.9 pmol/L)	NA	>100	88.9	42.9 11.1
Free T3, tri-iodothyronine (3.7-6.4 pmol/L)	NA	32.8	26.8	12.2 3.7
Anti-thyroid peroxidase (positive >35 IU/ml)	NA	<9	NA	NA
Anti-TSH receptor antibody (positive >1.75 IU/L)	NA	<0.3	NA	NA
Anti-thyroglobulin antibody (positive >115 IU/ml)	NA	NA	813	NA
Alkaline phosphatase (40-129 U/L)	87	84	80	64
ALT (0-40U/L)	64	71	83	19.6
AST (0-40 U/L)	59	58	30	15
Hepatitis serology	Negative	NA	NA	NA
Viral PCR†	Negative	NA	NA	NA

† Viruses tested by PCR: Adenovirus, influenza, rhinovirus, coronavirus, EBV, HSV1, HSV2, RSV, enterovirus. NA i.e., the laboratory investigation was not performed or not repeated. TSH: Thyroid-stimulating hormone, AST: Aspartate transaminase, ALT: Alanine aminotransferase, PCR: Polymerase chain reaction, NA: Not applicable, RSV: Respiratory syncytial virus, EBV: Epstein-Barr Virus, HSV: Herpes Simplex Virus: HSV-1 & HSV-2

On a subsequent day, he was still found to be tachycardic with a heart rate of 115 beats/min with regular rate and rhythm, and cardiovascular examination was the same; thus, metoprolol 25 mg twice daily was initiated, despite which his tachycardia persisted. Further questioning revealed 1 month history of diarrhea, heat intolerance, and 5 kg weight loss. He denied any symptoms of preceding viral illness. Physical examination revealed no exophthalmos, lid retraction, lid lag, thyromegaly, or tremors. He had no family history of cardiac disorders or thyroid disease. In suspicion of myopericarditis secondary to hyperthyroidism, thyroid function tests were ordered, and laboratories revealed thyroid-stimulating hormone (TSH) < 0.01 mIU/L (normal 0.30–4.20 mIU/L) and free thyroxine FT4 of 100 pmol/L (11.6–21.9 pmol/L), thereby supporting our diagnosis. Carbimazole 20 mg twice daily was initiated, and the metoprolol dose was increased. Anti-thyroid peroxidase and TSH receptor antibodies were not elevated. Anti-thyroglobulin antibody was 813 IU/ml (normal 0–115 IU/ml).

Ultrasound of the thyroid gland was unremarkable with no obvious thyroid nodules. Cardiac magnetic resonance imaging (MRI) revealed myocardial edema at the basal lateral and mid inferior walls, subepicardial to mid-wall enhancement from basal to mid-anterolateral, inferolateral, and mid-inferior walls, suggestive of myocarditis. These supported our diagnosis of perimyocarditis secondary to thyroiditis. He was discharged on aspirin 600 mg/day, colchicine 0.5 mg twice/day, and metoprolol 100 mg twice/day. Carbimazole 20 mg twice daily was started at discharge. Technetium-99 methoxyisobutylisonitrile thyroid imaging 6 weeks after coronary angiography revealed very low uptake, thereby highly suggestive of thyroiditis.

Outcome and follow-up

Follow-up TFTs after 2 months revealed TSH <0.01 mIU/L, FT3 5.3 pmol/L, FT4 19.9 pmol/L. On further follow-up visits, repeated TSH was increasing [Table 3] and on the 3rd month, carbimazole was discontinued. Levothyroxine 50 mcg was started in the 4th month of follow-up, which was later increased to 75 mcg on follow-up at 6 months.

Table 3

Follow-up thyroid function tests

Lab values	1 month	2 months	3 months	4 months	6 months
TSH (0.3-4.2 mIU/l)	<0.01	<0.01	9.64	19.00	6.05
Tetraiodothyronine, FT4 (11.6-21.9 pmol/L)	12.2	5.3	3.4	3.7	4.5
Free T3, tri-iodothyronine (3.7-6.4 pmol/L)	42.9	19.9	9.3	11.1	16.4

TSH: Thyroid-stimulating hormone, FT4: Free thyroxine 4

DISCUSSION

Myocarditis is an inflammatory process of heart muscle. It can be an acute, subacute, or chronic disorder. It can be caused by a variety of infectious and noninfectious causes. It may present with focal or diffuse involvement of the myocardium by diagnostic tools. It should be suspected in any patient with or without cardiac signs and symptoms present with changes in ECG suggestive of acute myocardial injury, arrhythmia, or abnormalities of ventricular systolic function associated with a rise in cardiac biomarker levels, in particularly if these clinical findings are new and unexplained by acute coronary syndrome or other obvious cardiac diseases.

Thyroiditis is characterized by some form of thyroid inflammation. It may include conditions that cause acute illness with severe thyroid pain like subacute thyroiditis or conditions in which there is no clinically evident inflammation and the illness is manifested mainly by abnormal thyroid function or goiter like painless thyroiditis.

Subacute thyroiditis (subacute granulomatous thyroiditis) is characterized by discomfort or neck pain associated with tender diffuse goiter. In most cases, the course is very predictable of thyroid function evolution as it is a self-limiting inflammatory disease. Hyperthyroidism is typically the presentation followed by euthyroid, hypothyroidism, and ultimately restoration of normal thyroid function.

In our case, the diagnosis of subacute thyroiditis was made based on clinical symptoms, thyroid function tests, thyroid ultrasound, I131 uptake as mentioned above. While the simultaneous occurrence of myopericarditis is confirmed based on clinical history of chest pain, and significant increase in troponin T associated with ST-segment elevation in ECG. In addition, coronary angiograph should show no obstructive coronary artery disease and there are positive cardiac MRI findings of acute myopericarditis.

Many cases of pericarditis associated with thyrotoxicosis especially graves’ disease, have been previously reported [Table 1];[18] however, only five cases have documented an association between myocarditis or myopericarditis/perimyocarditis in conjunction with hyperthyroidism. There were two cases of association between were associated with myocarditis with subacute thyroiditis; also, we found only two case reports suggesting myocarditis in association with Hashimoto's thyroiditis.[1920]

To the best of our knowledge, this is the first reported case of myopericarditis associated with increased thyroid hormones in the bloodstream and accompanied by a significant increase in troponin T and cardiac MRI findings of myopericarditis during the acute phase of subacute thyroiditis. The case presentation, elevated thyroid hormones with negative anti-TSH receptor antibody does not support the diagnosis of Graves’ disease. Acute myopericarditis often imitates acute coronary syndrome, and evaluation of thyroid profile may be useful in young patients with no cardiac risk factors.

CONCLUSION

Acute perimyocarditis often imitates acute coronary syndrome and should be considered in young patients with no cardiac risk factors and normal angiography. Thyroid profile evaluation may be useful, especially in the presence of noncardiac symptoms, for example, diarrhea and weight loss, as hyperthyroidism can be associated with perimyocarditis. Early identification and treatment of underlying thyroid conditions will protect the heart from the deleterious effects of uncontrolled hyperthyroidism.

Our case adds more information to the accumulated available data about the association of a wide spectrum of cardiac disorders in patients who have different types of thyrotoxicosis. The simultaneous occurrence of pericarditis, myocarditis, myopericarditis, and thyrotoxicosis should bring more attention about the shared pathophysiology, pathology, and management. The treatment strategies are still focusing in each component rather than taking both of the disorders at the same time. Currently, there is a limited clinical data about such association, so we suggest more research to explain the reasons behind the association between cardiac and thyroid disorders.

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Conflicts of interest

There are no conflicts of interest.