Thyrotoxicosis-Induced Acute Myocardial Infarction Due to Painless Thyroiditis

Introduction

T hyrotoxicosis alters cardiovascular hemodynamics by increasing heart rate, cardiac contractility, cardiac output, and decreasing systemic vascular resistance (1). Arrhythmia and congestive heart failure are well-known cardiovascular complications of thyrotoxicosis. Thyrotoxicosis also increases the risk of angina pectoris and acute myocardial infarction (AMI) by coronary spasm. Although anginal chest pain is a common symptom in hyperthyroidism patients, AMI induced by thyrotoxicosis is unusual (2 –10).

Painless thyroiditis has been reported to account up to 23% of all thyrotoxicosis cases (11). Painless thyroiditis is caused by the destruction of thyroid follicles and release of excess thyroid hormones into circulation. Painless thyroiditis patients in the thyrotoxic phase have very similar clinical manifestations to those with Graves' disease, which can also significantly influence the cardiovascular system.

Although the causes of thyrotoxicosis are not obvious in the few cases of AMI reported in the literature, almost all reported cases are due to Graves' disease. To the best of our knowledge, this is the first case report of AMI induced by thyrotoxicosis in a patient with painless thyroiditis. The purpose of this report was to describe the case of a young man without risk factors for coronary artery disease (CAD) who presented with thyrotoxicosis-induced AMI as a result of painless thyroiditis.

Patient

A 35-year-old Korean man with chest pain for a duration of 2 hours visited the emergency room. The chest pain was characterized by a severe squeezing sensation in the anterior chest area, radiated to the left arm, and was associated with diaphoresis. Two days prior, the patient had experienced 10-minute anterior chest pain, which was self-relieved by rest. He did not show symptoms of palpitation, tremor, weight loss, heat intolerance, or recent upper respiratory infection. He did not have diabetes, hypertension, or cardiovascular disease based on medical history. The patient's family history was also unremarkable. The patient had smoked 10 pack years, but quit 5 years previously.

On arrival at the emergency room, the patient's blood pressure was 130/90 mmHg, heart rate was 88 beats per minutes, respiration rate was 20/minutes, and body temperature was 36.6°C. There was no sign of goiter, palpable thyroid nodule, exophthalmos, or tenderness of the anterior neck area. The electrocardiogram (ECG) showed 3 mm of ST-segment elevation in leads II, III, and aVF, consistent with AMI. The patient's chest X-ray was unremarkable. We diagnosed AMI based on typical chest pain and typical ECG findings. We treated the patient with aspirin, clopidogrel, sublingual nitroglycerine, and intravenous heparin infusion. Emergency coronary angiography was performed 20 minutes after his arrival at our hospital. Cardiac enzyme levels of serum creatine kinase (CK), CK-MB, and troponin-I were also elevated (Table 1). Coronary angiography showed normal coronary arteries without any suspicious stenotic lesions. The chest pain was nearly relieved after angiography. We assumed that the patient's heart attack was caused by coronary spasm and did not implement any procedures during angiography.

Initial laboratory findings revealed that the patient was in a thyrotoxic state without autoimmune thyroid disease (Table 1). A technetium-99m thyroid scan performed 10 days after his visit showed markedly reduced uptake of the thyroid gland compatible with thyroiditis.

We diagnosed the patient as AMI due to coronary spasm that was induced by thyrotoxicosis of painless thyroiditis. We treated him with diltiazem and isosorbid nitrate for 2 weeks. Thyroid function was normalized as follows at 6 weeks after his initial visit without any treatment: thyroid-stimulating hormone 2.39 mIU/L, triiodothyronine 106.60 ng/dL, and free thyroxine 1.33 ng/dL. The patients did not complain of chest pain after discharge and thyroid function remained within normal ranges on 4-, 6-, and 12-month follow-up tests. After a year, thyroid ultrasonography showed normal thyroid structure and echogenicity.

Discussion

Angina pectoris has been reported to occur in 0.5%–20% (usually 10%–12%) of patients with thyrotoxicosis (12). Burstein et al. investigated 384 cases of thyrotoxicosis, found 7 cases of typical AMI (all cases were Graves' disease including one patient who developed thyrotoxicosis after radioactive iodine [RAI] treatment), and reported that the incidence of CAD in patients with thyrotoxicosis was 3.9% (n=15) (12). We reviewed all case reports of 10 AMI patients with thyrotoxicosis that have been reported in the English literature since 1990 (Table 2). Graves' disease was diagnosed in seven patients, a multinodular goiter was diagnosed in one patient, and iatrogenic thyroxine overreplacement was diagnosed in two patients. Mean age of the patients was 48 years old and the sex ratio was female dominant (F:M=9:1). TSH levels were very low and the mean free thyroxine level was 4.89±2.28 ng/dL in all patients. At the time of initial angiography, coronary spasm was confirmed in five patients, coronary atherosclerotic obstruction was observed in only one patient, and as shown in the present study, a normal coronary angiogram was observed in four patients.

During the thyrotoxic state, myocardial ischemia may be provoked by increased left ventricular workload and reduced contractile reserve (1). Coronary vasospasm in thyrotoxicosis might result from an increased sensitivity to norepinephrine and/or a blunted response to nitric oxide–mediated vasodilatation in the coronary arteries. In the thyrotoxic state, prothrombotic substances are increased and anticoagulative factors are also significantly decreased. Serum concentration of von Willebrand factor, which is an independent risk factor for AMI, is elevated and platelet plug formation is increased in hyperthyroid patients (13). In addition, coronary vasospasm might play an important role in the development of AMI by triggering thrombus formation and slowing thrombus resolution.

Painless thyroiditis, also known as “silent” or subacute lymphocytic thyroiditis, is a clinical syndrome that manifests as transient thyrotoxicosis followed by transient hypothyroidism. Graves' disease requires an extended duration of antithyroid medication, RAI therapy, or even thyroidectomy, whereas painless thyroiditis generally resolves spontaneously and no treatment is usually warranted. This was the case in our patient. In contrast to the generally increased uptake of technetium-99m pertechnetate in Graves' disease, the uptake of RAI in painless thyroiditis is markedly decreased (14). Although the 99m-techetium pertechnetate uptake ratio (1.9%) was in the lower normal range for the current patient (reference range at our hospital: 1.7%–4.0%), overall thyroid uptake is typically decreased, which is compatible with thyroiditis. However, we could not exclude the possibility that the iodinated contrast during coronary angiography disturbed the uptake of 99m-technetium pertechnetate on the thyroid scan.

Thyrotoxicosis and the low RAI intake can be seen in thyrotoxicosis factitia, similar to our case in which a technetium-99m scan rather than an RAI uptake was performed. Serum thyroglobulin in thyrotoxicosis factitia patients has been found to be at a very low level (15). Had the patient's serum thyroglobulin level measured at admission, it would have been helpful in his differential diagnosis. Still, it is not likely for him to have thyrotoxicosis factitia with no medication history in his record. Another cause for thyrotoxicosis is toxic multinodular goiter. However, multinodular goiter usually shows unevenly distributed multiple nodular uptake and is not in accordance with the patient's case (14).

We did not use beta-blockers for controlling thyrotoxicosis symptoms in this patient, because beta-blockers can cause vasoconstriction in patients with coronary spasm due to reactive alpha-adrenergic receptor stimulation. We agreed with the opinion of Patel et al. that reasonable treatment for coronary spasm due to thyrotoxicosis includes the use of nitrates and calcium channel blockers (8). The current patient also remained free of anginal chest pain after taking these medications.

The patient did not have any CVD risk factor and the estimated 10-year Framingham cardiac risk score was <1%. We postulate that the patient had severe and/or diffuse coronary artery obstruction at about the time of his arrival to the emergency room, which spontaneously resolved or by taking nitroglycerine before coronary angiography.