Coronary Artery Bypass Grafting in the Presence of Severe Hyperthyroidism: A Case Report

Introduction

Subclinical hyperthyroidism, characterized by low thyroid-stimulating hormone (TSH) and normal free tetraiodothyronine (FT4) levels, has an annual incidence rate of approximately 200 cases per 100 000 person-years, and some cases progress to overt hyperthyroidism [1].

Basedow disease is an autoimmune hyperthyroidism in which the production and secretion of thyroid hormones are increased because of the expression of stimulating autoantibodies, including TSH receptor antibody (TRAb) or thyroid-stimulating antibody (TSAb). Diagnosis relies on clinical findings, such as signs of thyrotoxicosis, diffuse thyroid enlargement, and protruding eyeballs or other characteristic eye symptoms, as well as laboratory results, including elevated FT4 and/or free triiodothyronine (FT3), low TSH, positivity for TSH receptor antibody or thyroid-stimulating antibody, and elevated or normal radioactive iodine or technetium uptake on thyroid scintigraphy demonstrating diffuse thyroid enlargement. Diagnosis is confirmed when 1 or more clinical findings are present along with all 4 laboratory findings. Furthermore, treatment for Basedow disease includes antithyroid medication, surgery, or isotope therapy, and post-treatment follow-up involves monitoring FT4, TSH, and TRAb levels.

Hyperthyroidism is rarely associated with severe clinical manifestations of thyrotoxicosis [2]. The incidence of thyroid storm is 0.20 to 0.76 per 100 000 population annually; among hospitalized patients, the incidence rises to 4.8 to 5.6 per 100 000 annually [3,4]. Furthermore, the incidence rate increased to 1.03 by 2020, with a corresponding rise in mortality to 5.3% [5]. However, only 2 cases of thyroid storm after coronary artery bypass grafting (CABG) have been reported; these cases were associated with poor prognoses involving complications [6,7]. This report describes the case of incidental hyperthyroidism in a 58-year-old man undergoing preoperative evaluation for CABG surgery in triple-vessel coronary artery disease.

Case Report

A 58-year-old man was diagnosed with hypertension and diabetes at the age of 48 years and had been receiving medication for these conditions since he was 50 years old. He presented with primary symptoms of anterior chest pain and shortness of breath during exertion, specifically during golfing. Additionally, he experienced postprandial chest pain accompanied by vomiting. Following admission, the patient had further episodes of chest pain and was placed on a continuous infusion of coronary vasodilator medication, which required him to remain on bed rest.

The patient had undergone surgery for sinusitis 6 months earlier. He had not been vaccinated against influenza or COVID-19 because of an allergic reaction to the vaccination. His family history included a father who had died suddenly from cardiac disease; however, details were not available. He had a history of heavy alcohol consumption and smoked 20 cigarettes per day. He was receiving medical treatment for hypertension (amlodipine besylate 5 mg/day, diltiazem hydrochloride 100 mg/day), diabetes (teneligliptin hydrobromide hydrate 20 mg and canagliflozin hydrate 100 mg/day), dyslipidemia (fenofibrate 80 mg/day), and hyperuricemia (allopurinol 100 mg/day). His blood pressure was 124/70 mmHg, heart rate 88 beats per min, height 169 cm, and weight 60 kg. No heart murmur, neck masses, or enlarged thyroid glands were detected.

Electrocardiography revealed a normal sinus rhythm (Figure 1A). Chest radiography revealed a cardiothoracic ratio of 42% (Figure 1B). Echocardiography after admission revealed a left ventricular ejection fraction of 65%. Three-dimensional computed tomography (CT) revealed severe coronary 3-vessel disease (Figure 2A–2C); therefore, urgent coronary angiography was performed. Cine angiography showed 100% occlusion in the right coronary artery (Figure 3), 95% stenosis in the right atrioventricular node branch, 90% stenosis in the proximal left anterior descending artery and diagonal branch, and 95% stenosis in the proximal left circumflex artery (Figure 3A–3C). Therefore, we planned an urgent CABG. However, marked hyperthyroidism was detected. The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score II revealed 24.2% in percutaneous coronary intervention and 18.5% in CABG.

Biochemical tests revealed elevated N-terminal pro-brain natriuretic peptide and hemoglobin A1c levels. In addition, preoperative testing before CABG revealed abnormal thyroid function and positivity for thyroid autoantibodies (Table 1). The thyroid gland was diffusely enlarged and echogenically heterogeneous (Figure 4A). In addition, the internal blood flow (Figure 4B) and blood flow in the superior thyroid artery (Figure 4C, 4D) was increased. We diagnosed Basedow disease based on clinical findings (tachycardia, weight loss, increased sweating indicative of thyrotoxicosis, and diffuse thyroid enlargement) and laboratory findings (including elevated free T4 and free T3 levels, low TSH, and TRAb positivity). A thyroid biopsy was not performed, because discontinuing anticoagulant and antiplatelet therapy was considered unsafe owing to the unstable angina status of the patient.

Medical treatment (thiamazole 80 mg/day; potassium iodide 50 mg/day) was initiated for hyperthyroidism. Shortly thereafter, the patient developed transient tachycardia attacks and a fever of 37.0 to 38.5°C. The Burch Wartofsky Point Scale (BWPS) score [8] was 40 points (rising to 50 points when transient atrial fibrillation was added). Although no definitive signs of thyroid storm were observed after admission, the 50-point BWPS score of the patient based on clinical course was considered extremely critical. CABG was postponed owing to concerns about a postoperative thyroid storm.

Two weeks after initiating treatment for hyperthyroidism, the patient developed leukopenia as a adverse effect of thiamazole, with a reduced white blood cell count of 2800×109/L. Consequently, thiamazole and potassium iodide were discontinued. On the same day, the patient developed a fever of 38.5°C. Blood cultures were negative for bacteria, but pharyngeal cultures showed high levels of Staphylococcus aureus; therefore, he was diagnosed with bacterial pharyngitis. He received 5 days of intravenous antibiotic therapy (ampicillin sodium/sulbactam sodium 6 g/day), which resolved the infection quickly. However, an urgent decision regarding further management of his thyroid condition was necessary. His internist suggested a thyroidectomy, and we requested a thyroidectomy from the otolaryngology department. However, owing to the presence of severe triple-vessel coronary artery disease, thyroidectomy was deemed inappropriate. Generally, surgery is contraindicated in cases of uncontrolled thyroid function, while recovery following radiation therapy can take several months or longer. Considering the severe and complex coronary artery disease of the patient, thyroidectomy was considered too invasive. However, at the request of the patient, and given his frequent episodes of chest pain, which were easily triggered, we reluctantly proceeded with CABG first.

We meticulously performed an off-pump CABG. The left internal thoracic artery was anastomosed to the first diagonal branch artery and the left anterior descending artery, and the right gastroepiploic artery was grafted to the posterior descending artery, atrioventricular node, and posterolateral branch arteries. The operative time was 245 minutes. Using a comprehensive approach, we successfully managed sinus tachycardia during anesthesia induction. The anesthesiologist initiated a regimen of landiolol hydrochloride at 8 μg/kg/min, gradually increasing the dose to a maximum of 35 μg/kg/min during surgery and reducing it to 20 μg/kg/min by the end of surgery. The pulse rate was maintained at a controlled 80 to 100 beats/min throughout the experiment. Blood pressure was maintained between 90 and 120 mmHg using only a minimal dose of noradrenaline (0.05 μg/kg/min).

Methylprednisolone (1000 mg) was administered intraoperatively and continued until the first postoperative day (250 mg) to prevent thyroid storm. We performed continuous hemodiafiltration (CHDF) with slow plasma exchange for 20 hours from the start of surgery until the following morning. A total of 960 mL of fresh frozen plasma was transfused intraoperatively and 960 mL postoperatively, with equivalent volumes removed using CHDF. The patient was also treated with intravenous gamma globulin (IVIG) for 3 days before surgery and 3 days after surgery. He experienced no hemodynamic compromise during this period, and his thyroid function slowly declined. On the following day, landiolol hydrochloride was discontinued, and oral diltiazem (90 mg/day) and bisoprolol fumarate (1.25 mg/day) were initiated. Potassium iodide (100 mg/day) was also administered for hyperthyroidism. His intensive care unit stay lasted 20 hours.

FT3 normalized on postoperative day 3, and FT4 normalized on postoperative day 7; however, TRAb remained elevated 6 months after surgery (Figure 4). Postoperatively, hemodynamics were stable, but the fever persisted. His C-reactive protein level was 24.42 mg/dL, white blood cell count increased from 7.7 to 11.9×109/L, and levels of matrix metalloproteinase-3 and β-D-glucan exceeded reference values, at 140 ng/mL and 23.0 pg/mL, respectively. In addition, the platelet-associated IgG level increased to 50 ng/107, and the platelet count decreased to 73×109/L. Although blood bacterial cultures were negative and viral infection was ruled out, Enterobacter aerogenes was detected in the indwelling wound drain. Therefore, antibiotic therapy was continued, and the C-reactive protein level decreased to 1.19 mg/dL 2 weeks later (Figure 5).

The subsequent course of the patient was excellent. Postoperative contrast-enhanced CT confirmed good graft patency. Apart from fever, the patient experienced no complications and was discharged on postoperative day 20. At the 18-month follow-up, the patient had no recurrence of angina. During this period, he underwent 2 courses of radiation therapy, resulting in normalization of his thyroid function.

The Clinical Ethics Committee of Juntendo Nerima Hospital approved this study (approval number: S25-04). The study was conducted in accordance with the principles of the Declaration of Helsinki. The data associated with this manuscript are not publicly available; however, relevant data and images are preserved in the medical information system of the hospital and can be made available by the corresponding author upon reasonable request.

Discussion

The clinical issues in this case included the following: (1) uncontrolled hyperthyroidism identified before surgery, (2) the timing of CABG, and (3) the administration of plasma exchange therapy and IVIG for stabilizing thyroid function during the perioperative period.

Thyroid storm can be triggered by surgery, necessitating maximum perioperative precautions. We successfully stabilized thyroid function and facilitated coronary revascularization through the combined use of high-dose steroids, continuous slow plasma exchange, and IVIG during the perioperative period of CABG.

For overt hyperthyroidism, 3 to 8 weeks of thiamide therapy is recommended preoperatively [9]. In more severe thyrotoxicosis, the use of iodine or steroids can also be considered, to achieve near-hypothyroid status prior to surgical intervention [9,10]. These strategies are effective for managing preoperative hyperthyroidism [9]. Thyroid crisis is a life-threatening condition characterized by an excessive exacerbation of the clinical symptoms of thyrotoxicosis [2]. It frequently presents as sinus tachycardia or atrial fibrillation in approximately 10% to 25% of patients, which is an important precursor symptom [8,11]. The incidence of heart failure has been reported as 6% [10]. Fortunately, these symptoms tend to improve markedly as thyroid function normalizes [10].

Thyroid storm, a life-threatening condition, is characterized by exaggerated clinical manifestations of thyrotoxicosis [2]. It presents as sinus tachycardia or atrial fibrillation in approximately 10% to 25% of patients, serving as a critical prodromal symptom [11]. The diagnosis of thyroid storm is a complex process involving the use of the BWPS, a clinical symptom assessment score. The BWPS assesses prodromal symptoms and the severity of symptoms of multisystem organ failure [8]. Early initiation of treatment is crucial, as thyroid storms are associated with in-hospital mortality rates of approximately 4% to 10% [5,12].

In our case, although the patient did not develop thyroid storm, a BWPS score of 40 indicated a high risk of progression to postoperative thyroid storm, necessitating the implementation of comprehensive perioperative management strategies.

Thyroid suppressants are the most effective and commonly used treatment modality for hyperthyroidism; however, they are associated with significant adverse effects. Thyroid-suppressing drugs can lead to agranulocytosis, a serious and potentially life-threatening complication. The incidence rate of leukopenia was reported as 37.2 per 1000 person-years (0.7%) within 72 days of treatment initiation [13]. Discontinuation of the causative drug is necessary. An alternative therapy is radioactive iodine therapy, but this requires 1 to 2 months for treatment. In emergencies, thyroidectomy is considered the most effective option [5]. We requested a thyroidectomy from the otolaryngology department. However, due to the presence of severe triple-vessel coronary artery disease, the thyroidectomy was deemed inappropriate.

The internal medicine and anesthesiology departments recommended delaying surgery for 2 to 3 months to allow for stabilization of the thyroid function of the patient. However, the patient continued to experience resting chest pain after admission, which required continuous intravenous infusion of vasodilators and strict bed rest. Therefore, percutaneous coronary intervention was also considered as a semi-emergency option. Unfortunately, the coronary arteries showed complex and frequent lesions, which indicated a high risk of restenosis. Therefore, CABG was chosen as the preferred procedure. To avoid triggering a thyroid crisis through surgery, the maximum possible perioperative preventive measures were implemented.

We stabilized thyroid function during the CABG perioperative period by combining high-dose steroids, continuous low-flow plasma exchange, and IVIG, enabling successful CABG. Postoperative atrial fibrillation (POAF) occurs in approximately 15% of patients after CABG and is a significant risk factor both in the early postoperative period and the long term [14]. Management of POAF in the context of hyperthyroidism is complex and requires careful consideration [15].

When thyroidectomy is not an option, therapeutic plasma exchange is an immediate and effective treatment for severe thyroid storm complicated by cardiac and neurological dysfunctions. Thyroid storms are classified as Category II indications by the American Society for Fermentation and Apheresis [16]. Apheresis can rapidly improve symptoms by removing T3 and T4, which bind albumin, autoantibodies, catecholamines, and cytokines. Providing the patient with unbound albumin also creates binding sites for free thyroid hormones, further reducing their levels. A drawback of conventional plasma exchange is the simultaneous removal of catecholamines and other medications. After CABG, circulatory dynamics can become unstable. POAF occurs in approximately 15% of patients with CABG, making it a risk factor for secondary complications, such as postoperative heart failure and arterial embolism. Managing POAF in the context of hyperthyroidism is particularly challenging. Amiodarone, a common treatment for POAF, is undesirable because it contains iodine-rich benzofuran, which raises iodine levels. Furthermore, repeated therapeutic plasma exchange sessions have been reported to enhance therapeutic efficacy. To maintain stable hemodynamics, we performed therapeutic plasma exchange gradually while maintaining CHDF. In the present case, thyroid hormone levels decreased progressively and did not increase after normalization.

One previously reported case involved the use of antithyroid medication, which failed to normalize the thyroid function of the patient. The patient experienced heart failure and subsequently underwent urgent CABG with cardiopulmonary bypass. Despite experiencing recurrent episodes of tachycardia after being weaned off cardiopulmonary bypass, the thyroid function of the patient normalized, and heart rate was stabilized by postoperative day 4. However, due to the effects of cortisol administered for treatment, combined with the effect of cardiac surgery, the patient died from multiple organ failure related to pneumonia 8 days postoperatively [7]. In another case, a patient developed unexplained fever and tachycardia, leading to hemodynamic collapse after CABG [6]. Further investigation revealed a diagnosis of thyroid storm. In our case, drawing on previous reports that emphasized the importance of early normalization of thyroid function, we performed plasma exchange slowly over 12 hours. Furthermore, referring to reports emphasizing the need for infection prevention during plasma exchange and steroid use [17], IVIG was administered concurrently with antibiotics for infection prevention, yielding favorable results.

The strength of this case lies in the robust support from previous studies [5–7,16,17] and the meticulous planning of the procedures in consultation with a cardiovascular surgeon, anesthetist, and internist. However, a notable limitation was the lack of prior hospital visits by the patient, which prevented early diagnosis of the thyroid condition and the implementation of preventive measures. Furthermore, there is a lack of published data comparing the effectiveness of 2 methods of plasma exchange therapy: the standard 2- to 3-hour procedure using a conventional filter and the 12- to 24-hour slow procedure using CHDF for suppressing thyroid function.

Conclusions

In patients with ischemic heart disease who present with chest pain and tachycardia, hyperthyroidism can occasionally be a contributing factor. CABG should generally not be performed in cases of uncontrolled hyperthyroidism. Nevertheless, in extremely rare situations in which patients have severe triple-vessel coronary artery disease and experience recurrent angina attacks, CABG may become necessary if urgent treatment for hyperthyroidism is not feasible.

In our representative case, we implemented several critical interventions during the perioperative period of CABG, including emergency slow plasma exchange, high-dose corticosteroids, CHDF, and IVIG therapy. Fortunately, the patient did not experience a thyrotoxic crisis, and thyroid function stabilized. Even when urgent coronary artery revascularization is necessary, comprehensive evaluation and a multidisciplinary treatment plan are essential to identify the underlying thyroid pathology.