What is the association between atrial fibrillation and thyrotoxicosis in a patient with hypothyroidism taking an excessive dose of Levothyroxine (levothyroxine)?

From the Guidelines

Atrial fibrillation is strongly associated with thyrotoxicosis in patients with hypothyroidism taking excessive doses of Levothyroxine, and management involves reducing the levothyroxine dose and possibly using beta-blockers to control heart rate. When a patient takes too much levothyroxine, they develop elevated thyroid hormone levels that mimic hyperthyroidism or thyrotoxicosis, which can lead to atrial fibrillation due to increased beta-adrenergic activity in the heart, enhanced automaticity and excitability of cardiac tissue, and shortened refractory period of cardiac myocytes 1. Key points to consider in management include:

• Reducing the levothyroxine dose to achieve normal thyroid function tests (TSH and free T4 within normal range)
• Possibly using beta-blockers temporarily to control heart rate while thyroid levels normalize, as recommended for patients with AF complicating thyrotoxicosis 1
• Regular monitoring of thyroid function tests is essential when adjusting levothyroxine dosage to prevent both under-replacement and over-replacement complications. In terms of antithrombotic therapy, administration of a β-blocker is recommended to control the rate of ventricular response in patients with AF complicating thyrotoxicosis, unless contraindicated 1. Additionally, if a rhythm control strategy is desirable, it is necessary to normalize thyroid function prior to cardioversion, as otherwise the risk of relapse remains high 1. Overall, the goal is to restore a euthyroid state and manage atrial fibrillation accordingly, taking into account the patient's individual risk factors and medical history.

From the FDA Drug Label

Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease:Initiate levothyroxine sodium at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation. Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly. Adverse reactions associated with levothyroxine sodium therapy are primarily those of hyperthyroidism due to therapeutic overdosage: arrhythmias, myocardial infarction, dyspnea, muscle spasm, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash

The association between atrial fibrillation and thyrotoxicosis in a patient with hypothyroidism taking an excessive dose of Levothyroxine is that atrial fibrillation is a potential adverse reaction due to overtreatment with levothyroxine sodium, which can lead to thyrotoxicosis. This is particularly relevant in elderly patients or those with underlying cardiovascular disease. Key factors to consider include:

• Dose adjustment: Initiating levothyroxine sodium at less than the full replacement dose to minimize the risk of cardiac adverse reactions.
• Monitoring: Regularly monitoring patients for signs of overtreatment, including arrhythmias and other symptoms of hyperthyroidism.
• Patient population: Being aware that elderly patients and those with cardiovascular disease are at increased risk of atrial fibrillation due to levothyroxine overtreatment 2, 2, 2.

From the Research

Association between Atrial Fibrillation and Thyrotoxicosis

• Atrial fibrillation is a common cardiac complication of hyperthyroidism, occurring in 15% of patients with hyperthyroidism 3.
• Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism 4.
• The presence of excess thyroid hormone alters adrenergic receptors in the heart and blood vessels, leading to an increase in sympathetic function and atrial fibrillation 5.

Levothyroxine Overdose and Thyrotoxicosis

• Even a slight overdose of levothyroxine carries a risk of osteoporotic fractures and atrial fibrillation, especially in the elderly 6.
• The adverse effects of levothyroxine are signs of thyrotoxicosis in case of overdose, including tachycardia, tremor, sweating, etc. 6.

Management of Thyrotoxicosis-Induced Atrial Fibrillation

• Early and monitored treatment and follow-up of hyperthyroidism is key to the management of atrial fibrillation and heart failure in achieving a better outcome 7.
• Propranolol should be used over metoprolol in patients with hyperthyroidism-induced atrial fibrillation due to its effect on blocking the activity of T4 conversion to active T3 5.
• Beta-blockers offer symptomatic relief and slow the ventricular response in patients with atrial fibrillation 4.