A 48-year-old woman comes to the office for follow-up of primary hypothyroidism due to chronic autoimmune (Hashimoto) thyroiditis. She feels well and has no palpitations, heat/cold intolerance, diarrhea/constipation, or changes in weight. The patient takes levothyroxine daily on an empty stomach. She has no other medical conditions and takes no other medications. The patient has no drug allergies and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 120/70 mm Hg and pulse is 72/min. BMI is 27 kg/m2. On physical examination, the thyroid is normal to palpation. There is no peripheral edema. Laboratory results show a serum TSH level of <0.01 µU/mL. Maintaining the current dose of levothyroxine would put this patient at the greatest risk for which of the following complications?
Cardiovascular effects of hyperthyroidism | |
Increased rate |
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Increased contractility |
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| Peripheral vasodilation |
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Additional effects |
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This patient is on thyroid replacement therapy for hypothyroidism and has a suppressed TSH (normal range: 0.5 to 5.0 µU/mL), indicating that her current dose is too high. Excess thyroid hormone, whether due to endogenous hyperthyroidism or iatrogenic over-replacement with levothyroxine, causes increased beta-adrenergic receptor expression. The resulting hyperadrenergic state can lead to significant cardiovascular complications.
Thyrotoxicosis is associated with hypertension, tachycardia, and increased myocyte automaticity. Atrial fibrillation is the most common supraventricular arrhythmia and is a frequent complication of thyrotoxicosis. Thyrotoxicosis also increases contractility, which increases myocardial oxygen demand and can precipitate angina in patients with underlying coronary disease. It can also increase cardiac output (while also decreasing systemic vascular resistance) and lead to high-output heart failure. Therefore, even though this patient feels well, her dose of levothyroxine should be reduced to avoid long-term complications of over-replacement.
(Choices A and E) Agranulocytosis is a potential complication of thionamide antithyroid drugs (eg, propylthiouracil, methimazole). Propylthiouracil can also cause hepatotoxicity. However, levothyroxine used in thyroid replacement therapy does not cause these complications.
(Choice C) Thyroid over-replacement can cause insomnia and affective symptoms (eg, anxiety, irritability). Although hyperthyroidism in elderly patients may manifest as social withdrawal and slowed responses (apathetic depression) resembling dementia, cognitive dysfunction in younger patients is more likely to be seen in hypothyroidism rather than in hyperthyroidism.
(Choice D) The goiter seen in hypothyroidism is due to chronic thyroid stimulation by TSH. This manifestation improves with the administration of levothyroxine (as TSH levels are decreased) and is not seen in over-replacement.
(Choice F) Thyroid cancer is a potential long-term complication of radioiodine therapy for hyperthyroidism.
Educational objective:
Thyrotoxicosis, whether due to endogenous hyperthyroidism or over-replacement with thyroid hormone in patients with hypothyroidism, causes a hyperadrenergic state that can lead to atrial fibrillation, high-output heart failure, and worsening of angina pectoris.