A 36-year-old woman comes to the office due to weight loss. She has lost 5 kg (11 lb) over the last 3 months associated with palpitations, heat intolerance, persistent tremors, and excessive sweating. Past medical and family histories are unremarkable, and the patient does not use tobacco, alcohol, or illicit drugs. She is married and has a child. Blood pressure is 140/70 mm Hg and pulse is 104/min and regular. Physical examination shows a 2x2 cm nodule in the left thyroid lobe. The rest of the thyroid gland is normal, and there is no associated cervical lymphadenopathy. Eye examination shows minimal lid lag, but no proptosis or chemosis. There is a fine tremor in both upper extremities. Thyroid function test results are as follows:
Serum TSH <0.03 µU/mL Total T3 330 ng/dL Total T4 14 µg/dL
Radioactive iodine scan shows uptake only in the nodule. The patient wishes to have additional children and is concerned that she will not be able to get pregnant if she is treated for her current condition. If left untreated, this patient is at greatest risk for developing which of the following complications?
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This patient with hyperthyroid symptoms, suppressed TSH, and a "hot" thyroid nodule has typical features of a toxic adenoma (TA). TA and toxic multinodular goiter (MNG) are the most common causes of hyperthyroidism after Graves disease and are most often caused by activating mutations in the TSH receptor. These disorders are characterized by TSH-independent thyroid hormone secretion and focal (TA) or multifocal (MNG) follicular hyperplasia. Initial treatment of TA and MNG includes a beta blocker to alleviate the symptoms of hyperthyroidism and a thionamide (eg, methimazole, propylthiouracil) to decrease thyroid hormone secretion. Options for definitive management of TA include surgery and radioiodine ablation.
If left untreated, patients with hyperthyroidism can develop rapid bone loss leading to osteoporosis and increased risk of fracture. Direct effects of the thyroid hormones cause increased osteoclastic bone resorption. Patients can also develop hypercalcemia and hypercalciuria due to increased bone turnover.
(Choice B) Common cardiovascular effects of hyperthyroidism include tachycardia, systolic hypertension, increased pulse pressure, and tachyarrhythmias (eg, atrial fibrillation). Thyrotoxicosis per se is not a risk factor for coronary artery disease, although its symptoms can be unmasked or worsened with thyrotoxicosis.
(Choice C) Fetal hyperthyroidism can be seen in patients with active Graves disease, in whom TSH receptor (TSHR) antibodies can cross the placenta and affect the fetal thyroid. TSHR antibodies are not seen in TA.
(Choice D) Large hypofunctioning ("cold") nodules carry an increased risk of malignancy and require additional evaluation. Hyperfunctioning nodules are rarely malignant.
(Choice E) Infiltrative ophthalmopathy in Graves disease leads to proptosis, impaired ocular movement, ocular irritation and redness, and possible vision loss. However, significant ophthalmopathy is not seen in TA.
Educational objective:
Untreated hyperthyroid patients are at risk for rapid bone loss from increased osteoclastic activity in the bone cells. Untreated hyperthyroid patients are also at risk for cardiac tachyarrhythmias, including atrial fibrillation.