Graves hyperthyroidism

Thyroid eye disease (TED) is discussed in BCSC Section 5, Neuro-Ophthalmology, and Section 7, Oculofacial Plastic and Orbital Surgery. This section focuses on the thyroid disease.

Patients with Graves hyperthyroidism (also known as diffuse toxic goiter) exhibit various combinations of hypermetabolism, diffuse enlargement of the thyroid gland, TED, and infiltrative dermopathy. Graves hyperthyroidism is an autoimmune disorder. Up to 90% of patients have circulating TSH receptor antibodies; furthermore, the level of TSI has been shown to correlate with the severity of clinical disease.

Graves hyperthyroidism is common, with a lifetime risk of 3.0% for women and 0.5% for men. The incidence peaks in the third to fifth decades of life, and there is a strong familial component. Risk factors including stress and smoking are associated with increased incidence of thyroid eye disease.

Common clinical symptoms include fatigue, tremor, weight loss, palpitations, and heat intolerance. Manifestations can vary by age of patient at the onset of hyperthyroidism. For instance, atrial fibrillation is rare in patients younger than 60 years but occurs in more than 10% of patients 60 years or older. A palpable goiter develops in most patients younger than 60 years old compared with less than 50% of patients older than 60 years. Approximately one-third of patients with Graves hyperthyroidism have clinically obvious TED at the time of diagnosis of the hyperthyroidism.

Treatment of Graves hyperthyroidism is aimed at returning thyroid function to normal. A significant proportion of patients (30%–50%) experience remission in association with drug treatment directed at the thyroid. Later in the course of the disease, patients may experience relapse, hypothyroidism, or both.

Thyroid secretion is suppressed using one of the thiourea derivatives, propylthiouracil or methimazole. The drugs inhibit the use of iodine by the gland. Treatment is continued until clinical and laboratory indexes show improvement. Adverse effects include rash (common), liver damage (rare), vasculitis (rare), and agranulocytosis (occurs in 0.02%–0.05% of patients).

There are several options for long-term management of Graves hyperthyroidism: the aforementioned antithyroid drugs can be continued for 12–24 months in hopes of remission; part of the gland can be surgically removed, although approximately half of such patients eventually become hypothyroid; or radioactive iodine can be used. Iodine 131 (¹³¹I) is highly effective, resulting in hypothyroidism in 80% of patients within 6–12 months; some require a second treatment. Although adverse effects of ¹³¹I are minimal, its use is associated with worsening of TED.

Ophthalmic considerations A new drug, teprotumumab, has been shown to slow progression of ophthalmopathy in patients with moderate to severe thyroid eye disease and is currently undergoing clinical trials. The drug, which inhibits insulin-like growth factor I receptor, represents a new therapeutic strategy for treating the underlying autoimmune pathogenesis of TED. Teprotumumab has been granted orphan drug status by the US Food and Drug Administration, and clinical trials will determine if it slows the progression of ophthalmopathy in patients with newly diagnosed TED.

• Smith TJ, Hegedüs L. Graves’ disease. N Engl J Med. 2016;375(16):1552–1565.

• Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748–1761.

Toxic nodular goiter

In toxic nodular goiter, thyroid hormone–producing adenomas (either single or multiple) make enough hormone to cause hyperthyroidism. These so-called hot nodules are almost never carcinomatous and often result in hyperthyroidism. Toxic nodules may be treated with radioactive iodine or surgery.

Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.