Management of Graves Disease: Shift Is Occurring

A 2011 Survey of Clinical Practice Patterns in the Management of Graves' Disease

Burch HB, Burman KD, Cooper DS
J Clin Endocrinol Metab. 2012;97:4549-4558

Article Summary

Graves disease is the most common cause of endogenous hyperthyroidism and may be associated with clinical symptoms that include nervousness, weight loss, anxiety, tremor, or ophthalmic complaints (eg, burning, itching, diplopia). Graves disease is caused by stimulating antibodies that are directed against thyroid-stimulating hormone (TSH) receptors, which mediate unabated enhanced synthesis and secretion of T3 and T4.

The precise mechanism by which these immunoglobulins develop is unknown.^[1,2] The treatment of thyrotoxicosis in a patient with Graves disease involves long-term use of antithyroid agents (preferably methimazole), radioactive iodine therapy, or thyroidectomy. Few relevant clinical studies have directly compared the effectiveness of each therapy, and in many cases the treatment of choice is a result of discussion between the patient and physician.

A recent article by Burch and colleagues^[3] updated information on the geographical differences in the treatment approach for patients with Graves disease and hyperthyroidism. The authors surveyed members of The Endocrine Society, American Thyroid Association, and American Association of Clinical Endocrinologists on their preference of treatment options and factors that might alter this approach. In total, 696 surveys were analyzed. The survey included several patient scenarios, after which questions were asked about how the clinician would approach each particular patient care issue.

For patients with uncomplicated Graves disease and hyperthyroidism, 53.9% of respondents indicated that they would initially treat the patient with antithyroid agents, 45.0% chose radioactive iodine, and 0.7% thyroidectomy. Earlier articles state that radioactive iodine therapy is favored as definitive therapy in the United States, whereas in Europe and Japan, antithyroid agents are preferred.^[1,2,4] Responses from the survey were compared with a survey from 1991,^[4] and it was found that, surprisingly, initial radioactive iodine therapy is now recommended less frequently in the United States and Europe. Indeed, the assessment and management of Graves disease varied widely geographically.^{[5,6,7,8,9,10,11,12]}

The percentages of respondents recommending radioactive iodine as the initial modality of treatment were 58.6% in North America, 13.3% in Europe, 26.3% in Latin America, 29.4% in Asia/Oceania, and 33.3% in the Middle East. Almost all of the respondents would recommend antithyroid agents if they did not initially prefer radioactive iodine therapy. A thyroidectomy was recommended in only 1% or less of all respondents. Of respondents who were using antithyroid treatment, 97.3% would prescribe methimazole (or carbimazole), compared with 2.7% of respondents who would initially use propylthiouracil. Radioactive iodine therapy was recommended less frequently than antithyroid agents or surgery for patients with Graves ophthalmopathy.

If antithyroid agents were chosen as initial therapy, approximately 90% of respondents said that they would assess thyroid function within 6 weeks of initiating therapy. After euthyroidism is achieved, about 62% of physicians said that they would check thyroid function at 3-month intervals, 48.4% would monitor serial complete blood counts (CBC), and 53.8% would monitor liver function tests; 40.2% of respondents do not recommend monitoring either CBC or liver-associated enzymes. In an effort to induce remission, only 13.9% of respondents would treat for less than a year, 30.2% for 1 year, and 19.3% for 2 years.

In the group that chose radioactive iodine as the initial therapy, 12.7% do not routinely use antithyroid agents to prepare the patient prior to radioactive iodine therapy, 37.7% routinely treat most patients with antithyroid agents in this circumstance, and 49.6% use antithyroid agents selectively in patients who may have other medical issues such as underlying cardiac disease, multiple comorbidities, or if they are older than 65 years of age.

In a patient with hyperthyroidism who was going to undergo a thyroidectomy, 91.2% of physicians would recommend that the patient be given antithyroid agents prior to surgery to normalize their thyroid function tests. Saturated solution of potassium iodide or Lugol's solution would be used by 37% of respondents prior to surgery.

In the index case of an uncomplicated patient with Graves disease, baseline CBC would be obtained by 49.7% of respondents, liver function tests by 47.9%, thyroid-stimulating immunoglobulin by 52.1%, and thyroid-binding inhibitory immunoglobulin by 16.1%. A radioactive iodine uptake test would be obtained by 47%, thyroid isotope scan by about 42%, and a thyroid sonogram by 25.8%.

Respondents were then queried to determine how they would manage a patient who had a clinical presentation different from the initial uncomplicated case of Graves disease. If the patient had active Graves ophthalmopathy, 62.8% of respondents would select long-term antithyroid agents, 18.5% would select thyroidectomy, and 16.9% would recommend radioactive iodine therapy with concomitant corticosteroid administration. In a female patient with Graves disease who was planning to become pregnant within the next 6-12 months, 49.9% of physicians would recommend antithyroid agents, 29.8% would recommend radioactive iodine therapy, and 20.3% would recommend a thyroidectomy. Propylthiouracil was preferred by 54.3% of physicians for treating patients who are planning pregnancy; 45.7% preferred methimazole. Of the group recommending methimazole, 75.6% would switch to propylthiouracil when pregnancy is confirmed. If propylthiouracil was employed in the first trimester of pregnancy, 54.1% would not recommend switching to methimazole at the beginning of the second trimester.