American Thyroid Association: Revised Guidelines for Hyperthyroidism, Thyrotoxicosis

The American Thyroid Association (ATA) has revised its guidelines for the treatment of thyrotoxicosis, including hyperthyroidism.¹

For the updated guidelines, the ATA convened a task force of 11 experts from North America, South America, and Europe to review evidence that has emerged in the 5 years since publication of the previous set of guidelines.

“There have been new developments in thyroid research, and the new guidelines reflect this, as well as changes in practice trends,” Marilyn Tan, MD, an endocrinologist and clinical assistant professor at Stanford University School of Medicine in California, told Endocrinology Advisor. “It is important to continue reassessing our routine practices to make sure we are optimizing patient safety, outcomes, and health care utilization.”

Notable Updates

In an interview with Endocrinology Advisor, Douglas S. Ross, MD, chair of the task force and professor of medicine at Harvard Medical School and co-director of the Thyroid Clinic at Massachusetts General Hospital in Boston, highlighted 5 of the major changes in the new guidelines, which consist of 124 recommendations.

1. New paradigms for determining the etiology of thyrotoxicosis that make use of thyrotropin receptor antibodies (TRAb)

“There is a shift away from starting with a radioactive iodine (RAI) uptake and scan as the first step for determining the etiology of thyrotoxicosis,” according to Dr Tan. If it is not evident from the clinical presentation and initial biochemical evaluation—as in the case of a patient with a nonnodular thyroid and no apparent orbitopathy, for example—then diagnostic testing should be conducted. This may include measurement of TRAb, radioactive iodine uptake, or ultrasonography to measure thyroidal blood flow.¹ A thyroid scan is indicated if toxic adenoma or toxic multinodular goiter is suspected.¹

2. The use of TRAb for monitoring the response to antithyroid drugs

Adverse effects of antithyroid drugs, which were found to affect an estimated 13% of patients in a systematic review,² range from minor allergic reactions to serious reactions that include agranulocytosis, vasculitis, and hepatotoxicity. According to the new guideline, such patients’ thyroid status should be monitored to inform any necessary dosage changes, and TRAb levels should be measured before the end of antithyroid drug therapy to identify patients with a higher chance of remission.¹

“Patients with persistently high TRAb could continue [antithyroid drug] therapy (and repeat TRAb after an additional 12-18 months) or opt for alternate definitive therapy with RAI or surgery,” wrote the authors.

3. Safety data supporting the use of long-term antithyroid drug therapy

“There is less of a push for definitive therapy for hyperthyroidism—such as radioactive iodine ablation or surgery,” said Dr Tan. “Previously, due to safety concerns, it was recommended that the time on antithyroid drugs be limited. It is now more accepted to be on antithyroid drugs long-term.”

In one study of patients with Graves’ disease, methimazole doses of 2.5 mg/d to 10mg/d taken for a mean duration of 14 years were found to be safe and effective,³ and another study reported that long-term use of low-dose antithyroid drugs resulted in better outcomes and fewer side effects than RAI.⁴

4. New paradigms for managing women with hyperthyroidism planning pregnancy in the near future

Several of the recommendations address concerns pertaining to pregnancy in women with hyperthyroidism in their reproductive years. The authors suggest that such patients postpone pregnancy until they achieve euthyroid levels.¹ When choosing the therapeutic approach for patients who are pregnant or may become pregnant, clinicians should consider potential maternal and fetal risks of both thyroid dysfunction and the medication.¹ Because a single set of thyroid tests may not be sufficient, it is preferable to conduct 2 sets of tests at least 1 month apart.¹ “In addition, there is more emphasis on following antibodies throughout pregnancy in a woman with Graves’ disease,” Dr Tan pointed out.

5. New data regarding the importance of optimizing calcium and vitamin D prior to thyroid surgery

“Due to the risk of postsurgical hypoparathyroidism, there are now more formal recommendations to optimize calcium and vitamin D before surgery,” noted Dr Tan.

The authors highlight findings from several recent studies showing that preoperative oral supplementation with these nutrients reduced rates of postoperative hypocalcemia. One study, for example, found that patients with preoperative serum 25-hydroxyvitamin D levels greater than 20 ng/mL (greater than 8 nmol/L) had lower rates of hypocalcemia after surgery,⁵ while other research showed that treatment with oral calcium in the 2 weeks before thyroidectomy was associated with lower postoperative rates of hypocalcemia in patients with Graves’ disease.⁶

Looking Ahead

As for next steps in terms of research priorities in this area, Dr Ross said, “We need large treatment trials to determine which patients need to be treated for subclinical hyperthyroidism, and we need better treatments for Graves’ orbitopathy.”

Dr Tan believes the new guidelines are quite comprehensive.

“As with the prior version, it is helpful that the guidelines explore the various potential causes and clinical consequences of untreated thyrotoxicosis to help physicians better understand the pathophysiology of the disease and how to take an individualized approach to treatment,” she stated. 

References

1. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. Thyroid. 2016;26(10):1343-1421.
2. Sundaresh V, Brito JP, Wang Z, et al. Comparative effectiveness of therapies for Graves’ hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2013;98(9):3671-3677.
3. Azizi F, Yousefi V, Bahrainian A, Sheikholeslami F, Tohidi M, Mehrabi Y. Long-term continuous methimazole or radioiodine treatment for hyperthyroidism. Arch Iran Med. 2012;15(8):477-484.
4. Villagelin D, Romaldini JH, Santos RB, Milkos AB, Ward LS. Outcomes in relapsed Graves’ disease patients following radioiodine or prolonged low dose of methimazole treatment. Thyroid. 2015;25(12):1282-1290.
5. Kim WW, Chung SH, Ban EJ, et al. Is preoperative vitamin D deficiency a risk factor for postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing total thyroidectomy plus central compartment neck dissection? Thyroid. 2015;25(8):911-918.
6. Oltmann SC, Brekke AV, Schneider DF, Schaefer SC, Chen H, Sippel RS. Preventing postoperative hypocalcemia in patients with Graves disease: a prospective study. Ann Surg Oncol. 2015;22(3):952-8.