Antithyroid Drugs in the Management of Patients with Graves’ Disease: An Evidence-Based Approach to Therapeutic Controversies

Antithyroid drugs have been in use for over half a century, and much is now known about their mechanism of action, pharmacokinetics, and clinical pharmacology (1). Somewhat surprisingly perhaps, clinicians are still challenged on a regular basis by numerous questions related to their optimal use. Choice of antithyroid agent, duration of use, proper dosage, patient selection for primary antithyroid drug therapy, and pretreatment of patients before radioiodine administration are just some of the issues that confront busy practitioners on an almost daily basis. Although there have been published guidelines addressing the general subject of hyperthyroidism therapy (2–4), they are not evidenced-based, nor do they confront these specific, practical questions. To try to address these specific issues in a rigorous way, the following discussion will use an evidence-based approach. The American Academy of Family Physicians (5) and most other organizations rate levels of evidence according to the following scheme. • Level A: a high-quality randomized controlled trial (RCT) that considers all important outcomes, and high-quality metaanalysis (quantitative systematic review) using comprehensive search strategies. • Level B (other evidence): a well-designed, nonrandomized clinical trial; and a nonquantitative systematic review with appropriate search strategies and well-substantiated conclusions. Level B includes lower quality RCTs, clinical cohort studies, and case-controlled studies with nonbiased selection of study participants and consistent findings. Other evidence, such as high-quality, historical, uncontrolled studies, or well-designed epidemiological studies with compelling findings, is also included. • Level C: consensus viewpoint or expert opinion. The cases of two prototypical patients that are likely to be seen frequently in any busy clinical endocrinologist’s office will be presented. A series of questions about each case will be raised and then answered using level A evidence, wherever possible. Unfortunately, for many of the questions under consideration, the highest levels of evidence are not available, and data that are less rigorously obtained must be used. A 1998 British review (6) discussed some of the same issues using a similar format.