Treatment of Hypothyroidism: Possibilities on the Horizon

Abstract

We would like to invite you to attend the upcoming spring symposium ‘‘Treatment of Hypothyroidism: Exploring the Possibilities.’’ We hope you will share the enthusiasm of the organizing committee regarding our exciting spectrum of topics and speakers. Although thyroid hormone therapy is by no means in its infancy, many aspects of its use are prescient and remain the subject of debate. We have progressed from the use of dried thyroid glands by ancient Chinese cultures (1), to the pioneering use of thyroid extracts given subcutaneously or orally in the 1890s (2), to the routine use of desiccated porcine or bovine thyroid preparations, and their subsequent replacement by synthetic levothyroxine during the mid-1970s (3). The expectation that use of levothyroxine would provide complete resolution of the constellation of symptoms that characterize hypothyroidism was a reasonable, but nevertheless overly optimistic, hope. Revolutionary though the availability of convenient, effective, and reliable synthetic thyroid hormone preparations has been, the specter of incomplete resolution of all symptoms associated with the hypothyroid condition has not left us. Individuals with hypothyroidism and normal thyrotropin (TSH) values may have less psychological well-being (4–6) and more fatigue (7) than individuals without thyroid disease. Some (8,9), but not all (10), studies suggest that serum triiodothyronine (T3) may be lower in levothyroxine-replaced patients than in the euthyroid population. Trials of combined therapy with both thyroxine (T4) and T3 in unselected populations have generally been disappointing (11–14). The seeming irreversibility of some ramifications of hypothyroidism may potentially be explained by the existence of genetic variations in deiodinases, TSH receptors, and thyroid hormone transporters (15–17). Our understanding of how such discoveries should influence our approach to the treatment of hypothyroidism will be advanced by adequately powered, prospective trials of the response of individuals harboring these genetic variations to specific therapies. Randomized, blinded, rigorously conducted, within-individual comparisons of therapy that can be subjected to metaanalysis may also advance our understanding (18). Through such means, the options of both synthetic and natural combination therapies will continue to be investigated. The possibility that some thyroid derivatives such as thyronamines have physiologic roles may need to be considered (19). Although there has been a hiatus since such products were reported in the literature (20), preparations of T3 with a physiologic extended-release profile are also under development and may be one of our options for therapy in the future. Stem cell technology may also be applied in the future to reverse the athyreotic state (21). As we learn more about the complexities of treating this condition, we are also learning that seemingly simple aspects of therapy such as achieving acceptable adherence to prescribed therapy and maintaining a TSH value within a desired target range cannot always be accomplished (22–24). In addition, different patient groups may require different approaches. Treating hypothyroidism in the elderly (24), for example, may not require the same therapeutic goals and frequency of monitoring as treatment of other populations such as those who are pregnant (25,26). In conjunction with the work of the American Thyroid Association Task Force on Thyroid Hormone Replacement and Use of Thyroid Hormone Analogues, we have organized a spring meeting that is devoted to these topics. We hope this meeting, scheduled in Washington, DC, on April 25 and 26, will be a forum conducive to exploring new research developments affecting these issues. As a starting point, the symposium will have a half-day of basic science that will review