Although the thyroid gland secretes a very small amount of active thyroid hormone (triiodothyronine or T ), the major circulating form is thyroxine (T4), and it is widely accepted that thyroid hormone replacement in patients with hypothyroid- ism can be fully accomplished with L-T4 monotherapy [see 1995 American Thyroid Association guidelines (Ref. 1)]. The mech- anistic basis for this belief stems from the actions of the iodo- thyronine deiodinases, enzymes that activate thyroid hormone by conversion of T4 to T3 (or inactivate both forms via further deiodination) (2). Thanks to the actions of the type 2 deiodinase (D2) and to some extent the type 1 deiodinase (D1), both en- dogenous T4 and L-T4 are converted to T3 at a rate sufficient to maintain normal serum T3 concentration. However, despite the extensive literature demonstrating that patients do well clinically on L-T4 monotherapy, most clinicians have at least anecdotally seen benefits from combined T3/T4 therapy for some patients, prompting a search for the biological mechanism of the T3 re- quirement. In the current issue of JCEM, Panicker et al. (3) examine this question from a novel perspective, asking whether a polymorphism in the Dio2 gene could explain a differential psychological response to the type of thyroid hor- mone replacement seen in a subpopulation of the Weston Area T4/T3 Study (WATTS) from the United Kingdom (3, 4).

For Some, L-Thyroxine Replacement Might Not Be Enough: A Genetic Rationale.

Brian W. Kim and Antonio C. Bianco.Journal of Clinical Endocrinology and Metabolism. May, 2009; doi: 10.1210/jc.2009-0410

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