Background: Most endocrinologists encounter patients who are dissatisfied with their current hypothyroidism therapy and request combination therapy with either liothyronine (LT3) or thyroid extract.
Methods: A survey of American Thyroid Association members was conducted in 2017. Respondents were presented with 13 scenarios describing patients with hypothyroidism and were asked to choose among six therapeutic options. The index patient was satisfied taking levothyroxine (LT4) therapy. Twelve variations introduced parameters that potentially provide reasons for considering combination therapy (presence of symptoms, low serum triiodothyronine concentration, documentation of deiodinase polymorphisms). Therapeutic options included (i) continuing LT4, (ii) increasing LT4, (iii) adding LT3 to a reduced LT4 dose, (iv) adding LT3 to the current LT4 dose, (v) replacing LT4 with thyroid extract, and (vi) replacing LT4 with LT3. Repeated-measures logistic regression analysis was performed to examine both the prescribing of LT4 (options i and ii) versus all other therapies and the choice of continuing LT4 (option i) versus either increasing LT4 (option ii), adding LT3 (options iii and iv), or replacing LT4 with thyroid extract or LT3 (options v and vi).
Results: Of the 389 survey respondents, 363 physicians prescribed therapy for hypothyroidism. For the index patient, 98% of physicians continued current LT4 therapy. However, as the patient scenario incorporated other patient characteristics, physicians opted to increase LT4 dose or prescribe other therapies. The tendency to prescribe alternative therapies was powerfully increased by patient symptoms (odds ratio = 25.6 [confidence interval 9-73], p < 0.0001). Older age and the presence of a comorbidity reduced the likelihood that an alternative therapy was prescribed (p = 0.0002 and <0.0001, respectively). All other characteristics, except athyreotic status, patient sex, and body mass index, significantly increased the likelihood that alternative therapies would be prescribed in multivariate analyses (p < 0.0001).
Conclusions: Even with the acknowledged limitations of survey methodology, this analysis appears to show a marked increase in the willingness of physicians to prescribe combination therapy in specific circumstances. If current prescribing patterns do incorporate the use of therapies other than LT4, there is a critical need for more research into the benefits and risks of these therapies.
Keywords: combination therapy; hypothyroidism; liothyronine; physician prescribing; thyroid extract.