3 years ago

THERAPY OF ENDOCRINE DISEASE: T4+T3 COMBINATION THERAPY: IS THERE A TRUE EFFECT?

5-10% of hypothyroid patients on T4 replacement have persistent symptoms, despite normal TSH levels. T4+T3 combination therapy provided no better outcomes according to a meta-analysis of 11 randomized clinical trials comparing T4 monotherapy with T4+T3 combination therapy. This review evaluates recent developments in the field of T4+T3 therapy . T4 monotherapy is associated with higher serum FT4 and lower serum FT3 and FT3/FT4 ratio's than in healthy subjects. T4+T3 combination therapy may mimic more closely thyroid function tests of healthy subjects, but it has not been demonstrated that relatively low serum FT3 or FT3/FT4 ratio's are linked to persistent symptoms. One study reports polymorphism Thr92Ala in DIO2 is related to lower serum FT3 levels after thyroidectomy, and that the D2-Ala mutant reduces T4 to T3 conversion in cell cultures. Using peripheral tissue function tests of thyroid hormone action, patients with normal TSH during T4 monotherapy, were mildly hypothyroid , whereas those with TSH 0.03-≤0.3 mU/L were closest to euthyroidism. These biomarkers suggested euthyroidism more frequently in patients randomized to T4+T3 rather than to T4. Preference for T4+T3 over T4 monotherapy was dose-dependently related to the presence of two polymorphisms in MCT10 and DIO2 in one small study. The number of patients on T4+T3 therapy has multiplied in the last decade, likely induced by indiscriminate statements on the internet. Patients are sometimes not just asking but rather demanding T4+T3 treatment. It creates tensions between patients and physicians. Only continued research will solve.

Publisher URL: http://doi.org/10.1530/EJE-17-0645

DOI: 10.1530/EJE-17-0645

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