New aspects of an old dilemma: treatment of hypothyroidism with L-thyroxine combined with L-triiodothyronine

Abstract

The current review summarizes the most recent developments in the field of combined treatment with LT4+LT3 in hypothyroidism. Though it was well established for the past 20 years that T3 combined with T4 was best able to achieve euthyroidism in hypothyroidectomized rats, several recent studies and meta-analyses did not demonstrate any increased benefit of combined treatment as compared with T4 monotherapy. Moreover, patients under combination treatment are more prone to experience adverse effects, such as tachycardia, nervousness and fatigue. Conversely, T4 monotherapy usually leads to lower FT3 and higher serum FT4 levels as compared to the LT4+LT3 regimen thus resulting in a FT3:FT4 ratio closer to that of healthy subjects. Today, T4 monotherapy constitutes first-line treatment of hypothyroidism according to both the ETA and ATA Guidelines. However, in many cases the guidelines are not followed, with patients often taking compounded desiccated thyroid hormones or various T3 preparations available on the web. Recently, single nucleotide polymorphisms (SNPs) in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes and in the phosphodiesterase 8B gene have been associated with T3 decrease and thyroid dysfunction. The above observations point to the necessity for more research into the application of customized treatment as well as to the need for the long-awaited LT3-retard formulations or low-dose (about 5g/tablet/capsule) LT3 preparations to be appropriately dosed with LT4 in the context of a personalized treatment strategy. The recent finding that SNPs in DIOs or in thyroid hormone transporter genes may affect serum T3 in tissues opens up the way to the genotyping of those thyroidectomized patients who complain of symptoms and have a lower FT3:FT4 ratio.

Keywords

• l-thyroxine
• l-triiodothyronine
• hypothyroidism
• single nucleotide polymorphisms (snps)
• thr92ala
• ft3:ft4 ratio