MCT8-AHDS Foundation

High T3, low T4 serum levels in Mct8‐deficiency are not caused by increased hepatic conversion through type I‐deiodinase

Eva K. Wirth, Eddy Rijntjes, Franziska Meyer, Josef Köhrle, Ulrich Schweizer

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein
monocarboxylate transporter 8 (MCT8).
To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I-deiodinase (Dio1).

We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results: Inactivation of Dio1 activity in the livers of global Mct8- deficient mice does not restore normal circulating thyroid hormone levels. Conclusions: Our data suggest that, although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.