Dr. Riccardo Dore (left) and Prof. Jens Mittag (right), first and last authors of the study, analyze cardiac data. (Photo: Nuria López Alcántara)

It is well established that high levels of thyroid hormone cause elevated heart rate. However, patients with a mutation in their thyroid hormone receptor are surprisingly resistant against this effect. Researchers of the Institute of Endocrinology and Diabetes at the “Center of Brain Behavior and Metabolism” (CBBM) have now unraveled the underlying molecular mechanism in the corresponding animal model.
„We learnt from our colleagues in Cambridge that their patients with a mutation in thyroid hormone receptor alpha, which they routinely treat with high doses of thyroxine, did not respond with elevated heart rate”, elaborates Prof Jens Mittag, leader of the study published in the prestigious journal “Nature Communications”. “We were able to replicate this finding in our corresponding animal model, which allowed us in depth studies. These studies revealed that the heart has a defect due to the mutation, which arises already during embryonal development. As a consequence, several cardiac ion channels are no longer regulated by thyroid hormone leading to the observed resistance.”
„Most interestingly, the regulation of two important pacemaker channels is still intact in the animals, which demonstrates that these channels are not the sufficient to elevate heart rate”, adds Dr. Riccardo Dore, first author of the study. “Given that current textbooks assign the elevated heart rate in hyperthyroidism to these two channels, this aspect of cardiac thyroid hormone action needs to be rewritten.”
Find the publication here.