Thermoregulatory and Cardiovascular Consequences of a Transient Thyrotoxicosis and Recovery in Male Mice

Endocrinology. 2016 Jul;157(7):2957-67. doi: 10.1210/en.2016-1095. Epub 2016 May 4.


Thyroid hormones play a major role in body homeostasis, regulating energy expenditure and cardiovascular function. Given that obese people or athletes might consider rapid weight loss as beneficial, voluntary intoxication with T4 preparations is a growing cause for thyrotoxicosis. However, the long-lasting effects of transient thyrotoxicosis are poorly understood. Here we examined metabolic, thermoregulatory, and cardiovascular function upon induction and recovery from a 2-week thyrotoxicosis in male C57BL/6J mice. Our results showed that T4 treatment caused tachycardia, decreased hepatic glycogen stores, and higher body temperature as expected; however, we did not observe an increase in brown fat thermogenesis or decreased tail heat loss, suggesting that these tissues do not contribute to the hyperthermia induced by thyroid hormone. Most interestingly, when the T4 treatment was ended, a pronounced bradycardia was observed in the animals, which was likely caused by a rapid decline of T3 even below baseline levels. On the molecular level, this was accompanied by an overexpression of cardiac phospholamban and Serca2a mRNA, supporting the hypothesis that the heart depends more on T3 than T4. Our findings therefore demonstrate that a transient thyrotoxicosis can have pathological effects that even persist beyond the recovery of serum T4 levels, and in particular the observed bradycardia could be of clinical relevance when treating hyperthyroid patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Body Temperature / physiology*
  • Calcium-Binding Proteins / metabolism
  • Glycogen / metabolism
  • Homeostasis / physiology
  • Liver / metabolism
  • Male
  • Mice
  • Myocardium / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • Tachycardia / etiology
  • Tachycardia / physiopathology*
  • Thermogenesis / physiology*
  • Thyrotoxicosis / chemically induced
  • Thyrotoxicosis / complications*
  • Thyroxine*


  • Calcium-Binding Proteins
  • phospholamban
  • Glycogen
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Thyroxine