Hypothyroidism Clinical Trial
Official title:
Effect of Restoration of Euthyroidism in Patients With Primary Hypothyroidism on Brown Adipose Tissue Thermogenesis - the ThyroBAT Study
The investigators aim to study whether hypothyroidism negatively affects Brown adipose tissue (BAT) function in humans and whether BAT function can be restored to normal by thyroid hormone supplementation.
Hypothyroidism is a frequent endocrine disorder, the prevalence of subclinical disease being
4.3% and of overt disease being 0.3%. Patients suffering from hypothyroidism frequently
complain of increased cold sensitivity and involuntary weight gain, indicating changes in
energy expenditure and response to cold challenge.
Recently, brown adipose tissue (BAT) has regained attention as an energy expending tissue.
While it was previously thought to be of no or negligible relevance in human adults, recent
studies clearly demonstrated the presence and metabolic activity of BAT in human adults. Upon
activation of BAT by the sympathetic nervous system intracellular lipid stores are rapidly
depleted. The generated free fatty acids fuel beta-oxidation and the respiratory chain within
the mitochondria and activate at the same time uncoupling protein 1 (UCP1). This protein acts
as a protonophore, allowing the flux of protons along the electrochemical gradient into the
inner mitochondrial matrix instead of transferring their energy to adenosine triphosphate
(ATP)-synthase. The short circuiting of the oxidative phosphorylation within the mitochondria
leads to highly active cellular respiration and generation of heat. Basic research highlights
the importance of thyroid hormone in the development and function of BAT.
It has recently been shown that hyperthyroidism exerts activating effects on BAT in adult
humans.
The investigators aim to study whether hypothyroidism negatively affects BAT function in
humans and whether BAT function can be restored to normal by thyroid hormone supplementation.
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