Thyroid hormone metabolism during inflammation and fasting

Pathophysiological circumstances such as illness and fasting affect the hypothalamus-pituitary-thyroid (HPT)-axis. The illness induced alterations, collectively known as the non-thyroidal illness syndrome (NTIS) are characterized by decreased serum T3 and T4 concentrations, increased serum rT3 concentrations and unaltered or inappropriately low serum TSH, indicating profoundly altered negative feedback in the pituitary and hypothalamus. Similar changes are observed during fasting. We recently showed that besides alterations in serum thyroid hormone (TH) concentrations, both illness and fasting are accompanied by tissue specific changes in deiodinases, which determine the availability of thyroid hormone (TH) in tissues. In this thesis we describe the experiments we have performed to investigate the underlying mechanisms of local changes in deiodinase activity; type 2 deiodinase activity in the hypothalamus during inflammation and type 3 deiodinase activity in the liver and white adipose tissue during fasting.