The hypothalamus-pituitary-thyroid axis in critical illness.
The thyroid axis is comprised of thyrotropin-releasing hormone (TRH) at the level of the hypothalamus which stimulates the pituitary to release thyrotropin (TSH). TSH in turn stimulates the thyroid to secrete the pro-hormone thyroxin (T4) and to a lesser extent the receptor active hormone tri-iodothyronine (T3). The majority of circulating T3 is generated by peripheral conversion of T4 by the intracellular iodothyronine deiodinases. Thyroid hormone (TH) is transported over the cell membrane by specific TH transporters such as monocarboxylate transporter 8 (MCT8). After transport and metabolisation in the cell, T3 can interact with nuclear TH receptors and activate or inactivate TH responsive genes. Critically ill patients show uniform disturbances in the hypothalamus-pituitary-thyroid axis. There is clear evidence that circulating and tissue TH levels are low and this is called the low T3 syndrome or non-thyroidal illness syndrome. The clinical importance of the low T3 syndrome is still not very clear because it can either protect against or aggravate the catabolic state. Recently, novel insights were generated into the pathophysiology of the low T3 syndrome. Recent studies in animal models as well as in patients have shown alterations in TH transport and also in deiodinase activity which, together, may suggest an attempt of certain peripheral tissues as well as of the hypothalamus to compensate for low circulating TH levels. Reduced expression of TRH in the hypothalamus appears to play a key role in the prolonged phase of critical illness, although the processes that trigger this upstream disturbance remain unclear.
Mebis
L
L
Department of Intensive Care, Katholieke Universiteit Leuven, Belgium.
van den Berghe
G
G
D000818:Animals; D016638:Critical Illness; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology* / Q000503:physiopathology; D007453:Iodide Peroxidase / Q000378:metabolism; D013961:Thyroid Gland / Q000502:physiology* / Q000503:physiopathology; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D016207:Cytokines; D013963:Thyroid Hormones; D014284:Triiodothyronine; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine