Selenium and thyroid hormone axis in critical ill states: An overview of conflicting view points

Abstract

In critical ill states the plasma selenium levels are low and inversely correlated with the severity and outcome of the disease. The plasma selenium levels indicate the amount of circulating selenoproteins and selenoenzymes. These are important for the maintenance of the redox system, modulating the immune system and also for thyroid hormone metabolism. Not only all three deiodinases (D1-3) are selenoenzymes, but within the thyroid gland there are several other selenoenzymes, which are important for the maintenance of normal thyroid function. In critical ill states also triodothyronine (T3) is low and reverse T3 elevated, and also TSH and thyroxin (T4) are low, correlating like low plasma selenium with the severity of the disease. Subsequently, several intervention trials had been performed to evaluate whether an adjuvant selenium supplementation might attenuate the course of the disease and improve outcome. The selenium supplementation improved outcome and even reduced mortality in some but not all prospective randomized trials. A few prospective randomized intervention trials with selenium supplementation had also been performed to evaluate the hypothesis, whether low selenium is the cause of low-T3-syndrome, however, with conflicting results and no clear evidence that low D1 activity is due to the selenium deficiency in critical illness.

Because D1 catalyses the conversion of T4 to T3 and also the clearance of reverse T3, low D1 activity would sufficiently explain low plasma T3 and elevated reverse T3. It had been, however, clearly shown that cytokines are responsible for the inhibition of D1 activity, but D2 and D3 are even higher during acute inflammation in critically ill patients. One of the most important effects of selenium on the immune system seems to be the reduction of cytokine release and therefore an indirect connection between low selenium and low D1 activity has to be postulated and not a lower D1 activity due to lower availability of selenium for the D1 expression.

Introduction

In patients with acute or chronic severe non-thyroidal illness, significant changes of peripheral thyroid hormone metabolism as well as TSH occur. This so-called non-thyroidal illness syndrome (NTIS), also known as euthyroid-sick syndrome or low-T3-syndrome is characterised by altered thyroid hormones metabolism as well as lower TSH secretion. Only a few hours after the acute onset of an acute illness, T3 levels decrease. In dependence of severity and duration of the illness [1], this is followed by a fall in T4 and TSH. As the decrease in plasma T3 levels is accompanied by an increase in reverse T3, this had been explained by a decrease in the activity of D1 within the liver. The precise aetiology and the therapeutic consequences of these changes remain controversial [2]. As also the plasma selenium levels are low in patients with severe illness and sepsis [3] leading to low plasma glutathione peroxidise (GPx) activity, a decreased production and activity of the selenium-dependent D1 has been supposed leading to impaired T4 and reverse T3 metabolism. The conflicting points of this hypothesis will be reviewed.