Non-thyroidal illness syndrome, the hidden player in the septic shock induced myocardial contractile depression

Septic shock causes high mortality in hospitalized patients, especially in those that develop myocardial dysfunction as an early complication. The myocardial dysfunction of septic shock is characterized by a decrease in ventricular relaxation (diastolic dysfunction) and reduced ventricular ejection fraction (systolic dysfunction). Most patients with septic shock have low serum thyroid hormone levels, a condition known as non-thyroidal illness syndrome. Thyroid hormones sustain myocardial contractility and energy metabolism. Septic shock non-thyroidal illness syndrome causes myocardial hypothyroidism, and hypothyroidism causes myocardial dysfunction that resembles the myocardial depression of septic shock. We hypothesize that the myocardial hypothyroidism that occurs during septic shock has a causal role in the pathogenesis of septic shock-induced myocardial dysfunction. Thyroid hormones regulate the calcium cycle, the phenotype of contractile proteins, adrenergic response, and fatty acid transport and oxidation in the cardiomyocytes. Therefore, the administration of levothyroxine and liothyronine to normalize thyroid hormones level within the myocardium will improve the myocardial function. The hypothesis will be tested in humans with septic shock by performing a prospective, randomized, placebo-controlled study to compare the effect of thyroid hormone administration with placebo on myocardial function. The proposed hypothesis challenges the idea that non-thyroidal illness syndrome is a beneficial response of the thyroid hormone axis to illness and that thyroid hormone replacement is detrimental. The administration of thyroid hormone in order to prevent and reverse myocardial hypothyroidism during septic shock is a new theoretical concept on thyroid hormone metabolism and action at the tissue level during non-thyroidal illness syndrome. If the hypothesis is correct, clinicians should consider cardiac hypothyroidism as a central player in myocardial dysfunction caused by sepsis. Thyroid hormone replacement should be incorporated into the armamentarium of septic shock treatment.