Lado-Abeal Joaquin
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Truman Medical Centers and University of Missouri Kansas City, MO, USA.
Med Hypotheses. 2020 Sep;142:109775. doi: 10.1016/j.mehy.2020.109775. Epub 2020 Apr 22.
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.
脓毒性休克在住院患者中导致高死亡率，尤其是那些早期并发心肌功能障碍的患者。脓毒性休克的心肌功能障碍的特征是心室舒张功能下降（舒张功能障碍）和心室射血分数降低（收缩功能障碍）。大多数脓毒性休克患者血清甲状腺激素水平较低，这种情况称为非甲状腺疾病综合征。甲状腺激素维持心肌收缩力和能量代谢。脓毒性休克非甲状腺疾病综合征导致心肌甲状腺功能减退，而甲状腺功能减退导致的心肌功能障碍类似于脓毒性休克时的心肌抑制。我们假设脓毒性休克期间发生的心肌甲状腺功能减退在脓毒性休克诱导的心肌功能障碍的发病机制中起因果作用。甲状腺激素调节心肌细胞中的钙循环、收缩蛋白表型、肾上腺素能反应以及脂肪酸转运和氧化。因此，给予左甲状腺素和碘塞罗宁以使心肌内甲状腺激素水平正常化将改善心肌功能。将通过进行一项前瞻性、随机、安慰剂对照研究来比较给予甲状腺激素与安慰剂对心肌功能的影响，从而在脓毒性休克患者中检验该假设。所提出的假设挑战了非甲状腺疾病综合征是甲状腺激素轴对疾病的有益反应且甲状腺激素替代有害的观点。在脓毒性休克期间给予甲状腺激素以预防和逆转心肌甲状腺功能减退是关于非甲状腺疾病综合征期间甲状腺激素代谢和组织水平作用的一个新的理论概念。如果该假设正确，临床医生应将心脏甲状腺功能减退视为脓毒症所致心肌功能障碍的核心因素。甲状腺激素替代应纳入脓毒性休克治疗手段之中。
