Michalaki M, Vagenakis A G, Makri M, Kalfarentzos F, Kyriazopoulou V
Department of Medicine, University of Patras Medical School, University Hospital, Patras 26500, Greece.
J Clin Endocrinol Metab. 2001 Sep;86(9):4198-205. doi: 10.1210/jcem.86.9.7795.
The etiology of the prompt decline in serum T(3) in patients with nonthyroidal illness syndrome has not been adequately explained. It has been attributed to various parameters, including test artifacts, inhibitors of T(4) and T(3) binding to proteins, decreased 5'-deiodinase activity, and circulating cytokines. Currently, much attention is centered on the role of IL-6 and TNFalpha in developing the nonthyroidal illness syndrome through an effect on the hypothalamus, pituitary, and possibly 5'-deiodinase activity. We therefore studied the relation of the endogenous serum IL-6 and TNFalpha rise early in the course of nonthyroidal illness syndrome to the early decline in serum T(3) in 19 apparently healthy individuals, aged 43 +/- 16 yr, who underwent elective abdominal surgery for cholelithiasis or gastroplasty. Serum T(3), free T(3), T(4), free T(4), rT(3), TSH, IL-6, and TNFalpha were measured before and at various time intervals up to 42 h after skin incision. We observed a prompt decline in serum T(3) 30 min before skin incision, which continued to decline throughout the observational period. The magnitude of the decline reached 20% from the baseline value at 2 h. The early decline of T(3) was attenuated and lasted from the 2-8 h, probably due to the sharp increase in serum TSH that started immediately after the entrance to the operating room and lasted for 2 h. In contrast, serum T(4) and free T(4) concentrations were increased soon after skin incision and remained elevated during the first postoperative day. Serum rT(3) increased approximately 6 h after the initiation of surgery and remained elevated thereafter. Serum IL-6 remained essentially undetectable for 2 h after skin incision, whereas serum T(3) was low. Two hours after skin incision, serum IL-6 increased sharply and remained elevated throughout the observational period. Serum TNFalpha remained essentially undetectable throughout the postoperative period. Serum cortisol increased rapidly upon entrance to the operating room and remained elevated throughout the postoperative period. We conclude that the decline in serum T(3) early in the course of nonthyroidal illness syndrome is not due to increased serum IL-6 or TNFalpha levels. The brisk TSH secretion soon after the onset of the syndrome attenuates the decline in serum T(3) due to T(3) secretion from the thyroid. The early and brisk cortisol response to surgery may at least in part explain the early decrease in serum T(3) in nonthyroidal illness syndrome.
非甲状腺疾病综合征患者血清T(3)迅速下降的病因尚未得到充分解释。其原因被归结为多种因素，包括检测假象、T(4)和T(3)与蛋白质结合的抑制剂、5'-脱碘酶活性降低以及循环细胞因子。目前，人们的注意力主要集中在IL-6和TNFα通过对下丘脑、垂体以及可能对5'-脱碘酶活性的影响在非甲状腺疾病综合征发生过程中所起的作用。因此，我们研究了19名年龄为43±16岁、因胆结石或胃成形术接受择期腹部手术的表面健康个体在非甲状腺疾病综合征病程早期内源性血清IL-6和TNFα升高与血清T(3)早期下降之间的关系。在皮肤切开前及切开后长达42小时的不同时间间隔测量血清T(3)、游离T(3)、T(4)、游离T(4)、反T(3)、TSH、IL-6和TNFα。我们观察到在皮肤切开前30分钟血清T(3)迅速下降，并在整个观察期持续下降。下降幅度在2小时时达到基线值的20%。T(3)的早期下降在2至8小时时减弱并持续，这可能是由于进入手术室后立即开始并持续2小时的血清TSH急剧升高所致。相比之下，皮肤切开后不久血清T(4)和游离T(4)浓度升高，并在术后第一天保持升高。血清反T(3)在手术开始后约6小时升高，并此后一直保持升高。皮肤切开后2小时内血清IL-6基本检测不到，而此时血清T(3)较低。皮肤切开后2小时，血清IL-6急剧升高，并在整个观察期保持升高。血清TNFα在术后整个期间基本检测不到。进入手术室后血清皮质醇迅速升高，并在术后整个期间保持升高。我们得出结论，非甲状腺疾病综合征病程早期血清T(3)的下降并非由于血清IL-6或TNFα水平升高。综合征发作后不久迅速分泌的TSH减弱了由于甲状腺分泌T(3)导致的血清T(3)下降。手术早期迅速出现的皮质醇反应可能至少部分解释了非甲状腺疾病综合征中血清T(3)的早期降低。
