Fliers E, Guldenaar S E, Wiersinga W M, Swaab D F
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, The Netherlands.
J Clin Endocrinol Metab. 1997 Dec;82(12):4032-6. doi: 10.1210/jcem.82.12.4404.
Changes in hypothalamus-pituitary-thyroid function occur in patients with a variety of illnesses and are referred to as the euthyroid sick syndrome or nonthyroidal illness (NTI). In NTI, serum concentrations of T3 decrease to low, or even undetectable, levels without giving rise to elevated concentrations of TSH. We hypothesized that decreased activity of TRH-producing cells in the paraventricular nucleus (PVN) contributes to the persistence of low TSH levels. To test this hypothesis, we collected a series of formalin-fixed, paraffin-embedded hypothalami of patients whose plasma concentrations of T3, T4, and TSH had been measured in a blood sample taken less than 24 h before death. Quantitative TRH messenger RNA in situ hybridization (intraassay coefficient of variation: 13%) was performed in the PVN. Total TRH messenger RNA in the PVN showed a positive correlation with serum T3 (r = 0.66; P < 0.05) and with logTSH (r = 0.64; P < 0.05), but not with T4 (r = -0.02; P = 0.95). This is the first study to correlate premortem serum concentrations of thyroid hormones with postmortem gene expression of identified neurons in the human hypothalamus. The results suggest an important role for TRH cells in the pathogenesis of NTI.
下丘脑 - 垂体 - 甲状腺功能变化发生在患有各种疾病的患者中，被称为甲状腺功能正常的病态综合征或非甲状腺疾病（NTI）。在NTI中，血清T3浓度降至低水平甚至无法检测到，而不会导致TSH浓度升高。我们假设室旁核（PVN）中产生促甲状腺激素释放激素（TRH）的细胞活性降低导致TSH水平持续偏低。为了验证这一假设，我们收集了一系列福尔马林固定、石蜡包埋的下丘脑样本，这些患者在死亡前不到24小时采集的血样中已检测了血浆T3、T4和TSH浓度。在PVN中进行了TRH信使核糖核酸（mRNA）的定量原位杂交（批内变异系数：13%）。PVN中的总TRH mRNA与血清T3呈正相关（r = 0.66；P < 0.05），与logTSH呈正相关（r = 0.64；P < 0.05），但与T4无相关性（r = -0.02；P = 0.95）。这是第一项将人类下丘脑死后特定神经元的基因表达与死前甲状腺激素血清浓度相关联的研究。结果表明TRH细胞在NTI发病机制中起重要作用。
