Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Experimentelle Endokrinologie, Berlin, Germany.
J Mol Endocrinol. 2021 Sep 9;67(4):161-172. doi: 10.1530/JME-21-0109.
Thyroid hormone (TH) metabolism and cellular TH action are influenced by ageing. To investigate the response to thyroxine (T4) overtreatment, a kinetic study was conducted in young and aged mice with chronic hyperthyroidism and hormone withdrawal. Five and 22 months old male mice were treated with T4 or PBS over 5 weeks, followed by observation for up to 12 days. Serial analysis was performed for thyroid function parameters, transcript levels of TH target genes, deiodinase type 1 (DIO1) activity as well as serum lipids at 12, 24, 72, 144, 216, and 288 h after cessation of T4 administration. Higher FT3 concentrations and higher renal DIO1 activities were noted in aged mice 12 h after T4 withdrawal and marked thyroid-stimulating hormone elevation was found in aged mice after 12 days compared to respective controls. A biphasic expression pattern occurred for TH target genes in all organs and a hypothyroid organ state was observed at the end of the study, despite normalization of TH serum concentrations after 72 h. In line with this, mirror-image kinetics were detected for serum cholesterol and triglycerides in aged and young mice. Recovery from TH overtreatment in mice involves short- and medium-term adaption of TH metabolism on systemic and organ levels. Increased renal DIO1 activity may contribute to higher T3 concentrations and prolonged thyrotoxicosis followed by hypothyroidism in an aged-mouse organism. Translation of these findings in the clinical setting seems warranted and may lead to better management of hyperthyroidism and prevention of T4 overtreatment in aged patients.
甲状腺激素（TH）代谢和细胞 TH 作用受年龄影响。为了研究甲状腺素（T4）过度治疗的反应，对慢性甲亢和激素撤退的年轻和老年小鼠进行了一项动力学研究。5 个月和 22 个月大的雄性小鼠接受 T4 或 PBS 治疗 5 周，然后观察长达 12 天。在停止 T4 给药后 12、24、72、144、216 和 288 小时，对甲状腺功能参数、TH 靶基因的转录水平、脱碘酶 1 型（DIO1）活性以及血清脂质进行了连续分析。在 T4 停药后 12 小时，老年小鼠的 FT3 浓度较高，肾脏 DIO1 活性较高，12 天后，与相应对照组相比，老年小鼠的促甲状腺激素明显升高。所有器官中的 TH 靶基因均呈双相表达模式，尽管 TH 血清浓度在 72 小时后恢复正常，但在研究结束时仍观察到甲状腺功能减退的器官状态。与此一致的是，老年和年轻小鼠的血清胆固醇和甘油三酯也检测到镜像动力学。从 TH 过度治疗中恢复涉及到全身和器官水平上 TH 代谢的短期和中期适应。肾脏 DIO1 活性的增加可能导致老年小鼠机体中 T3 浓度升高和甲状腺毒症持续时间延长，随后出现甲状腺功能减退。这些发现的临床转化似乎是必要的，可能会导致更好地管理甲亢和预防老年患者 T4 过度治疗。
