Koehler Viktoria Florentine, Knösel Thomas, Hasmann Sandra Elisabeth, Scherer Clemens, Hellmuth Johannes C, Muenchhoff Maximilian, Munker Stefan Micheal, Hoster Eva, Ladurner Roland, Spitzweg Christine
Department of Internal Medicine IV, LMU Munich, Germany.
Department of Medicine I, Goethe University Hospital, Frankfurt, Germany.
Thyroid. 2023 Feb;33(2):177-185. doi: 10.1089/thy.2022.0229.
Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is owing to fatal inflammatory responses apart from lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to nonthyroidal illness syndrome have been described. Furthermore, angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients who died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFTs with the severity of the disease in a prospective cohort study. Thyroid tissue of deceased COVID-19 patients ( = 23) was analyzed for histopathology and ACE2 expression by immunohistochemical staining. A total of 153 patients with confirmed SARS-CoV-2 were evaluated regarding TFTs and divided into a severe (intubation, intensive care treatment) and an intermediate group. Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and thyrotropin (TSH) was associated significantly with deadly disease. The high percentage of positive ACE2 immunostaining in deceased patients compared with normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L were associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFTs is crucial in the treatment of severely ill COVID-19 patients. COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.
感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）最初被认为是一种呼吸道疾病，但在疫情过程中，人们逐渐认识到，除了肺部损伤外，病情严重是由于致命的炎症反应。在这种情况下，除了非甲状腺疾病综合征外，还描述了甲状腺炎等内分泌紊乱以及垂体功能障碍。此外，在包括甲状腺在内的大多数内分泌组织中都检测到了SARS-CoV-2细胞受体血管紧张素转换酶2（ACE2）。在一项回顾性病例系列研究中，评估死于重症冠状病毒病2019（COVID-19）的患者甲状腺组织的组织病理学变化，并比较其与未感染SARS-CoV-2患者甲状腺组织中甲状腺ACE2蛋白表达情况。此外，在前瞻性队列研究中，评估并比较感染或未感染SARS-CoV-2患者的甲状腺功能检查（TFT）变化，以及TFT与疾病严重程度的关联。通过免疫组织化学染色分析了23例死亡COVID-19患者的甲状腺组织的组织病理学和ACE2表达情况。对153例确诊SARS-CoV-2感染的患者进行了TFT评估，并将其分为重症组（插管、重症监护治疗）和中度组。在87%的死亡COVID-19患者中检测到甲状腺ACE2表达。未感染SARS-CoV-2患者的正常甲状腺组织未显示ACE2蛋白表达。一半的重症COVID-19患者游离三碘甲状腺原氨酸（fT3）水平较低。低fT3和促甲状腺激素（TSH）的组合与致命疾病显著相关。与未感染SARS-CoV-2患者的正常甲状腺组织相比，死亡患者中ACE2免疫染色阳性率较高，这表明甲状腺参与了COVID-19，尽管进一步的研究将不得不揭示甲状腺ACE2在COVID-19中的致病作用。在我们的重症SARS-CoV-2患者队列中，异常fT3和TSH≤0.5 mU/L与致命结局相关。因此，评估TFT对重症COVID-19患者的治疗至关重要。慕尼黑大学医院COVID-19注册研究（CORKUM），世界卫生组织试验编号DRKS00021225。
