Studies of Thyroid Function in Health and Disease

自身免疫性甲状腺疾病如Graves病可能与甲状腺外表现有关——眼窝病、皮肤病和肢端肿（骨膜改变和手指和脚趾的杵状变）。严重形式的格雷夫斯皮肤病，如结节性皮肤病或疣状外象皮病，可引起显著的发病率。格雷夫斯皮肤病的病理生理机制尚不清楚。多种因素的结合可能促进其发展，包括免疫因素，如T淋巴细胞和B淋巴细胞的浸润，细胞因子的产生，血清促甲状腺激素受体抗体（TRAbs）与真皮组织中促甲状腺激素和胰岛素样生长因子I受体之间的相互作用；细胞因子，如成纤维细胞产生的糖胺聚糖；其他因素，如吸烟、局部创伤、依赖性水肿等。许多药物已被用于治疗这种疾病，包括糖皮质激素、沙利度胺、环磷酰胺、静脉注射免疫球蛋白、英夫利昔单抗、己酮茶碱、利妥昔单抗和利妥昔单抗加血浆置换，但所有药物均产生有限和可变的反应。联合免疫抑制治疗Graves皮肤病的疗效尚不清楚。

Autoimmune thyroid disorders such as Graves disease might be associated with extrathyroidal manifestations - orbitopathy, dermopathy, and acropachy (periosteal changes and clubbing of fingers and toes). Severe forms of Graves dermopathy, such as nodular dermopathy or elephantiasis nostras verrucosa, can cause significant morbidity. The pathophysiology of Graves dermopathy is poorly understood. A combination of factors may contribute to its development, including immunologic factors, such as infiltration of T and B lymphocytes, cytokine production, interactions between serum thyroid-stimulating hormone receptor antibodies (TRAbs) and thyroid-stimulating hormone and insulin-like growth factor I receptors in dermal tissues; cellular factors, such as glycosaminoglycan production from fibroblasts; and other factors, such as smoking, local trauma, and dependent edema. Many agents have been used to treat this condition, including monotherapy with glucocorticoids, thalidomide, cyclophosphamide, intravenous immunoglobulins, infliximab, pentoxifylline, rituximab, and rituximab plus plasmapheresis, but all have produced limited and variable responses. The efficacy of combined immunosuppressive therapy for Graves dermopathy is unknown. We have successfully used combined immunosuppressive therapy to treat a patient with severe, refractory Graves dermopathy. Case Report: We provided care for a 55-year-old man with severe, disabling dermopathy, acropachy, and elephantiasis that developed gradually over 20 years. We started combined immunosuppressive therapy with a single course of rituximab, dexamethasone, and oral cyclophosphamide At 12 months, the physical examination found resolution of Graves dermopathy of the upper extremities and marked improvement in the appearance and function of the lower extremities, including the ability of the patient to wear shoes. An MRI scan documented a substantial reduction in soft tissue swelling of the patient's extremities. His quality-of-life score, as measured by the Short Form-36 questionnaire, increased from 425.8 to 582.5 points (maximum achievable score, 800; mean score in the general population, 584). Serum autoantibodies levels (TRABs) decreased from greater than 40 to 1.12 IU/L (normal, 0 to 1.75 IU/L), as documented by immunoassay and by the luciferase immunoprecipitation system assay. Combined immunosuppressive therapy appears to be a safe and effective option for the management of severe Graves dermopathy. We also performed a pilot study, using mass spectrometry analysis of steroid and thyroid hormone profiles in patients hospitalized with SARS-CoV-2 at two tertiary referral centers. Liquid chromatography mass spectrometry analysis of adrenocortical steroids progesterone, corticosterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione, testosterone, total thyroxine (TT4), total triiodothyronine (TT3), reverse triiodothyronine (rT3), and immunoassay analysis of adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), luteinizing and follicle-stimulating hormones, and aldosterone were performed. We found about 17.7% of TSH values being low, up to 52.8% of TT4 and 69.4% of TT3 values being low, while 52.8% of rT3 values were elevated. This biochemical pattern of low TT4 and TT3, elevated rT3, and low to normal TSH is suggestive of non-thyroidal systemic illness syndrome commonly associated with COVID19.