Renaud Cédric O, Ziros Panos G, Mathias Amandine, Pot Caroline, Sykiotis Gerasimos P
Service of Endocrinology, Diabetology and Metabolism, Lausanne University Hospital and University of Lausanne, CH-1011 Lausanne, Switzerland.
Laboratories of Neuroimmunology, Neuroscience Research Center and Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, CH-1011 Lausanne, Switzerland.
Antioxidants (Basel). 2022 May 21;11(5):1015. doi: 10.3390/antiox11051015.
Dimethyl fumarate (DMF), a drug used for the treatment of multiple sclerosis (MS) and psoriasis, has been shown to activate the Keap1/Nrf2 antioxidant response. Nrf2 exerts pleiotropic roles in the thyroid gland; among others, single nucleotide polymorphisms (SNPs) in the gene encoding Nrf2 modulate the risk of Hashimoto's thyroiditis (HT), suggesting that pharmacological activation of Nrf2 might also be protective. However, a patient with acute exacerbation of HT after starting DMF for MS was recently reported, raising questions about the thyroidal safety of Nrf2 activators.
In a retrospective observational study, we investigated the prevalence and incidence of thyroid disorders (TD) among 163 patients with MS treated with DMF.
Only 7/163 patients (4.3%) were diagnosed with functional TD; most (5/163, 3.0%) were diagnosed before DMF treatment. Functional TD were diagnosed under or after DMF in only 2 patients (1.2%). Under DMF, one patient developed transient mild hypothyroidism with negative thyroid autoantibodies. After DMF discontinuation, another patient developed hyperthyroidism due to Graves' disease. No patient developed thyroid structural disease under or after DMF.
The very low incidence of functional TD indicates an overall very good thyroid tolerance of DMF, arguing against screening for TD in MS patients considered for or treated with DMF, and supporting the further study of Nrf2 activators for the prevention and treatment of TD.
富马酸二甲酯（DMF）是一种用于治疗多发性硬化症（MS）和银屑病的药物，已被证明可激活Keap1/Nrf2抗氧化反应。Nrf2在甲状腺中发挥多效性作用；其中，编码Nrf2的基因中的单核苷酸多态性（SNP）调节桥本甲状腺炎（HT）的风险，这表明Nrf2的药理学激活可能也具有保护作用。然而，最近有报道称一名MS患者在开始使用DMF治疗后出现HT急性加重，这引发了关于Nrf2激活剂甲状腺安全性的问题。
在一项回顾性观察研究中，我们调查了163例接受DMF治疗的MS患者中甲状腺疾病（TD）的患病率和发病率。
仅7/163例患者（4.3%）被诊断为功能性TD；大多数（5/163，3.0%）在DMF治疗前被诊断。仅2例患者（1.2%）在DMF治疗期间或之后被诊断为功能性TD。在DMF治疗期间，1例患者出现短暂性轻度甲状腺功能减退，甲状腺自身抗体阴性。停用DMF后，另1例患者因格雷夫斯病出现甲状腺功能亢进。在DMF治疗期间或之后，没有患者出现甲状腺结构性疾病。
功能性TD的发病率极低，表明DMF对甲状腺的总体耐受性非常好，则不主张对考虑使用或正在接受DMF治疗的MS患者进行TD筛查，并支持进一步研究Nrf2激活剂用于预防和治疗TD。
