Thyroid Disorders in Patients Treated with Dimethyl Fumarate for Multiple Sclerosis: A Retrospective Observational Study

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...

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Bibliographic Details
Published in:Antioxidants 2022-05, Vol.11 (5), p.1015
Main Authors: Renaud, Cédric O, Ziros, Panos G, Mathias, Amandine, Pot, Caroline, Sykiotis, Gerasimos P
Format: Article
Language:English
Subjects:
Antioxidants
Autoantibodies
dimethyl fumarate
goiter
Graves' disease
Hyperthyroidism
Hypothyroidism
Immunology
Keap1
Medical records
Multiple sclerosis
Nrf2
NRF2 protein
Observational studies
Patients
Psoriasis
Single-nucleotide polymorphism
Thyroid
Thyroid diseases
Thyroid gland
Thyroiditis
Transcription factors
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Summary: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.
ISSN:2076-3921
2076-3921
DOI:10.3390/antiox11051015