Thyroid Disorders in Patients Treated with Dimethyl Fumarate for Multiple Sclerosis: A Retrospective Observational Study.
Graves’ disease
Keap1
Nrf2
dimethyl fumarate
goiter
thyroid
Journal
Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981
Informations de publication
Date de publication:
21 May 2022
21 May 2022
Historique:
received:
01
03
2022
revised:
09
05
2022
accepted:
17
05
2022
entrez:
28
5
2022
pubmed:
29
5
2022
medline:
29
5
2022
Statut:
epublish
Résumé
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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
In a retrospective observational study, we investigated the prevalence and incidence of thyroid disorders (TD) among 163 patients with MS treated with DMF.
RESULTS
RESULTS
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.
CONCLUSIONS
CONCLUSIONS
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.
Identifiants
pubmed: 35624879
pii: antiox11051015
doi: 10.3390/antiox11051015
pmc: PMC9138003
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Swiss National Science Foundation
ID : 323530_199386
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 310030_192738
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 31003A_182105
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : IZCOZ0_177070
Pays : Switzerland
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