Scope and limitations of iodothyronine deiodinases in hypothyroidism

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dc.contributor.authorGereben B.
dc.contributor.authorMcAninch E.A.
dc.contributor.authorRibeiro M.O.
dc.contributor.authorBianco A.C.
dc.date.accessioned2024-03-13T00:55:59Z
dc.date.available2024-03-13T00:55:59Z
dc.date.issued2015
dc.description.abstract© 2015 Macmillan Publishers Limited. All rights reserved.The coordinated expression and activity of the iodothyronine deiodinases regulate thyroid hormone levels in hypothyroidism. Once heralded as the pathway underpinning adequate thyroid-hormone replacement therapy with levothyroxine, the role of these enzymes has come into question as they have been implicated in both an inability to normalize serum levels of tri-iodothyronine (T 3) and the incomplete resolution of hypothyroid symptoms. These observations, some of which were validated in animal models of levothyroxine monotherapy, challenge the paradigm that tissue levels of T 3 and thyroid-hormone signalling can be fully restored by administration of levothyroxine alone. The low serum levels of T 3 observed among patients receiving levothyroxine monotherapy occur as a consequence of type 2 iodothyronine deiodinase (DIO2) in the hypothalamus being fairly insensitive to ubiquitination. In addition, residual symptoms of hypothyroidism have been linked to a prevalent polymorphism in the DIO2 gene that might be a risk factor for neurodegenerative disease. Here, we discuss how these novel findings underscore the clinical importance of iodothyronine deiodinases in hypothyroidism and how an improved understanding of these enzymes might translate to therapeutic advances in the care of millions of patients with this condition.
dc.description.firstpage642
dc.description.issuenumber11
dc.description.lastpage652
dc.description.volume11
dc.identifier.doi10.1038/nrendo.2015.155
dc.identifier.issn1759-5037
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/36130
dc.relation.ispartofNature Reviews Endocrinology
dc.rightsAcesso Restrito
dc.titleScope and limitations of iodothyronine deiodinases in hypothyroidism
dc.typeArtigo de revisão
local.scopus.citations99
local.scopus.eid2-s2.0-84945440446
local.scopus.subjectAnimals
local.scopus.subjectBrain Diseases
local.scopus.subjectHumans
local.scopus.subjectHypothyroidism
local.scopus.subjectIodide Peroxidase
local.scopus.subjectThyroid Hormones
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84945440446&origin=inward
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