This paper demonstrates the effect of the DI02 mutation on the conversion of T4 therapy to T3 and proposes appropriate treatment
DIO2 Thr92Ala Reduces Deiodinase-2 Activity andSerum-T3 Levels in Thyroid-Deficient Patients
Maria Grazia Castagna, Monica Dentice, Silvia Cantara, Raffaele Ambrosio et al
Departmentof Clinical Medicine and Surgery, University of Naples
A substantial proportion of athyreotic levothyroxine (LT4)-treated patients experiencehypothyroid-like symptoms. During LT4 replacement, levels of the active hormone triiodothyronine(T3)strictlydependontype2-deiodinase(D2)-mediatedactivationofLT4.TheThr92Alapolymorphismand the 258 G/A in the
DIO2 gene have been associated with various clinical conditions.
Objectives:
To investigate the effects of DIO2 polymorphisms in thyroid hormone homeostasis.
Design:
We compared the presurgical hormonal status of thyroidectomized LT4-treated patientswho had a similar thyroid-stimulating hormone (TSH) level with their postsurgery status andanalyzed their DIO2 genotype in a subgroup of 102/140 (72.8%) of patients. We measured the enzymatic properties of Thr92Ala in living cells and in relevant generated mouse models.
Conclusions:
Thyroidectomized patients carrying Thr92Ala are at increased risk of reduced in-tracellular and serum T3 concentrations that are not adequately compensated for by LT4, thusproviding evidence in favor of customized treatment of hypothyroidism in athyreotic patients.
J Clin Endocrinol Metab 102: 1623- 1630, 2017
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