Effect of DI02 mutation on FT3 levels in athyreotic paints on T4

[diogenes]

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

academic.oup.com/jcem/artic...

[link to full paper added by admin]

[mfinn]

Pity there isn’t customized treatment for all patients.

[dolphin5]

Very useful, thank you!!!

[Hennerton]

Thank you for this. It explains so much that was wrong after I had been on Levothyroxine only for several years and why I feel considerably better on a combination of T4/T3. Still not perfect, however but we patients get used to compensating for the thyroid loss and tend to lead our lives differently.

[Hidden in reply to Hennerton]

This mirrors my own experience.

[Hennerton in reply to Hidden]

But isn’t it shocking that they (meaning the medics) still do not understand what a fallacy is the “little white pill” which apparently, as they set about removing the thyroid, is going to be all we need for the rest of our lives? I am sure it is what you were told and I went blindly into the operation, believing every word they said. How naive I was but not any more. I question absolutely everything now.

[Mollyfan]

Thank you!

[Hidden]

Thank you for posting this Diogenes.