[SPINA] Large study unveils existence of a TSH-T3 shunt in vivo.

[Johannes W. Dietrich]

Results of a large clinical observation study suggest that thyroid  
homeostasis might be more complex than previously assumed. Combining  
data of more than 1000 patients with results of computer simulations  
delivered new hints that in humans TSH might stimulate deiodinase  
activity in vivo.

For a long time it was known that cAMP up-regulates both type 1 and  
type 2 deiodinase, and it could also be shown that TSH (which  
stimulates intracellular cAMP release) is able to increase  
deiodination on both transcriptional and post-translational levels.  
However, these observations resulted from animal experiments and cell  
culture investigations only, and it was unknown if they are of  
relevance in humans in vivo.

Calculating SPINA-GD in a large cohort of patients, a part of them  
receiving substitution therapy with levothyroxine (L-T4), showed now  
that deiodinase activity positively correlates with TSH  
concentrations, but only in patients with residual thyroid function.  
Consistently with this latter observation, SPINA-GD correlated with  
the amount of residual thyroid tissue, and it significantly decreased  
after thyroidectomy.

Comparing in vivo data with results of sensitivity analysis with  
SimThyr showed that in vivo FT3 levels remained constant over a broad  
range of thyroid's secretory capacity (GT) or supply with L-T4, while  
it correlated positively with T4 output in computer simulations that  
didn't account for the TSH-T3 shunt. Correlation between L-T4 supply  
and FT3 levels was also seen, however, in a subgroup of patients with  
thyroid carcinoma who had received thyroidectomy and remnant ablation  
with high-dose radioiodine.

The results of this study suggest that a TSH-T3 shunt is existent and  
active in humans in vivo, that is is mediated by functional thyroid  
tissue and that it compensates for abating thyroid function in  
beginning hypothyroidism.

Future investigations with this methodology might help to identify a  
subgroup of patients who benefit from combination therapy with L-T4  
and L-T3.


References

1: Hoermann R, Midgley JE, Giacobino A, Eckl WA, Wahl HG, Dietrich JW,  
Larisch R. Homeostatic equilibria between free thyroid hormones and  
pituitary thyrotropin are modulated by various influences including  
age, body mass index and treatment. Clin Endocrinol (Oxf). 2014 Dec; 
81(6):907-15. doi: 10.1111/cen.12527. PMID 24953754.

2: Hoermann R, Midgley JE, Larisch R, Dietrich JW. Integration of  
Peripheral and Glandular Regulation of Triiodothyronine Production by  
Thyrotropin in Untreated and Thyroxine-Treated Subjects. Horm Metab  
Res. 2015 Mar 6. [Epub ahead of print] PMID 25750078.



-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --  
-- --
-- Dr. med. Johannes W. Dietrich
-- Oberarzt / Consultant Endocrinologist
-- Laboratory XU44, Endocrine Research
-- Medical Hospital I, Bergmannsheil University Hospitals
-- Ruhr University of Bochum
-- Buerkle-de-la-Camp-Platz 1, D-44789 Bochum, NRW, Germany
-- Phone: +49:234:302-6400, Fax: +49:234:302-6403
-- eMail: "j.w.dietrich at medical-cybernetics.de"
-- WWW: http://www.thyreologie.com.de
-- WWW: http://www.uk.rub.de
-- Researcher ID: C-3498-2009
-- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- -- --  
-- --





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