No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

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ineke
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Lid geworden op: 08 nov 2014, 17:53

No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

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Dubbelblind studie presentatie tijdens Internationaal Schildklier Congres met bijeenkomst van de Amerikaanse Schildklier organisatie - oktober 2015.



No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

ORLANDO, Florida — In the ongoing debate over the treatment of hypothyroidism with a combination of levothyroxine (T4) and triiodothyronine (T3), a new randomized, crossover study shows safety but no significant overall clinical benefits, using such a fixed combination.

The double-blind study, presented last week at the 2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association (ITC/ATA), involved 32 adults with primary hypothyroidism, including 30 females, who had been treated with T4 for 6 months or more.

"There is still controversy regarding whether the combination therapy is safe and effective," lead author Gilberto Paz-Filho, MD, of the Australian National University, Canberra, told Medscape Medical News.

"Our study sought to evaluate whether a unique, fixed dose of T4 plus T3 [Novothyral, Merck] could improve the well-being of patients with hypothyroidism, and while the evaluated formulation of combination therapy was safe, it was not better than T4 monotherapy [Euthyrox, Merck]."

As previously reported by Medscape Medical News, ATA guidelines issued last year recommend against the routine use of combination T4 plus T3 therapy, although they did indicate that, at the discretion of the practitioner, therapy with T3 could be attempted. This advice sparked a huge debate.

Asked to comment on the new study, session comoderator Marco Centanni, MD, of the University of Rome, Medicosurgical Sciences and Biotechnologies, Italy, said he supports the ATA guidelines on combination therapy.

"Combination T4/T3…is not a first choice in the treatment of hypothyroidism, [and this study] confirms [previously reported] negative results," he told Medscape Medical News.


Findings in Concordance with the Literature
Dr Paz-Filho reported that the patients in this new study were randomized to either continued treatment with T4 (n=17) or to start treatment with the combination of T4 and T3 (75 μg plus 15 μg per day, n=15).

After 8 weeks of treatment, the regimens were switched and treatment continued for another 8 weeks.

When researchers looked at measures of thyroid function, as well as lipid profiles, plasma glucose, body mass index (BMI) and other measures, the only significant difference at final assessments was in free T4 levels, which were significantly lower when patients were treated with combination therapy compared with T4 alone (in group one, 1.07 ng/dL at week 16 vs 1.65 ng/dL at week 8; in group two, 0.97 ng/dL at week 8 vs 1.63 ng/dL at week 16; P < .001 for both groups).


While group one also showed a significant difference in mean thyroid-stimulating-hormone (TSH) levels (P < .05), overall there were no differences in median TSH or T3 levels between the treatment regimens.

More patients showed T3 levels that were above the upper limit while on combination therapy compared with T4 alone, however (15% vs 3%).

Dr Centanni noted that a caveat of the current study was in the dosing. "The timing of treatment was insufficient," he said. "At least three administrations of T3 per day are required."


While an increase in heart rate was associated with combination-therapy use, there were no significant changes on ECG or in arterial blood pressure, and no other differences were observed in terms of body weight and quality-of-life measures such as energy, well-being, and mood complaints, Dr Paz-Filho noted.

He added, however, that more patients reported reductions in shortness of breath while on the combination therapy.

"Most of our findings are in concordance with the literature, but we were surprised to see while patients were on the combination therapy, they referred to less shortness of breath, in comparison with being on T4 monotherapy," he said. "This is an unspecific finding, with clinical significance that is unclear."


The combination therapy involved a commercially available formulation that offered some convenience and potential added measure of safety, Dr Paz-Filho added.

"This [formulation] eliminates the need for compounding the medication, which adds several confounding factors, such as dosing errors."


Still a Need for Future Studies
Explaining the rationale behind combination therapy, Dr Paz-Filho explained that patients frequently report continued symptoms of hypothyroidism after treatment with T4 alone.


"Many patients with primary hypothyroidism do not improve with the standard T4 monotherapy, despite achieving normal thyroid-hormone levels in the blood. This may occur because levothyroxine alone does not restore normal thyroid levels in tissues such as muscle and liver."

While animal studies have shown that the combination therapy can effectively restore euthyroidism in most tissues, evidence in humans has been less conclusive.

With many patients continuing to report greater improvements with combination T4 and T3 therapy, research should continue in exploring the reasons for this, Dr Paz-Filho stressed.


"In the clinics, patients empirically treated with the combination therapy refer to some improvements and prefer that type of therapy," he said.

"Therefore, there is still need for future studies with longer follow-up, evaluating the effect of long-acting, slow-release forms of T3, in patients with relatively low T3, and with polymorphisms in genes affecting thyroid economy."

Merck provided the Novothyral (T4/T3) and Euthyrox (T4) capsules used in the study. Dr Paz-Filho and Dr Centanni reported they have no relevant financial relationships.


2015 International Thyroid Congress and Annual Meeting of the American Thyroid Association; Orlando, Florida. Abstract 7, presented October 19, 2015.

http://www.medscape.com/viewarticle/853264


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laura
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Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door laura »

Eigenlijk begrijp ik niet waarom dit onderzoek gedaan is.
Niemand zit te wachten op een middel met een vaste combinatie T4+T3.

De Europese richtlijn voor T4+T3 schrijft niet zomaar: http://schildkliertje.blogspot.nl/2012/ ... 3-bij.html
Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13: 1, and are not recommended.
Waarom onderzoek doen naar iets dat al bekend is?
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.
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laura
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Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

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Met http://online.liebertpub.com/doi/pdfplu ... .abstracts vind je het abstract van Gilberto Paz-Filho.

Bekend is dat de gekozen verhouding T4/T3 niet optimaal is. Gekeken is naar gemiddelden binnen een groep en niet naar individuen. In de jaren 80 was al bekend dat door toevoeging van T3 de fT4 daalt. In 2011 schreef prof. Wiersinga over het belang onderzoek te doen naar afwijkingen in de deiodinases.

Ik vind dat zo jammer dat er weer onderzoek gedaan is naar de bekende weg.

Lees eens:
- http://schildkliertje.blogspot.nl/2015/ ... andel.html
- https://wvrtaal.files.wordpress.com/201 ... rsinga.pdf


TREATMENT OF HYPOTHYROIDISM WITH LEVOTHYROXINE PLUS TRIIODOTHYRONINE: A RANDOMIZED, DOUBLE-BLIND CROSSOVER STUDY
G.J. Paz-Filho, J. Kaminski, F.Y. Miasaki, G.A. de Carvalho

Treatment of hypothyroidism with the combination therapy levothyroxine/liothyronine (LT4/LT3) is controversial. LT4 alone may not lead to euthyroidism in some tissues, and the combination therapy may benefit select patients.

This is a randomized, double-blind, crossover study. Adults with primary hypothyroidism (n = 32, age 42.6 – 13.3, 30 females) on stable doses of LT4 for ‡ 6 months (125 or 150 mcg/day) were randomized to continue LT4 treatment (G1, n = 17), or to start LT4+ LT3 therapy (75 mcg + 15 mcg/day; G2, n = 15). After 8 weeks, participants switched treatment for 8 more weeks.

Thyroid function, lipid profile, plasma glucose, body weight, electrocardiogram (ECG), vital signs and quality of life were evaluated at baseline, and at the end of weeks 8 and 16. Baseline characteristics were similar between groups. Significant changes over the study were observed only for mean free T4 (fT4; P < .001 in both groups), and mean TSH levels (only in G1; P < .05).

In both groups, mean fT4 levels were significantly lower when patients were on LT4/LT3, when compared to while on LT4 treatment (in G1, 1.07 – 0.29 at week 16 vs. 1.65– 0.46 ng/dl at week 8; in G2, 0.97 – 0.26 at week 8 vs. 1.63 – 0.43 ng/dl at week 16). Overall, neither median TSH nor T3 levels were affected by type of therapy, in both groups.

However, more patients had T3 levels above the upper limit after being on LT4/LT3 (15%vs.3%).Moreover, the combination therapyled to an increase
in heart rate, with no significant changes in ECG and arterial blood pressure. Other parameters of lipid profile, body weight and quality of life (evaluating physical, energy/well-being, and mood/emotions complaints remained unchanged between the treatment groups.

The combination therapy LT4/LT3 in patients with hypothyroidism led to significantly lower levels of mean fT4. Neither intra nor inter-group differences in T3 levels were observed throughout the study. Despite the fact more patients on LT4/T3 had elevated T3 levels, this did not lead to significant alterations in lipid profile, arterial blood pressure, cardiac rhythm, body weight and quality of life.

No clear clinical benefit of the studied formulation LT4/LT3 could be observed in patients treated for 8 weeks. Future trials need to evaluate different formulations, and the impact of the combined therapy in select populations with deiodinase polymorphisms.
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.
ineke
Berichten: 484
Lid geworden op: 08 nov 2014, 17:53

Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door ineke »

laura schreef: Ik vind dat zo jammer dat er weer onderzoek gedaan is naar de bekende weg.
Laura,
Misschien zou jij dit kunnen navragen bij deze stichting (zie Info + link) WAAROM dit weer onderzocht is en onder de aandacht werd gebracht op het internationaal congres :!:


NB
Het staat ook op het programma voor de bijeenkomst in 2016 te Amsterdam.
11.00: T3/T4 combination therapy – evidence or just a myth?
Eric Fliers (AMC, Amsterdam)


Stichting (info _ link):
Stichting Schildklieronderzoek Nederland

Dit is de officiële site van Stichting Schildklieronderzoek Nederland, een non-profit organisatie van professionals (internist-endocrinologen en basale wetenschappers) die zich bezig houden met onderzoek naar de schildklier en schildklierhormoon in de breedste zin van het woord.

Bestuur Stichting Schildklieronderzoek Nederland
•Voorzitter: Dr. Warner Simonides, Vrije Universiteit Amsterdam
•Secretaris: Dr. Anita Boelen, Academisch Medisch Centrum, Amsterdam
•Penningmeester: Dr. Robin Peeters, Erasmus Medisch Centrum, Rotterdam
•Comité: Prof dr. Thera Links, Universitair Medisch Centrum, Groningen, Prof dr. Jan Smit, Universitair Medisch Centrum, Nijmegen

Stichting Schildklieronderzoek Nederland is geassocieerd met de Nederlands vereniging voor Endocrinologie (NVE) en de European Thyroid Association (ETA).



INVITATION
XXth annual symposium of the Dutch Thyroid Research Foundation

The Dutch Thyroid Research Foundation cordially invites you to the 20th edition of its annual symposium, which will take place on June 17 2016 at the Trippenhuis inAmsterdam. International and Dutch experts will highlight important recent developments in fundamental and clinical thyroidology. In addition, a number of young investigators have been selected for short oral presentations.

The symposium will start with a clinical session on thyroid hormone metabolism focussed on the rationale of T3/T4 combination therapy. Prof. Robin Peeters (Rotterdam) will introduce polymorphisms and genetic associations of deiodinating enzymes. Prof. Graham Williams (Imperial College) will discuss the physiology, biochemistry and possible functional impact of Dio2 polymorphisms and Prof. Eric Fliers (Amsterdam) will end the session with a discussion of T3/T4 combination therapy – evidence or just a myth? This session is followed by a basic session focussing on local thyroid hormone metabolism and action. Duncan Bassett (Imperial College, London) will present his recent findings on the role of the thyroid hormone receptor α1 and α2 in bone development followed by a presentation of Prof. Jens Mittag (Lubeck). He will present the effects of a dominant negative mutation on metabolism in a mouse model.

The focus will then shift to clinical thyroidology again with Prof. Ralf Paschke (Leipzig) addressing the molecular analysis of thyroid nodules and the promises and challenges of its application.


Zie programma
http://stichtingschildklieronderzoek.nl ... jeenkomst/



Website:
http://stichtingschildklieronderzoek.nl/



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laura
Berichten: 3600
Lid geworden op: 11 sep 2013, 22:42
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Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

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hoi Ineke,

Het gebeurt veel vaker dat iets wordt onderzocht wat eigenlijk al bekend is.
Niet alles is nieuw op zo'n congres.

Ik ben wel van plan om naar de bijeenkomst te gaan in Amsterdam.
Het zal de vijfde keer zijn dat ik ga, denk ik.
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.
ineke
Berichten: 484
Lid geworden op: 08 nov 2014, 17:53

Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door ineke »

Voor degenen die interesse hebben :

Costs including lunch and drinks:
Voor overige deelnemers: € 50,-
Aanmelden/betalen voor 17 juni a.s. > zie info onderaan



Program
9:30 Welcome and registration

10:00 Introduction
Thyroid clinical I

10.00: Polymorphisms, genetic associations and deiodinases.
Robin Peeters (Erasmus MC, Rotterdam)

10.30: Physiology, biochemistry and possible functional impact of Dio2 polymorphisms.
Graham Williams (Imperial College London, UK)

11.00: T3/T4 combination therapy – evidence or just a myth?
Eric Fliers (AMC, Amsterdam)
Thyroid hormone action and metabolism

11.30: A new model to test the involvement of cardiac deiodinase activity in heart failure
Warner Simonides (VU Medical Center, Amsterdam)

11.50: Deiodinase expression in innate immune cells
Anne van der Spek (AMC, Amsterdam)

12.10: The thyroid axis in fishes: targets for endocrine disruption
Peter Klaren (University of Nijmegen, Nijmegen)

12:30: Lunch

13.30: Novel mechanisms of Thyroid Hormone Receptor regulation.
Marcel Meima (Erasmus MC Rotterdam)

14.00: The role of TRα in metabolism
Jens Mittag (University Lubeck, Germany)

14.30: TRα1 and TRα2 expression in bone
Duncan Bassett (Imperial College London, UK)

15:00 Tea

Thyroid clinical II
15.30: Longterm effects in differentiated thyroid cancer
Esther Klein Hesselink (UMCG, Groningen)

15.50: New genes involved in central congenital hypothyroidism
Charlotte Heinen (AMC, Amsterdam)

16.10: Genetic background and mechanism of thyreostatics-induced agranulocytosis
Romana Netea (Radboud UMC, Nijmegen)

16.30 Molecular analyses of thyroid nodules, promises and challenges.
Ralf Paschke (University of Leipzig, Germany)

17:00 Drinks and farewell



REGISTRATION
By email: secr.endo.metab@amc.nl(link stuurt een e-mail) (to Anita Boelen)

Location:
Het Trippenhuis (KNAW Gebouw)
Kloveniersburgwal 29, 1011 JV Amsterdam



Organisation:
Dutch Thyroid Research Foundation (Stichting Schildklieronderzoek Nederland)
Board: dr. W.S. Simonides, dr. A. Boelen, prof. dr. R.P. Peeters, prof. dr. T.P. Links,


Costs (including lunch and drinks):
Student free
PhD students and fellows: € 25,-
Other participants: € 50,-

Please pay before 17th June, account NL02 ABNA 0469862025 t.n.v. Stichting, Schildklieronderzoek Nederland, Rotterdam




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Anoesjka
Berichten: 14
Lid geworden op: 11 jun 2015, 10:08

Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door Anoesjka »

Zaten al die mensen vóór het onderzoek ook al op dezelfde dosis? Dat zou ik graag willen weten.
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laura
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Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door laura »

hoi Anoesjka,

Als je meer wilt weten over de behandeling met T4 plus T3, dan kun je beter hier kijken: http://schildkliertje.blogspot.nl/searc ... 0plus%20T3
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.
BartP
Berichten: 2
Lid geworden op: 12 sep 2016, 02:44

Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door BartP »

Hallo,

Ben zelf eens te raden gegaan bij een Belgische endocrinoloog. Hij zij me dat T3 momenteel niet wordt voorgeschreven omdat er geen wetenschappelijke evidentie voor bestaat. Het T4 wordt uiteindelijk door de lichaamscellen omgezet naar T3 volgens de noodzaak. Hij heeft ook een website: http://drbelkhouribchia.be/index.html

Groetjes,

Bart
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laura
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Lid geworden op: 11 sep 2013, 22:42
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Re: No Thyroid-Function Benefits With T4/T3 Combo in Crossover Study

Bericht door laura »

hallo Bart,

In Nederland kan het wel voorgeschreven worden.
Of T3 dát wondermiddel is? Dat denk ik niet.
Wel is er ruimte om het te proberen.
En daar is, vind ik, veel voor te zeggen.

Lees dit eens: http://schildkliertje.blogspot.nl/2012/ ... tomel.html
laura

Kijk voor meer informatie ook eens op Schildkliertje.

Raadpleeg altijd een arts als je twijfelt over je gezondheid.
Het Schildklierforum kan niet worden beschouwd als vervanging van een consult of een behandeling.
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