Nieuwe ATA-richtlijn: alleen T4 bij hypothyreoïdie

[ineke]

New ATA Guidelines stick with levothyroxine for hypothyroidism

Levothyroxine as monotherapy should remain the standard of care for the treatment of hypothyroidism, despite the common combination of the drug with alternative agents to tackle tough cases of the condition, according to new treatment guidelines set forth by the American Thyroid Association (ATA). "All in all, our guidelines offer reassurance to physicians and their patients [that] no changes are needed in the current standard of care for hypothyroidism in the majority of patients," said Jacqueline Jonklaas, MD, PhD, chair of the task force looking into the issue and an associate professor at Georgetown University Medical Center, in Washington, DC, in a press statement.

Levothyroxine, sold as Synthroid (AbbVie) and other trade names as well as generics, is well established as the gold standard of treatment for hypothyroidism; however, alternative therapies have emerged for the relatively few patients — about 15% — who don't respond well to the drug, necessitating this updated look at treatment strategies, Dr. Jonklaas told Medscape Medical News. "More studies have been conducted on combination therapy with [the thyroid hormone triiodothyronine] T3 in recent years, and so the American Thyroid Association thought it would be wise to rereview the evidence," she said.

Time to Rereview the Evidence
Levothyroxine is a synthetic form of the hormone T4 that is converted to T3 inside the body. Dr. Jonklaas and the expert task force explain in their paper, published online September 29 in Thyroid, that some patients feel unwell while taking levothyroxine monotherapy. While the number of such patients does not appear to be increasing, "it does concern physicians that there are any patients at all who do not feel returned to full health," she explained.

The task force was therefore convened to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with this therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. "We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care," they explain in the paper. They conducted an extensive literature review of 3 commonly used therapeutic categories: levothyroxine monotherapy; non–levothyroxine-based thyroid-hormone therapies including nutraceuticals, thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones; and the use of thyroid-hormone analogs.

The challenges of titrating thyroid-hormone therapy in specific groups such as the pediatric, pregnant, and elderly populations are also discussed, but the topic of subclinical hypothyroidism is not addressed, other than in the pediatric population, "because of prior extensive reviews of this topic in adults," say the task force. They found that, overall, the evidence was insufficient to justify a change in the treatment guidelines. "The studies were performed in many different ways [and] had some inconsistent findings, and none looked at use of a T3 agent for an extended period, which is necessary to uncover side effects," Dr. Jonklaas explained.

While some studies suggested combination therapy could be a valid approach, the expert panel concluded there was not yet robust evidence to recommend this. "More studies need to be done before we could really be sure of this result," Dr. Jonklaas urged. Nevertheless, she said the door is left open for certain patients who may indeed benefit from combination therapies for hypothyroidism. "It is possible that patients with a certain genetic makeup — a polymorphism or genetic variation in the deiodinase enzyme that converts levothyroxine (T4 to T3) — may specifically benefit from combination therapy," she noted. "We should…conduct studies that specifically examine treatment in the individuals who have the genetic characteristic that was identified in the preliminary studies," she said.

Essential Guidance for Endocrinologists
"Despite the advances that have occurred in the field of therapy for hypothyroidism, there are still many unanswered questions," the task force concludes. Nevertheless, the new guidelines will provide essential guidance to clinicians, Hossein Gharib, MD, president of the ATA, professor of medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, said in a press statement. "These ATA guidelines, developed by an expert team, provide useful, up-to-date information on why to treat, who to treat, and how to treat hypothyroidism. "Information is evidence-based and recommendations are graded. I think they will be used extensively by all clinical endocrinologists, especially by our members," he concluded.

Dr. Jonklaas reports that she and a coinvestigator, Kenneth D Burman, MD, director of the endocrine section at MedStar Washington Hospital Center in Washington, DC, have conducted a study of a T3 product funded by IPE; however the study was designed only to look at blood levels of T3, and the product was not discussed in the guidelines. The other coauthors have reported no relevant financial relationships.

Bronnen:
Bovenstaand artikel: http://www.medscape.com/viewarticle/832682

ATA richtlijnen: GUIDELINES FOR THE TREATMENT OF HYPOTHYROIDISM
Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement
http://online.liebertpub.com/doi/pdfplu ... .2014.0028


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[laura]

New ATA Guidelines stick with levothyroxine for hypothyroidism

Dr. Jonklaas reports that she and a coinvestigator, Kenneth D Burman, MD, director of the endocrine section at MedStar Washington Hospital Center in Washington, DC, have conducted a study of a T3 product funded by IPE; however the study was designed only to look at blood levels of T3, and the product was not discussed in the guidelines.

Voor dat onderzoek naar slow-release T3 / Thyromax was aardig wat aandacht:
- http://schildkliertje.blogspot.nl/2013/ ... aagde.html
- https://www.facebook.com/schildklier.nl ... 4193358874

Lees ook hier over Thyromax: http://www.schildklier-forum.nl/viewtop ... romax#p828

[laura]

Bron: Thyroid. December 2014, 24(12): 1670-1751. doi:10.1089/thy.2014.0028

A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care.

This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment.

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement
Jacqueline Jonklaas, Antonio Bianco, Andrew Bauer, Kenneth Burman, Anne Cappola, Francesco Celi, David Cooper, Brian Kim, Robin Peeters, Sara Rosenthal, Anna Sawka

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Methods
Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force.

Results
We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non–levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones.

Conclusions
We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine–liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.

Clearly, there have been great advances in the understanding and management of TH replacement, but nevertheless more research is needed. Areas in which future research should be encouraged include, but are not limited to:
1. Strategies to avoid iatrogenic thyroid disease in individuals treated for hypothyroidism.
2. Research into strategies to aid compliance with LT4 therapy.
3. Better understanding of maternal-fetal physiology during pregnancy with development of improved titration of LT4 therapy in hypothyroid pregnant patients.
4. Further studies of soft gel LT4 capsules to determine their proper place in the therapeutic armamentarium.
5. Further study, and improved standardization, of compounded formulations of LT4 and/or LT3.
6. Development of additional biomarkers of euthyroidism, which may supplement the use of serum TSH as a biomarker.
7. Development of a better understanding of how T3 levels are affected by age and disease status, with consideration of reference ranges indexed to age and health status.
8. Clarification of the relative importance of maintaining specific serum T3 concentrations.
9. Research into the relationship between serum T3 and T3 concentrations in specific tissues.
10. Development of more accurate assays to measure serum concentrations of FT3, total T3, and FT4.
11. Development of a sustained release T3 preparation that can then be prospectively tested in clinical trials (e.g., in combination with LT4 in a physiologic ratio of about 14:1).
12. In the absence of the availability of a sustained release T3 preparation, study of when, if ever, the use of LT3 would be beneficial in selected patients with apparent decreased T4 to T3 conversion and disproportionately low serum T3 levels.
13. Long-term outcome research using thyroid extracts that includes documentation of the consequences of excursions in serum T3 concentrations.
14. Development of TH analogs with a favorable benefit to risk profile.
15. Pursuit of research into developing thyroid stem cells as a potential avenue for understanding thyrocyte physiology and as a possible future treatment for hypothyroidism.