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American Thyroid Association Guide to Investigating Thyroid Hormone

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American Thyroid Association Guide to Investigating Thyroid Hormone THYROID Volume 24, Number 1, 2014 ª American Thyroid Association DOI: 10.1089/thy.2013.0109 American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models Report of the American Thyroid Association Task Force on Approaches and Strategies to Investigate Thyroid Hormone Economy and Action Antonio C. Bianco,1,* Grant Anderson,2 Douglas Forrest,3 Valerie Anne Galton,4 Bala´zs Gereben,5 Brian W. Kim,1 Peter A. Kopp,6 Xiao Hui Liao,7 Maria Jesus Obregon,8 Robin P. Peeters,9 Samuel Refetoff,7 David S. Sharlin,10 Warner S. Simonides,11 Roy E. Weiss,7 and Graham R. Williams12 Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyper- thyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes. INTRODUCTION nostic and therapeutic tools are based. Tens of thousands of publications indexed on PubMed (www.pubmed.gov) fea- ver the past 150 years, investigators utilizing animal ture cells or small animals made hypothyroid or thyrotoxic. Oand cell culture–based experimental models have The great similarities in multiple aspects of thyroid physi- achieved landmark discoveries that have shaped our under- ology between humans and small rodents have facilitated the standing of thyroid physiology and disease. From the iden- rapid translation of experimental findings to the clinical tification of the long-acting thyroid stimulator to the realm. At the same time, fundamental interspecies differences discovery of antithyroid drugs, basic research studies have do exist and must be carefully accounted for if the experi- provided the fundamentals upon which our clinical diag- mental findings are to have clinical relevance. 1Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, Miami, Florida. 2Department of Pharmacy Practice and Pharmaceutical Sciences, College of Pharmacy, University of Minnesota Duluth, Duluth, Minnesota. 3Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 4Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon, New Hampshire. 5Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. 6Division of Endocrinology, Metabolism, and Molecular Medicine, and Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 7Section of Adult and Pediatric Endocrinology, Diabetes, and Metabolism, The University of Chicago, Chicago, Illinois. 8Institute of Biomedical Investigation (IIB), Spanish National Research Council (CSIC) and Autonomous University of Madrid, Madrid, Spain. 9Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. 10Department of Biological Sciences, Minnesota State University, Mankato, Minnesota. 11Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. 12Department of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom. *Chair; all other authors are listed in alphabetical order. 88 INVESTIGATING THYROID HORMONE ECONOMY AND ACTION 89 While certain experimental techniques have been widely METHODS OF DEVELOPMENT accepted and adapted following their use in papers gener- OF RECOMMENDATIONS ated by influential labs, lack of standardization has un- Administration doubtedly promoted heterogeneity of results. Because certain experimental variables may have unknown biologi- The ATA Executive Council selected a chairperson to lead the cal threshold levels, lack of standardization may lead to have task force, and this individual (A.C.B.) identified the other 14 highly discordant results in different studies examining the members of the panel in consultation with the ATA board of same issue. directors. Membership on the panel was based on expertise and To address this lack of standardization, the American previous contributions to the thyroid field. Panel members de- Thyroid Association (ATA) convened a panel of specialists in clared whether they had any potential conflict of interest during the field of basic thyroid research to define consensus strate- the course of deliberations. Funding for the guide was derived gies and approaches for thyroid studies in rodents and in cell from the ATA and thus the task force functioned without models. This task force was charged with reviewing the lit- commercial support. erature first to determine which experimental practices could To develop a useful document, the task force first devel- benefit from standardization and second to identify critical oped a list of the topics that would be most helpful and the experimental variables that demand consideration when most important questions that scientists working in the thy- thyroid studies are being designed. The conclusions of the roid field might pose when planning an experiment or inter- task force are presented in this document as ‘‘American preting experimental data. Each of the 10 topics was Thyroid Association Guide to Investigating Thyroid Hor- distributed to a primary writer who used his or her knowl- mone Economy and Action in Rodent and Cell Models.’’ The edge of the subject as well as a systematic PubMed and 70 recommendations and their accompanying commentaries Google Scholar search for primary references, reviews, and examine topics ranging from ‘‘making cells hypothyroid’’ to other materials publicly available before December 2012, to ‘‘how to study the thyrotoxic bone.’’ While far from exhaus- develop a set of recommendations. All drafts were reviewed tive, these recommendations touch on certain fundamental and edited by the chair for consistency and sent back to the aspects of thyroid research relevant for all investigators in primary writers for review; in some cases multiple iterations the field. took place until the recommendation was finalized. A pre- Each recommendation in this guide promotes a particular liminary draft of each recommendation was then reviewed by experimental approach based on criteria including the secondary and tertiary reviewers within the group who then prevalence of the approach, with widely used techniques prepared additional critiques. These were addressed by the being given precedence, and in particular whether the ap- primary writer and sent back to the chair. All drafts were proach has been shown to lead to reproducible results in merged and posted at a protected web address available only studies by independent investigators. Because head-to-head to the task force members and ATA office. This document scientific comparisons of experimental methods in this field remained available for periodic review by the task force at are virtually nonexistent, these recommendations cannot be large, with critiques and suggestions sent back to the chair graded on the basis of strength of evidence in the fashion of that updated the document. In a few cases the chair asked for clinical guidelines; indeed, all would be graded as ‘‘expert outside experts to critically review specific recommendations opinion.’’ At the same time, unlike clinical guidelines, the given their expertise in a focused area. Their comments and main goal of these recommendations and their accompany- suggestions were then worked into the master document, and ing commentaries is not to identify the single best practice the contributions are acknowledged at the end of this article. per se, but instead to encourage investigators to choose The panel agreed that recommendations would be based standard approaches; for example, avoiding random treat- on consensus of the panel. Task force deliberations took place ment doses or methods of thyroid hormone administration, largely through electronic communication. There were also a which would only serve to limit comparison with previous few meetings of the authors and telephone conference calls. studies. The practical nature of recommendations should become Presentation, Approval, and Endorsement readily apparent to the reader. This document is intended of Recommendations to serve as a reference for investigators, assisting them in making design choices that avoid well-known pitfalls The structure of our recommendations is presented in Table while increasing standardization in the field. As part of 1. Specific recommendations are presented within the main this practical approach, reference credit is often given to body of the text and in many cases broken down in subitems manuscripts in which the technical details
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