Article

The nonthyroidal illness syndrome

Georgetown University, Washington, Washington, D.C., United States
Endocrinology & Metabolism Clinics of North America (Impact Factor: 2.86). 10/2007; 36(3):657-72, vi. DOI: 10.1016/j.ecl.2007.04.007
Source: PubMed

ABSTRACT This article briefly summarizes thyroid function alterations generally seen in the euthyroid sick syndrome, provides an overview of specific thyroidal adaptations during several clinical conditions and secondary to specific pharmacologic agents, and discusses the current controversy in thyroid hormone treatment of nonthyroidal illness.

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    ABSTRACT: Background 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 committee 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. Methods Committee 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 the clinical recommendations was assessed, using the American College of Physicians (ACP) system. 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 (eg. 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: development of superior biomarkers of euthyroidism to supplement TSH 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 sub-group effects) Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.
    Thyroid: official journal of the American Thyroid Association 09/2014; DOI:10.1089/thy.2014.0028 · 3.84 Impact Factor

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