Reversible morbidity markers in subclinical hypothyroidism

Abstract

Importance. Subclinical hypothyroidism (SCH) is a common clinical entity with a putative role in a wide range of disorders. The impact of SCH on mortality and markers of morbidity has been demonstrated, but studies have shown inconsistent results. Evidence regarding the effect of levothyroxine treatment on reversing morbidity markers is emerging, but the value of treatment is still unclear. Objective. The objectives of this review were to assess recent, high-quality studies evaluating the role of SCH in cardiovascular health, cognition, mood, pregnancy, anemia, and renal disease; to examine the effects of levothyroxine on reducing mortality or reversing markers of morbidity in these conditions; and to consider how new research insights may help guide clinical practice. Evidence review. A PubMed search was conducted (using ‘subclinical hypothyroidism’ [Title/Abstract] AND morbidity [MeSH Subheading] as search criteria) and was restricted to human studies published in the English language between 1990 and 2013. Subsequent searches of retrieved articles yielded further studies, which were included based on quality. Emphasis was given to large observational studies, well-conducted meta-analyses, and randomized controlled trials. Findings. The difficulty of diagnosing SCH, particularly in the elderly, may underlie many of the conflicting results seen in the literature. Increased understanding of the at-risk patient population will result in better selection of study subjects and, likely, unequivocal results. Regardless of the current confusion, emerging evidence suggests that certain markers of morbidity are reversed by levothyroxine therapy across the disorders examined here. Conclusion and relevance. Future large, well-controlled studies will not only clarify the role of SCH but also help identify patients for whom levothyroxine treatment will provide the most benefit.

Keywords:

• cardiovascular morbidity
• cognitive function
• levothyroxine therapy
• morbidity
• subclinical hypothyroidism

Acknowledgments

Mariana Ovnic, PhD, of Complete Publication Solutions, Horsham, PA, USA, provided medical writing and editorial support to the authors in the development of this manuscript. Financial support to Complete Publication Solutions for medical writing and editorial assistance was provided by AbbVie. AbbVie provided suggestions for topic ideas and authors for this manuscript. AbbVie had the opportunity to review and comment on the manuscript. This manuscript reflects the opinions of the authors as to the scope of the endeavor, the focus of review, the methods for identifying the most recent literature, and the addition of relevant citations of great clinical importance. Each author reviewed the manuscript, providing extensive comment on the main clinical points to be emphasized, limitations of the literature cited, and relevance of these limitations to apply the information to clinical care, at all stages of development. Ramon Espaillat, an employee of AbbVie, is one of the authors of this manuscript and was involved in the development and review of the manuscript with the other author and the medical writer. The authors determined final content, and both authors read and approved the manuscript. The authors maintained complete control over the content of the manuscript. No payment was made to the authors for the writing of the manuscript.

Declaration of interest

The authors have received no financial support in conceiving of, planning, researching, editing, and directing the completion of this manuscript. J. V. Hennessey has received consulting fees from AbbVie for the education of personnel in bioequivalence issues and FDA labeling of levothyroxine in 2013. R. Espaillat is an AbbVie employee and may hold AbbVie stock or stock options.

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