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First published online on November 8, 2007
Endocrine Reviews, doi:10.1210/er.2006-0043
A more recent version of this article appeared on February 1, 2008
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The Clinical Significance of Subclinical Thyroid Dysfunction

Bernadette Biondi* and David S. Cooper

Department of Clinical and Molecular Endocrinology and Oncology, University of Naples Federico II, 80131 Naples, Italy; and Sinai Hospital of Baltimore, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21215

* To whom correspondence should be addressed. E-mail: bebiondi{at}unina.it.

Subclinical thyroid disease (SCTD) is defined as serum FT4 and FT3 levels within their respective reference ranges in the presence of abnormal serum thyrotropin-stimulating hormone levels. Subclinical thyroid disease is being diagnosed more frequently in clinical practice in young and middle-aged people as well as in the elderly. However, the clinical significance of subclinical thyroid dysfunction is much debated. Subclinical hyper- and hypothyroidism can have repercussions on the cardiovascular system and bone, as well as on other organs and systems. However, the treatment and management of SCTD and population screening are controversial despite the potential risk of progression to overt disease, and there is no consensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms and signs, and the cardiovascular risk. Here we critically review the data on the prevalence and progression of SCTD, its tissue effects, and its prognostic implications. We also examine the mechanisms underlying tissue alterations in SCTD and the effects of replacement therapy on progression and tissue parameters. Lastly, we address the issue of the need to treat slight thyroid hormone deficiency or excess in relation to the patient's age.


Key words: hyperthyroidism • hypothyroidism • subclinical thyroid disease • subclinical hyperthyroidism (exogenous and endogenous) • subclinical hypothyroidism




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