Subclinical Hypothyroidism and Cardiovascular Disease

Subclinical thyroid disease (SCTD) is defined as serum free T 4 and free T 3 levels within their respective reference ranges in the presence of abnormal serum TSH levels. SCTD 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 con-sensus on the thyroid hormone and thyrotropin cutoff values at which treatment should be contemplated. Opinions differ regarding tissue effects, symptoms, signs, and 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. (Endocrine Reviews 29: 76 -131, 2008) I. Introduction II. Methods A. Identification of sources B. Methods of evaluation to assess study quality III. Normal Thyrotropin-Stimulating Hormone Range IV. Set-Point of the Hypothalamic-Pituitary-Thyroid Axis and Individual TSH Range V. Subclinical Hypothyroidism A. Subclinical hypothyroidism and minimally increased TSH B. Etiology of subclinical hypothyroidism C. Differential diagnosis of serum TSH elevation D. Prevalence of subclinical hypothyroidism E. Natural history of subclinical hypothyroidism F. Symptoms, quality of life, and cognitive function in subclinical hypothyroidism G. Cardiovascular risk in subclinical hypothyroidism H. Subclinical hypothyroidism and neuromuscular dysfunction I. Effects of replacement therapy J. Thyroid hormone deficiency before and during pregnancy K. Subclinical hypothyroidism in the elderly L. Subclinical hypothyroidism in children M. Screening for hypothyroidism N. Treatment of subclinical hypothyroidism VI. Subclinical Hyperthyroidism A. Subclinical hyperthyroidism and minimally suppressed TSH B. Etiology of subclinical hyperthyroidism C. Differential diagnosis in subclinical hyperthyroidism D. Prevalence of subclinical hyperthyroidism E. Natural history of subclinical hyperthyroidism F. Symptoms and quality of life in subclinical hyperthyroidism G. Subclinical hyperthyroidism, mood, and cognitive function H. Cardiovascular risk in subclinical hyperthyroidism I. Subclinical hyperthyroidism and bone and mineral metabolism J. Effects of treatment K. Treatment guidelines