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Subclinical HypothyroidismA Review

Educational Objective
To learn about the underlying etiologies, clinical relevance, and management strategies of subclinical hypothyroidism.
1 Credit CME

Importance  Subclinical hypothyroidism, defined as an elevated serum thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) level with normal levels of free thyroxine (FT4) affects up to 10% of the adult population.

Observations  Subclinical hypothyroidism is most often caused by autoimmune (Hashimoto) thyroiditis. However, serum thyrotropin levels rise as people without thyroid disease age; serum thyrotropin concentrations may surpass the upper limit of the traditional reference range of 4 to 5 mU/L among elderly patients. This phenomenon has likely led to an overestimation of the true prevalence of subclinical hypothyroidism in persons older than 70 years. In patients who have circulating thyroid peroxidase antibodies, there is a greater risk of progression from subclinical to overt hypothyroidism. Subclinical hypothyroidism may be associated with an increased risk of heart failure, coronary artery disease events, and mortality from coronary heart disease. In addition, middle-aged patients with subclinical hypothyroidism may have cognitive impairment, nonspecific symptoms such as fatigue, and altered mood. In the absence of large randomized trials showing benefit from levothyroxine therapy, the rationale for treatment is based on the potential for decreasing the risk of adverse cardiovascular events and the possibility of preventing progression to overt hypothyroidism. However, levothyroxine therapy may be associated with iatrogenic thyrotoxicosis, especially in elderly patients, and there is no evidence that it is beneficial in persons aged 65 years or older.

Conclusions and Relevance  Subclinical hypothyroidism is common and most individuals can be observed without treatment. Treatment might be indicated for patients with subclinical hypothyroidism and serum thyrotropin levels of 10 mU/L or higher or for young and middle-aged individuals with subclinical hypothyroidism and symptoms consistent with mild hypothyroidism.

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Article Information

Corresponding Author: David S. Cooper, MD, Division of Endocrinology, Diabetes, and Metabolism, The Johns Hopkins University School of Medicine, 1830 E Monument St, Ste 333, Baltimore, MD 21287 (

Author Contributions: Dr Cooper had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: Cooper, Cappola.

Drafting of the manuscript: All authors.

Critical revision of the manuscript for important intellectual content: Cooper.

Supervision: All authors.

Conflict of Interest Disclosures: None reported.

Disclaimer: Dr Cappola is an associate editor of JAMA, but she was not involved in any of the decisions regarding review of the manuscript or its acceptance.

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