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Thyroid Disease: Guidelines for Diagnosis and Management

Posted January 1, 2005

Hyperthyroidism and hypothyroidism are common conditions that have lifelong effects on health. About 5% of U.S. adults report having thyroid disease or taking thyroid medication at some time. Thyroid dysfunction, which can be diagnosed by thyroid function tests, is usually readily treatable. Clinical manifestations are often insidious and vary considerably among patients. If symptoms alone were relied on for diagnosis, many patients would go untreated. Consequently, physicians are more often excluding hypothyroidism or hyperthyroidism through routine laboratory screening, rather than establishing thyroid disease as their primary diagnosis. The goal of screening is to identify patients with subclinical thyroid dysfunction and to treat them before they develop symptoms and complications of their disease.

Serum thyroid stimulation hormone (TSH) measurement is the single most reliable test to screen for and to diagnose all common forms of hypothyroidism and hyperthyroidism. Most labs now use third-generation TSH assays, which have detection sensitivity of less than 0.02 mU/L. These assays generally show a specificity of greater than 99% and positive predictive values over 96%. If less sensitive assays are employed, a free-T4 assay and a total or free-triiodothyronine (T3) assay should be performed at the time of screening to reliably distinguish hyperthyroid patients from euthyroid patients. About 85% of ambulatory patients without associated disease or pituitary dysfunction will have normal TSH values and do not require further testing.

In both subclinical (normal free-T4) and clinical hypothyroidism (decreased free-T4), the TSH will be elevated. The only exception to this is secondary (central) hypothyroidism (e.g. TSH secreting pituitary adenoma or thyroid hormone resistance), which only accounts for about 1% of the cases. Primary thyroid disease accounts for over 99% of the cases of hypothyroidism. In secondary hypothyroidism the TSH is usually normal, but may be low or even mildly elevated. If secondary disease is suspected, a free-T4 must be performed along with TSH. If subclinical or clinical hypothyroidism is present, testing for thyroid peroxidase antibodies (TPOAb) should be performed to rule out an autoimmune mechanism (e.g. Hashimoto thyroiditis).

Virtually all commonly encountered types of hyperthyroidism show suppressed serum TSH, typically less than 0.1 mU/L. Serum free-T4 measurement is indicated to further assess the severity of hyperthyroidism in those patients with a serum TSH level less than 0.1 mU/L. If the serum TSH is decreased and the free-T4 is normal, total or free-T3 must be performed to rule out T3 toxicosis. If Graves’ disease is suspected, testing for TSH receptor antibodies (TRAb) should be performed.

The American Thyroid Association and the U.S. Preventative Services Task Force have advocated screening asymptomatic adults with serum TSH at age 35 years and every 5 years thereafter, but the cost-effectiveness of this is still controversial. More frequent screening may be appropriate in individuals at higher risk of developing thyroid dysfunction. Screening of newborn children for hypothyroidism is already a widely accepted and legislatively mandated practice.

There are effective therapies for both hypothyroidism and hyperthyroidism for patients in whom treatment is indicated, such as in high-risk patients with, for example, hyperlipidemia, atrial fibrillation or reduced bone mineral density. It is still uncertain whether treatment will improve the quality of life in otherwise healthy patients who have subclinical thyroid disease.

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NewsPath® Editor: Megan J. DiFurio, MD, FCAP
This newsletter is produced in cooperation with the College of American Pathologists Public Affairs Committee and may be reproduced in whole or in part as a service to the medical community. Copyright © 2006 by the College of American Pathologists.
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