A publication of the American Thyroid Association

Summaries for Patients from Clinical Thyroidology by Ernest Mazzaferri, MD MACP

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Abbreviations & Definitions

TSH Thyroid stimulating hormone (thyrotropin) is a pituitary hormone that stimulates the release of thyroid hormone from the thyroid gland.TSH levels increase when the thyroid gland fails to make sufficient thyroid hormone.

Reference Limit The upper normal limit of TSH above which doctors begin considering thyroid hormone therapy.

HDTS The Hanford Thyroid Disease study comprises people in the state of Washington who, during the 1940s and 1950s, were exposed as children to radioiodine (131I) emissions from the Hanford nuclear facility and were considered to be at increased risk for thyroid disease. However, the study found no connection between 131I exposure and thyroid disease.

Subclinical Hypothyroidism An asymptomatic condition in which patients have elevated serum TSH levels with normal serum thyroid hormone levels.

NHANES III is the third National Health and Nutrition Examination Survey. It can be found at:

What is the study about? Lowering the thyrotropin reference limit to 2.5 μIU/ml may result in inappropriate therapy for many euthyroid individuals

The full article title: “Thyrotropin levels in a population with no clinical, autoantibody or ultrasonographic evidence of thyroid disease: implications for the diagnosis of subclinical hypothyroidism.” It is in the July 2008 Issue of the Journal of Clinical Endocrinology and Metabolism (Volume 93 Issue 4, pages 1224-30). The authors are TE Hamilton, S Davis, L Onstad L, and KJ Kopecky. The abstract can be obtained from:
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What is known about the problem being studied? The normal upper serum TSH limit has been debated. Some suggest that it should be lowered from approximately 4.0 to 2.5 μIU/ml. This has major implications for the diagnosis and treatment of subclinical hypothyroidism, which could lead to millions of people worldwide being unnecessarily treated with thyroid hormone for a lifetime.

What was the aim of the study? This study was aimed at identifying the normal upper serum TSH range in healthy people

Who was studied? The study was performed on 1861 individuals with no clinical evidence of thyroid disease who were randomly selected from the HDTS population for measurement of serum TSH levels and neck ultrasonography.

How was the study done? Patients were divided into three normal reference groups that were selected with increasingly more stringent criteria to identify those without evidence of thyroid disease. TSH was retested by both older and contemporary laboratory methods.

What were the results of the study? The upper TSH reference limit was 4.1 μIU/ml in the most rigorously screened individuals who had no clinical evidence of thyroid dysfunction.

How does this compare with other studies? The results of this study were identical to the upper TSH limit of 4.12 μIU/ml in the NHANES III study. Data from NHANES III is available at the following:

What are the Limitations of this study? One potential limitation is that no data were collected on family histories of thyroid disease.

What are the implications of this study? Lowering the TSH reference limit to 2.5 μIU/ml may result in inappropriate therapy for many individuals with normal thyroid function that is not likely to deteriorate in the future.

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