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 decrease when the thyroid gland produces excess levels of thyroid hormone.

Subclinical Hyperthyroidism An asymptomatic condition in which patients have low TSH levels with normal serum thyroid hormone levels. There are many underlying causes of this condition, such as Graves’ disease, thyroid nodules, and treatment with thyroid hormone (levothyroxine)

What is the study about? More patients with TSH levels <0.05 mIU/L progress to overt hyperthyroidism than those with serum TSH levels ranging from 0.05 to 0.1 mIU/L.

The full article title: “The natural history of subclinical hyperthyroidism in patients below the age of 65 years.” It is in the March 2008 Issue of Clinical Endocrinology (Oxf) (Volume 68 Issue 3, pages 491-92). The author is PW Rosario. The abstract can be obtained from:

What is known about the problem being studied? Although it usually does not progress to overt hyperthyroidism, subclinical hyperthyroidism it is more common with very low serum TSH. It has been suggested that the course of subclinical hyperthyroidism is influenced by its cause, with a higher rate of spontaneous cessation in Graves’ disease, but most such studies have been conducted on individuals over 60 years of age.

What was the aim of the study? This study was aimed at identifying the course of subclinical hyperthyroidism in a patient cohort younger than age 60 years.

Who was studied? Sixty women younger than 65 years old were enrolled in the study if their serum TSH was <0.1 mIU/L (the level that denotes thyrotoxicosis) and they had no elevations of serum thyroid hormone levels or a history of thyroid disease or other conditions that might interfere with the study.

How was the study done? The study subjects underwent a 2-year follow-up period during which they had no therapeutic interventions. Thyrotoxicosis was caused by Graves’ disease in 31% of the study subjects and 50% had toxic multinodular goiter or a single toxic nodule. Patients had serial thyroid function tests during the study period.

What were the results of the study? Serum TSH spontaneously returned to normal in 20% of the patients with nodular disease and in 13% with Graves’ disease, and TSH improved in 27% with nodular disease and in 20% with Graves’ disease. Subclinical hyperthyroidism persisted in 33.3% with nodular disease and in 27% with Graves’ disease. Among patients with very low serum TSH levels, overt hyperthyroidism developed in 26% with nodular thyroid disease and 50% with Graves ’ disease and only 4 patients developed overt hyperthyroidism.

How does this compare with other studies? Earlier studies that have addressed the question of the evolution of subclinical hyperthyroidism involved elderly patients of whom most had subclinical hyperthyroidism associated with multinodular goiter. These studies collectively indicated that a subnormal serum TSH is more likely to persist in patients with goiter or when the initial serum TSH value is <0.1 mIU/L and that only a minority of patients progress to overt hyperthyroidism. This is in contrast to the findings in this study.

What are the Limitations of this study? Studies show that patients with subclinical thyroid dysfunction often have thyroid function tests that undergo rapid and dramatic swings over several years when they have not been subject to therapy.

What are the implications of this study? More patients with TSH levels <0.05 mIU/L progress to overt hyperthyroidism than those with serum TSH levels ranging from 0.05 to 0.1 mIU/L.

Patients younger than 65 years of age who have subclinical hyperthyroidism have a somewhat different outcome than older patients, depending on the cause of the disease. After a 2-year followup period without therapeutic intervention, the progression rate to overt hyperthyroidism is about 10% per year for toxic nodular disease and about 20% for Graves’ disease. Serum TSH levels spontaneously return to normal in more patients with toxic nodular disease than in patients with Graves’ disease. These results are very different than those in older patients.

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