CLINICAL THYROIDOLOGY FOR THE PUBLIC
A publication of the American Thyroid Association
Some patients with apparent Graves’ disease do not have an autoimmune thyroid disorder
One of the most common causes of hyperthyroidism is Graves’ disease, an autoimmune process in which the patient’s immune cells make antibodies against the thyroid stimulating hormone (TSH) receptor on the thyroid gland cells. These autoantibodies stimulate the thyroid to grow, resulting in a diffuse enlargement (goiter), and to produce excessive amounts of thyroid hormone, resulting in hyperthyroidism. Graves’ disease with hyperthyroidism is characterized by the presence of diffuse thyroid enlargement, suppression of pituitary TSH, elevations of thyroxine (T4) and/or triiodothyronine (T3), the presence of TSH receptor antibodies in the blood, an elevated radioactive iodine uptake by the thyroid gland and clinical symptoms such as weight loss, increased perspiration, anxiety, tremor, rapid heart rate and frequent bowel movements. Some patients with Graves’ disease may have subclinical (mild) hyperthyroidism without symptoms but with a goiter, suppressed TSH, TSH receptor antibodies, but with normal T4 and T3. Although TSH receptor antibodies are detected in the majority of patients with Graves’ disease, there are some patients in whom such antibodies cannot be detected, but yet appear to have typical Graves’ disease. Some of the antibody negative patients may actually have Graves’ disease but the antibody levels are too low to detect initially. A small number of the patients may have a mutation of the TSH receptor resulting in the receptor being chronically turned on causing diffuse enlargement of the thyroid and clinical or subclinical hyperthyroidism. This would resemble the clinical and biochemical findings with Graves’ disease but without the antibodies.
The present study was designed to look at a large number of patients with hyperthyroidism, diffuse goiters, but no measurable TSH receptor antibodies to see if the cause of the hyperthyroidism could be determined.
THE FULL ARTICLE TITLE:
Nishihara E et al, The prevalence of TSH receptor germline mutations and clinical courses in 89 hyperthyroid patients with diffuse goiter and negative anti-TSH receptor antibodies. Thyroid. November 26, 2013 [Epub ahead of print].
SUMMARY OF THE STUDY
Over a 10 year period, close to 25,000 patients with hyperthyroidism were evaluated at Kuma Hospital in Japan. From this group, 89 patients had diffuse goiters with negative TSH receptor antibodies. About 10% of the 68 patients who were followed for more than a year developed TSH receptor antibodies and another 6% had weakly positive antibody levels, suggesting that they actually had mild Graves’ disease when first seen and then evolved into more typical Graves’ disease. A total of 4 of the 89 patients were found to have mutations in the thyroid TSH receptor that was responsible for the goiter and hyperthyroidism. Screening of family members of these patients identified an additional 7 patients with the mutations and all had subclinical or overt hyperthyroidism, while the other family members without the mutation had normal thyroid function. Patients with the mutations did not have a spontaneous remission of the hyperthyroidism with or without antithyroid drugs, unlike some patients with Graves’ disease who may go into remission either spontaneously or after a course of antithyroid drug treatment.
WHAT ARE THE IMPLICATIONS OF THIS STUDY?
In this series of patients, about 5% of the 89 adult patients who clinically appeared to have Graves’ disease but did not have TSH-receptor antibodies in their blood had activating mutations of the TSH receptor causing the hyperthyroidism and some of these mutations were found in other family members indicating that the disorder runs in families. Approximately 10-15% of the 89 patients actually had Graves’ disease that became apparent over time. Thus, the cause of the hyperthyroidism in the majority of the patients remained undefined. Nevertheless, the standard therapies of antithyroid drugs, radioactive iodine, or surgery can be used in these patients irrespective of the cause. Importantly, the antithyroid drugs will not bring about a remission for those with TSH receptor mutations.
—Glenn D. Braunstein, M.D.
ATA THYROID BROCHURE LINKS
Graves’ disease: http://www.thyroid.org/what-is-graves-disease