Graves’ Disease

Posted by • October 20th, 2016

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Graves’ disease is an autoimmune disorder in which the thyroid is activated by antibodies to the thyrotropin receptor. The hyperthyroidism that develops is one of many somatic and psychiatric manifestations of the disease that can affect the quality and length of life. The disease is the most common cause of hyperthyroidism, with an annual incidence of 20 to 50 cases per 100,000 persons. The incidence peaks between 30 and 50 years of age, but people can be affected at any age. The lifetime risk is 3% for women and 0.5% for men. A new Review Article summarizes.

Clinical Pearl

• How common is Graves’ ophthalmopathy?

Orbital imaging reveals subtle abnormalities in 70% of patients with Graves’ disease. In specialized centers, clinically consequential ophthalmopathy is detected in up to 50% of patients with Graves’ disease, and it threatens sight as a consequence of corneal breakdown or optic neuropathy in 3 to 5% of such patients.

Clinical Pearl

• How does patient age influence the clinical manifestations of Graves’ disease?

The manifestations of Graves’ disease depend on the age of the patient at the onset of hyperthyroidism, as well as the severity and the duration of hyperthyroidism. Weight loss, decreased appetite, and cardiac manifestations are more common in elderly persons with hyperthyroidism than in those who are younger. Atrial fibrillation due to hyperthyroidism is rare in patients who are younger than 60 years of age but occurs in more than 10% of patients who are 60 years or older. Palpable goiter develops in most patients with hyperthyroidism who are younger than 60 years of age, as compared with less than 50% of older patients. Severe ophthalmopathy is more likely to develop in older men than in younger persons.

Morning Report Questions

Q: What percentage of patients with Graves’ disease who are treated with methimazole and propylthiouracil have a durable remission? 

A: Methimazole, carbimazole (which is converted to methimazole and is not available in the United States), and propylthiouracil inhibit thyroid peroxidase and thus block thyroid hormone synthesis. Propylthiouracil also blocks extrathyroidal deiodination of thyroxine to triiodothyronine. Both methimazole and propylthiouracil are associated with a high risk of recurrence after treatment has been withdrawn. Durable remission occurs in 40 to 50% of patients. Repeated therapy carries an even lower likelihood of success.

Q: How does thyroid-associated ophthalmopathy present, and how is it treated?

A: Hyperthyroidism and ophthalmopathy typically occur within 1 year of each other but can be separated by decades. Disease development is heralded by an active phase lasting up to 3 years and dominated by evolving symptoms and signs of inflammation and congestion. Proptosis, eyelid swelling, and diplopia may prompt initial medical attention. Some patients have dry eye, increased tearing, and ocular discomfort early in the active phase. This is followed by an inactive phase in which the ocular manifestations become stable. In a cohort of consecutively assessed patients with Graves’ disease, the prevalence of distinct abnormalities was as follows: eyelid retraction, 92%; exophthalmos, 62%; extraocular muscle dysfunction, 43%; ocular pain, 30%; increased lacrimation, 23%; and optic neuropathy, 6%. Treatment for ophthalmopathy depends on the phase and severity of the disease. The majority of patients require only conservative measures. These include enhancement of tear-film quality and maintenance of ocular surface moisture. Patients with disease that is severely symptomatic and sight-threatening may benefit from intravenously administered pulse glucocorticoid therapy, which appears to have a more favorable side-effect profile than glucocorticoids administered orally, although pulse therapy is not without risks. Glucocorticoids are frequently effective in reducing inflammatory symptoms, but most experts do not believe that they modify the course of the disease. Orbital decompression surgery during active disease is usually reserved for patients in whom compressive optic neuropathy has developed or is imminent.

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