Graves disease is the most common cause of hyperthyroidism in the United States. Other causes of hyperthyroidism include multinodular goiter, toxic solitary nodules of the thyroid, and functioning thyroid cancer. Rare causes for hyperthyroidism include TSH-secreting pituitary tumors, struma ovarii, and hCG-secreting trophoblastic tumors of the ovary or testis. All of the latter conditions cause increased thyroid radioactive iodine uptake on scanning. Hyperthyroidism without increased thyroid radioiodine uptake can be caused by subacute thyroiditis, an acute phase of Hashimoto thyroiditis, thyroid hormone intake, and iodide-induced hyperthyroidism (due to kelp, amiodarone, x-ray contrast, or potassium iodide).
Symptoms of Graves disease are those of hyperthyroidism and may include anxiety, restlessness, irritability, emotional instability, inability to concentrate, fatigue, muscle weakness or cramps, heat intolerance, and increased sweating. Periodic paralysis with low potassium may occur in men with hyperthyroidism who are of Asian, Filipino, or Native American ethnic backgrounds. Cardiac symptoms can include palpitations with a fast or forceful heartbeat, shortness of breath, atrial fibrillation, or angina. Patients may also have a tremor, eye stare, and changes in hair. Osteoporosis can occur if hyperthyroidism becomes chronic and is left untreated. Women experience menstrual irregularities. Bowel movements may become more frequent.
Patients usually lose weight, despite a good appetite; but an occasional patient ironically gains weight because hyperthyroidism usually increases appetite. Oprah Winfrey said of her Graves disease: “Hyperthyroidism sped up my metabolism and left me unable to sleep for days. Most people lose weight. I didn’t.”
American top pro tennis pro Mardy Fish reportedly developed Graves disease at age 29. His presenting symptoms were unusual fatigue and muscle weakness. As a result, he lost to an underdog in the second round of the 2011 Australian open. Fish reported: “The thyroid problem is strange. It sort of zaps you. You don’t feel really ill or anything but just a little helpless.”
Hip hop singer Missy Elliott was diagnosed with Graves disease after experiencing dizzy spells, mood swings, hair loss, a fast heart rate, and bulging eyes. Other celebrities with Graves disease have included pop singers Toni Childs and Kelly Osbourne, actress Faith Ford, and NASCAR driver Bobby Labonte.
Most, bot not all, patients with Graves disease have an enlarged thyroid (goiter). Skin myxedema is unusual. The myxedema seen with Graves disease makes the affected skin appear somewhat like an orange skin, thus the term “peau d’orange.” Skin myxedema usually affects the shins, where it is known as “pretibial myxedema”, but it may affect other areas of skin.
Treatment for hyperthyroidism is directed at the cause of the problem. For Graves disease, patients and their physicians have the option of treatment with thionamides (eg. methimazole or PTU), surgery, or radioactive iodine. Symptomatic relief may be obtained from the beta  blocker propranolol.
Graves eye disease (ophthalmopathy, thyroid associated orbitopathy) came to national attention when First Lady Barbara Bush developed Graves disease with exophthalmos (eye protrusion). Her husband, President George Bush, also had Graves disease. Suspecting a plot, the Secret Service investigated this, but it was finally considered coincidental. Exophthalmus develops in only a minority of patients with Graves disease, but the risk is greatly increased in smokers.
People with Graves eye disease may have involvement of one or both eyes to variable degrees. Occasionally, thyroid eye disease occurs without noticeable enlargement of the thyroid gland or any hyperthyroidism. Although nearly 50% of patients with Graves disease have some eye complaints, only about 5% develop exophthalmos that is serious enough to warrant treatment. Thyroid eye disease is not particularly helped by removing the thyroid gland or by treatment with radioactive iodine. In fact, radioactive iodine can aggravate Graves eye disease. Once hyperthyroidism is treated, the eyes can appear improved, since achieving normal thyroid levels reduces the stare and retraction of the eyelid muscles. For mild-to-moderate Graves eye disease, selenium supplementation 200 mcg/d has been shown to improve outcome. But when Graves exophthalmus becomes very noticeable or affects vision, aggressive treatment with prednisone must be commenced immediately. For patients with active prednisone-resistant Graves eye disease, off-label use of other drugs, such as the IL-6 inhibitor Actemra (tocilizumab) may slow the disease. Some patients require additional therapy with radiation therapy to the retro-orbital muscles. If eye protrusion becomes permanent and to correct diploplia (double vision), orbital decompression surgery can be performed.
