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Wendy Williams' Battle With Graves' Disease

<ѻý class="mpt-content-deck">— The talk show host has taken a hiatus from her show, but what is she fighting?
MedpageToday

Talk show host Wendy Williams is taking some time off to deal with medical issues. The Wendy Williams Show took to with the announcement:

"Over the past few days, Wendy has experienced complications regarding her Graves' Disease that will require treatment. Wendy will be under the strict supervision of her physicians, and as part of her care, there will be significant time spent in the hospital."

"Despite her strong desire to return, she is taking a necessary, extended break from her show to focus on her personal and physical well-being. Wendy thanks everyone in advance for their well-wishes and for respecting her and The Hunter Family's privacy during this time."

It was just mid-December when Williams was seen wearing a sling on her show, reporting that she had a hairline fracture in her right shoulder.

Fans first became concerned about Williams' health in 2017, after she fainted during a live taping of her show on Halloween 2017. At the time, Williams claimed it was because she was overheated and had low electrolytes.

In February 2018, Wendy announced to viewers that she had Graves' disease, and had been living with it for years. She also said that it was the cause of her "bulgy" eyes. Fans had been pointing it out to her. Her physician now insisted that she take a three-week break to focus on her health.

What is Graves' disease?

Graves' disease is an autoimmune disorder that causes hyperthyroidism and is the most common cause of hyperthyroidism in the U.S. The disease affects about 1 in 200 people. Graves' disease usually affects people from ages 30 through 50 but can occur at any age. The disease is seven to eight times more common in women than men. A person's chance of developing Graves' disease increases if other family members have the disease.

People with other autoimmune disorders are more likely to develop Graves' disease than people without these disorders. Conditions linked with Graves' disease include:

  • rheumatoid arthritis
  • pernicious anemia
  • systemic lupus erythematosus
  • Addison's disease
  • celiac disease
  • vitiligo
  • type 1 diabetes

In Graves' disease, the immune system makes antibodies called thyroid-stimulating immunoglobulin (TSI). TSI mimics the action of TSH and stimulates the thyroid to make too much thyroid hormone.

What are the symptoms of Graves' disease?

People with Graves' disease (GD) may have some of the common symptoms of hyperthyroidism such as:

  • nervousness or irritability
  • fatigue or muscle weakness
  • heat intolerance
  • trouble sleeping
  • hand tremors
  • rapid and irregular heartbeat
  • frequent bowel movements or diarrhea
  • weight loss
  • goiter, which is an enlarged thyroid that may cause the neck to look swollen
  • Graves' ophthalmopathy

What is Graves' ophthalmopathy?

Grave's ophthalmopathy (GO) occurs when cells from the immune system attack the muscles and other tissues around the eyes. The result is inflammation and a buildup in tissue and fat behind the eye socket, causing the eyeballs to bulge (proptosis). Other symptoms of GO include:

  • dry, irritated eyes
  • puffy eyelids
  • double vision
  • light sensitivity
  • pressure or pain in the eyes
  • trouble moving the eyes

How is Graves' disease treated?

There are three established choices for the treatment of Graves' disease.

Radioiodine therapy (RAI): Radioiodine therapy is the most commonly used treatment for GD in the U.S. In radioiodine therapy, the patient takes radioactive iodine-131 by mouth. Because the thyroid gland collects iodine to make thyroid hormone, it will collect the radioactive iodine from the bloodstream in the same way. Iodine-131 gradually destroys the cells that make up the thyroid gland but will not affect other tissues in the body. Almost everyone who has RAI later develops hypothyroidism, which can be treated with thyroid hormone medication.

Over the past decade, there has been a decline in RAI usage and probably represents the treatment choice for less than 50% of new Graves' disease patients. A puts the failure rate of RAI at about 8%.

The advantages of RAI is that it can achieve a rapid control of hyperthyroidism with an approximate chance of an 80% cure (euthyroidism or hypothyroidism) in most patients. In addition, there is no risk of surgery or anesthesia. It is the preferred therapy in patients with surgical comorbidities, where antithyroid drugs are contraindicated or have failed, and in situations where rapid control of hyperthyroidism is important.

Thyroid surgery: Surgery is the least-used option in treating Graves' disease. However, doctors sometimes choose surgery to treat pregnant women who cannot tolerate antithyroid drugs, people in whom thyroid cancer is suspected, or those who fail other forms of treatment. Advantages include a rapid control of hyperthyroidism and the highest efficacy with a 100% success rate. It is useful for patients with large symptomatic or a co-existing thyroid cancer. It may be the preferred treatment for those with large goiters with compressive symptoms.

It should be noted that Graves' disease itself does not cause cancer.

Antithyroid drugs: Three antithyroid drugs, methimazole (MMI, in the U.S.), propylthiouracil (PTU), and Carbimazole (in Europe) have been available since the 1940s. They interfere with the thyroid peroxidase (TPO) enzyme, inhibiting thyroid hormone synthesis. ATDs are thought to have an additional immunomodulatory effect and are associated with a decrease in the thyroid receptor auto-antibody TRAb levels in many patients.

These medicines usually don't provide a permanent cure, but in some people, the effects last a long time after they stop taking the medicine. Doctors most often use the antithyroid medicine .

Doctors usually treat pregnant and breastfeeding women with antithyroid medicine, since this treatment may be safer for the baby than other treatments. Doctors use more often than methimazole during the first 3 months of pregnancy because methimazole may harm the fetus, although this happens rarely. Also rarely, propylthiouracil may affect the fetus, but any effects are less harmful than having uncontrolled hyperthyroidism during pregnancy.

Once treatment with antithyroid medicine begins, thyroid hormone levels may not move into the normal range for several weeks or months. The total average treatment time is about 12 to 18 months (), but treatment can continue for many years in people who don't want radioiodine or surgery to treat their Graves' disease.

Potential new treatment options:

A 2018 review by outlines some potential future therapies for Graves' disease and Graves' Ophthalmopathy. These include:

Immunotherapy

Rituximab

Graves' disease is characterized by autoantibodies against the TSH receptor. These are synthesized by B-cells which infiltrate the thyroid. Immature B-lymphocytes as well as activated mature B-lymphocytes are known to express CD20 (an activated-glycosylated phosphoprotein) on their cell surface. The drug Rituximab is a monoclonal antibody which targets this CD 20 complex. As such, researchers are looking at whether it can modulate the reaction of B-cells in Graves' disease patients.

An article by t reviewed the findings of 5 papers (written by 3 different research groups) on the use of rituximab in Graves' disease. Unfortunately, the results did not show a significant improvement with the use of rituximab. The results were also difficult to interpret as patients were often treated with methimazole at the same time, and some were hyperthyroid, while others were euthyroid at the time of treatment.

Interestingly, the effect on Graves' ophthalmopathy (GO) turned out differently. Patients in the above studies who had GO showed improvement in their clinical activity score (CAS) and proptosis even when thyroid function was unaffected. Rituximab even worked on patients who did not respond to or relapsed after glucocorticoid treatment. More studies are needed to further define a possible role for rituximab in the treatment of GD and GO.

CFZ533

According to , a Phase 2 trial of the biological agent CFZ533 is underway. "This agent is an Fc-silenced fully human anti-human CD40 monoclonal antibody, incapable of B cell depletion but a potent inhibitor of CD40 pathway activation. By affecting CD40–CD154 interactions that occur between antigen-presenting cells and T-cells, it is presumed to modulate humoral immunity, germinal center formation, affinity maturation and memory B cell development." According to , the trial is an open label study to evaluate the safety and efficacy of CFZ533 following 12 weeks treatment in patients with Graves' disease. The results of the study have not yet been released.

ATX-GD-59

ATX-GD-59 is the result of a British and Belgium joint commercial venture called Apitope. According to a company , Apitope uses a "proprietary discovery platform to select and develop highly specific peptide-based therapeutics, known as "apitopes" (antigen processing independent epitopes), that directly target the immunological basis of autoimmune diseases." They go on to say: "While current therapies for autoimmune diseases typically have the effect of suppressing the immune system, apitopes modulate only the malfunctioning part of the immune system in order to avoid such global immune suppression." with ATX-GD-59 are underway.

Ultrasound-based therapies

High-intensity focused ultrasound (HIFU)

High-intensity focused ultrasound is a non-invasive therapeutic technique that uses non-ionizing ultrasonic waves to heat tissue. It has been used in treating benign thyroid nodules (. also used ultrasound-guided HIFU in the treatment of 30 patents with persistent or relapsed GD. After 1 year, 8 patients (26.7%) had experienced a relapse. Baseline TSHr were significantly decreased at 6- and 12-months post-treatment.

Radiofrequency ablation

Radiofrequency ablation (RFA) is a percutaneous treatment (usually performed with ultrasound guidance) that results in thermal tissue necrosis and fibrosis, leading to shrinkage. It has been successfully used in the treatment of large thyroid nodules (TNs) and in toxic adenomas. (2009) found that thyroid nodules and related symptoms were stably controlled for 2 years in their study of 94 elderly patients with thyroid nodules. Sixty-six of them had nontoxic goiter and 28 had toxic or pre-toxic goiter. Compressive symptoms improved in all patients and completely disappeared in 83 of 94 (88%) patients. Hyperthyroidism resolved in most patients allowing methimazole therapy to be completely withdrawn in 79% of patients with pre-toxic and toxic TNs. The treatment was well tolerated by all patients. Expansion of this treatment to patients with GD has not yet been undertaken.

In conclusion, we wish all the best to Ms.Williams while she undergoes treatment and recovery from her condition.

Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.