In Graves' disease, the thyroid gland never stops. Thyroid-stimulating antibodies bind to receptors, activating them to keep the thyroid hormone coming and coming -- like a broken traffic light stuck on green -- and causing the body problems in regulating energy, controlling other hormones and maintaining cells throughout the body.
Graves' disease causes the body's immune system to act against the body's own cells and organs. It typically first occurs in people under the age of 40 and affects approximately 1 percent of the U.S. population, with women five to 10 times more likely than men to have it.
Lead researcher Susanne Neumann, Ph.D., and her colleagues at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) have identified a chemical compound that binds to the receptors and acts as an antagonist, keeping the thyroid-stimulating antibodies from their work, potentially allowing the thyroid cells to revert to normal function.
Though treatments are currently available for hyperthyroidism caused by Graves' disease, including surgery, radioactive iodine, and antithyroid drugs, the relapse rates for these treatments are 5 percent, 21 percent and 40 percent, respectively, and each comes with unfavorable side effects.
"Our goal is to develop an easily produced, orally administered, safe and effective drug with few to no side effects that can be used in place of some of the more invasive treatments of hyperthyroidism caused by Graves' disease," said Marvin Gershengorn, M.D., chief of the Laboratory of Endocrinology and Receptor Biology within NIDDK's intramural research program and the senior author on the paper.
The newly discovered compound may have the added benefit of helping those with eye problems caused by Graves' disease -- called Graves' ophthalmopathy -- experienced by more than 25 percent of people with the disease.
Eye problems may include painful swelling in the eye sockets, double vision, tears or itchy eyes, and protruding eyes with swollen eyelids that can't be easily shut, increasing the risk for eye diseases.
Because the swelling in the eyes is thought to be associated with the same overstimulation of receptors caused by the same thyroid-stimulating antibodies as in the thyroid, the potential thyroid treatment may have the added benefit of treating the eye problems as well.
While this is good news for those suffering from Graves' disease, patients will have to wait a little longer while further testing is done, as the antagonist has not yet been tested in animals or people and still has multiple steps of toxicology and safety testing before it may be ready for human trials.
The Gershengorn team's research isn't just limited to Graves' disease. They're hoping to tackle thyroid cancer as well.
By researching the thyroid-stimulating hormone receptor, they're hoping to use drug-like compounds to stimulate this receptor to treat people with thyroid cancer, who need more stimulation of thyroid cancer cells to increase the efficacy of iodine radiation.
They've tested their discovery in mice and hope to perform pre-clinical studies and to develop human trials in the foreseeable future.
The findings are published this month in the Journal of Clinical Endocrinology and Metabolism.
