New Genetic Mechanism Associated With Thyroid Diseases

In the course of a cancer-related study, researchers at The University of Texas M. D. Anderson Cancer Center stumbled upon an important genetic mechanism that may help in the treatment of two rare thyroid diseases.

Drs. Steven Sherman, assistant professor of endocrine neoplasia, and Madeleine Duvic, professor of dermatology, both in M. D. Anderson's department of internal medical specialties, successfully demonstrated that targretin, an RXR retinoid compound, causes hypothyroidism. This discovery also revealed a genetic mechanism in the pituitary gland not previously known.

The findings were published in the April 8th issue of the New England Journal of Medicine.

Targretin acts by inhibiting the pituitary's synthesis of the thyroid-stimulating hormone necessary for normal thyroid hormone production, explains Dr. Sherman. The finding gives endocrinologists a better understanding of how the pituitary gland - located in the brain - is regulated.

"Hypothyroidism is a serious condition that is easily treated and resolved. What was important was the discovery of the mechanism by which the pituitary is regulated," says Dr. Sherman. "This was a case of going where your data leads you and coming up with an unexpected finding. It opens up a whole new area of investigation."

Dr. Sherman says the discovery may immediately impact treatment and outcomes for two rare thyroid diseases for which current treatment is often unsuccessful. Both diseases cause unusual forms of hyperthyroidism due to pituitary stimulation of the thyroid gland.

The discovery was a result of a phase 3 clinical trial of targretin, currently under investigation at M. D. Anderson as a treatment for cutaneous T-cell lymphoma (CTCL).

Dr. Duvic noted that after a few treatments of targretin, 96 percent of patients developed hypothyroidism, a condition resulting from a slowdown in thyroid activity.

The patients, who prior to ingesting targretin showed no signs of the condition, began to experience fatigue, memory loss, depression and a heightened sensitivity to cold, symptoms commonly associated with hypothyroidism.

"All of the patients were severely fatigued, but even more surprising, most were so cold they were wearing sweaters and turning off their air conditioners in Houston, in August," says Dr. Duvic.

Intrigued by the consistent development of this side effect, Dr. Duvic referred her patients to Dr. Sherman.

"Because the pituitary, sometimes called the master gland, acts like a thermostat," says Dr. Sherman, "a malfunction in the pituitary affects the thyroid, which can disrupt the metabolism and specific functions of organs throughout the body."

An estimated 10 million Americans are affected by thyroid-related diseases, and the incidence is disproportionately high for women, Dr. Sherman added.

- KATHRYN WILEY

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©2006 Texas Medical Center

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