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 I. Sherman, assistant professor of endocrine neoplasia,
and Madeleine Duvic, professor of dermatology, both in M. D.
Andersons Department of Internal Medical Specialties,
demonstrated that targretin, an RXR retinoid compound, causes
hypothyroidism. This discovery also revealed a previously unknown
genetic mechanism in the pituitary gland.
The findings were published in the April 8th issue of The New
England Journal of Medicine.
Thyroid-Stimulating Hormone Synthesis Inhibited
Targretin acts by inhibiting the pituitary gland's synthesis of the
thyroid-stimulating hormone necessary for normal thyroid hormone
production, said Dr. Sherman. The finding gives endocrinologists a
better understanding of how the pituitary gland 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, said 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 said the discovery may have an immediate impact on the
treatment and outcome of two rare thyroid diseases for which current
treatment is often unsuccessful. Both diseases, thyroid-stimulating
hormonesecreting pituitary adenomas and isolated pituitary
resistance to thyroid hormones, cause unusual forms of
hyperthyroidism due to pituitary stimulation of the thyroid gland.
Sweaters in Houston in August
The discovery was a result of a phase III clinical trial of targretin
as a treatment for cutaneous T-cell lymphoma that is currently being
conducted at M. D. Anderson. During the course of the study, Dr.
Duvic noted that after a few treatments of targretin, 95% of patients
developed hypothyroidism. 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.
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, said 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, said 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 higher for women,
said Dr. Sherman.
The original study using targretin to treat skin cancer is ongoing.
Targretin has also been used in studies as a treatment for other
cancers, such as breast, lung, and head and neck cancers. Although
hypothyroidism occurred in patients with cutaneous T-cell lymphoma,
patients with other cancers may be less susceptible to this effect of targretin.