The study, led by Paul Ladenson, M.D., director of the Division of Endocrinology at The Johns Hopkins University School of Medicine, and Furio Pacini at the University of Siena in Italy, was reported in the December online edition of the Journal of Clinical Endocrinology and Metabolism.
Typically, radioiodine treatment for cancer of the thyroid gland requires temporary discontinuation of thyroid hormone replacement for several weeks, leading to weight gain, constipation, fatigue, slowed thinking, depressed mood, muscle cramps, intolerance of cold temperatures and other symptoms. "This study shows that patients who use a recombinant form of TSH can continue their thyroid replacement therapy and enjoy a better quality of life during their cancer treatment," Ladenson says.
Thyroid cancer is first treated by surgical removal of the gland in the neck, often followed by radioactive iodine treatment to remove any remaining thyroid tissue.
Once the thyroid is diseased or removed, it no longer produces the hormones T4 (thyroxine) and T3 (triiodothyronine), which help regulate heart rate, blood pressure, body temperature and weight. Therefore, it is essential to add back the thyroid hormone L-thyroxine to keep the body functioning normally. Paradoxically, for radioiodine treatment to be effective, thyroid hormone treatments previously had to be suspended, according to Ladenson. Suspending hormone treatments stimulates the pituitary gland to produce thyroid-stimulating hormone (TSH). TSH stimulates any remaining thyroid tissue to concentrate the radioiodine, which can then eliminate remaining thyroid tissue. Once inside the cell, radioiodine emits beta particles that damage the DNA in thyroid cells without affecting surrounding tissues, according to Ladenson.
TSH made by the pituitary gland and rhTSH produce equivalent biological actions, according to Ladenson, and there are only slight structural differences.
"This multi-institutional study proved that rhTSH is just as effective as the TSH produced by the body in destroying these remaining thyroid cells," Ladenson says.
This randomized, controlled, study involved 60 patients from four centers in Europe and five in North America. The first patient was enrolled on Dec. 17, 2001, and the last patient completed the final study visit on Sept. 26, 2003.
Within 14 days after surgical removal of the thyroid, 32 of these patients were randomized to a group that received their thyroid hormone treatment, L-thyroxine, without interruption and rhTSH for four to six weeks prior to radioiodine treatment. Twenty-eight were randomized to a group that did not receive L-thyroxine or rhTSH and were then treated after hypothyroidism prompted their own pituitary glands to make TSH. Quality of life was tested during this period and symptoms were assessed using the Billewicz scale -- an observer-rated evaluation of 14 symptoms and signs exhibited by patients who have a lack of thyroid hormone in their system. Patients then underwent radioiodine treatment. Eight months after this treatment, doctors performed a scan to determine if there was any remaining thyroid tissue.
Before radioiodine treatment, Billewicz scores revealed both groups to be comparable -- with mild and transient symptoms reported by only eight patients in each group. As they were prepared for radioiodine treatment, the group denied thyroid hormone therapy had significantly higher total symptom scores at weeks two and four. The most common complaints of patients who were denied thyroid hormone therapy, vs. patients who received thyroid hormone therapy and rhTSH, were cold intolerance (50 percent vs. 21 percent), weight increase (60 percent vs. 21 percent), constipation (43 percent vs. 3 percent), lethargy (50 percent vs. 12 percent), cold skin (47 percent vs. 12 percent), and puffiness around the eyes (50 percent vs. 0 percent).
Eight months after radioiodine therapy, tests showed that remaining thyroid cells had been successfully destroyed in all patients in both groups, according to the study.
These results clearly indicate that rhTSH combined with radiation therapy successfully destroys remaining thyroid tissue without the need to discontinue thyroid hormones, thus reducing the unpleasant side effects generally associated with this treatment, Ladenson says.