A multicenter international study has found that after
surgery for thyroid cancer, giving genetically engineered
human thyroid-stimulating hormone, or rhTSH, before
radioiodine treatment avoids the previous need to stop
thyroid replacement therapy and the miserable side effects
that go with it.
The study, led by Paul Ladenson, director of the
Division of
Endocrinology at the Johns Hopkins 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 said.
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, Ladenson said.
Suspending hormone treatments stimulates the pituitary
gland to produce thyroid-stimulating hormone; 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, and there are only slight
structural differences, he said.
"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
said.
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 the 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, the study
reported.
These results, Ladenson said, 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.