DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1156 when prolonged treatment with anti-thyroid drugs has
not led to remission. Finally, radioactive iodine is indicated
in patients with toxic nodular goiter because the
disease does not go into spontaneous remission.
thyroid hormone can be evaluated in this way.
Following the administration of a tracer dose, the pattern
of localization in the thyroid gland can be depicted
by a special scanning apparatus, and this technique is
sometimes useful in defining thyroid nodules as functional
(“hot”) or non-functional (“cold”) and in finding
ectopic thyroid tissue and occasionally metastatic thyroid
tumors.
SECTION V
HORMONES AND HORMONE ANTAGONISTS
The risk of inducing hypothyroidism is less in nodular goiter
than in Graves’ disease, perhaps because of the normal progression
of the latter and the preservation of nonautonomous thyroid
tissue in the former. Usually, larger doses of radioactive iodine are
required in the treatment of toxic nodular goiter than in the treatment
of Graves’ disease. Radioactive iodine has been used to
decrease the size of large nontoxic multinodular goiters that are
causing compressive symptoms in patients who are otherwise poor
operative risks. Although surgery remains the treatment of choice
for patients with compressive multinodular goiters, radioactive
iodine therapy may benefit elderly patients, especially those with
cardiopulmonary disease. The uptake in multinodular goiters may
be low, so some have increased radioiodine uptake by administration
of exogenous recombinant human TSH (thyrotropin alfa
[THYROGEN]) (Duntas and Cooper, 2008), but caution should be
exercised because this treatment may induce transient elevations in
serum thyroxine and triiodothyronine that could result in excessive
stimulation of the heart.
Contraindications. The main contraindication for the use of 131 I therapy
is pregnancy. After the first trimester, the fetal thyroid will concentrate
the isotope and thus suffer damage; even during the first
trimester, radioactive iodine is best avoided because there may be
adverse effects of radiation on fetal tissues. The risk of causing neoplastic
changes in the thyroid gland has been an ongoing concern
since radioactive iodine was first introduced, and only small numbers
of children have been treated in this way. Indeed, many clinics have
declined to treat younger patients for fear of causing cancer and have
reserved radioactive iodine for patients older than some arbitrary
age, such as 25 or 30 years. Because experience with 131 I is now vast,
these age limits are lower than they were in the past. The most recent
report by the Cooperative Thyrotoxicosis Therapy Follow-up Study
Group shows no increase in total cancer mortality following 131 I
treatment for Graves’ disease (Ron et al., 1998). Furthermore, there
was no increase in the occurrence of leukemia following large-dose
131
I therapy for thyroid cancer, although there was an increase in colorectal
cancers in this population (de Vathaire et al., 1997). These
data strongly suggest that laxatives be given to all patients receiving
131
I therapy for treatment of thyroid cancer to decrease the risk of
future digestive tract malignancies. Transient abnormalities in testicular
function have been reported following 131 I therapy for treatment
of thyroid cancer, but no long-term effects on fertility in either men
or women have been demonstrated (Dottorini et al., 1995; Pacini et
al., 1994). Patients with allergies to iodine contrast agents or to topical
iodide-containing products should not have any adverse reaction
to 131 I. The amount of elemental iodine contained in the
treatment is not greater than that contained in iodized salt or flour
that is part of regular dietary intake.
Diagnostic Uses. Measurement of the thyroidal accumulation
of a tracer dose is helpful in the differential
diagnosis of hyperthyroidism and nodular goiter. The
response of the thyroid to TSH-suppressive doses of
Thyroid Carcinoma. Because most well-differentiated thyroid carcinomas
accumulate very little iodine, stimulation of iodine uptake
with TSH is required to treat metastases effectively. Currently,
endogenous TSH stimulation is evoked by withdrawal of thyroid
hormone replacement therapy in patients previously treated with
near-total thyroidectomy with or without radioactive ablation of
residual thyroid tissue. Total-body 131 I scanning and measurement
of serum thyroglobulin when the patient is hypothyroid (TSH
>35 mU/L) help to identify metastatic disease or residual thyroid
bed tissue. Depending on the residual uptake or the presence of
metastatic disease, an ablative dose of 131 I ranging from 30 mCi to
>150 mCi is administered, and a repeat total body scan is obtained
1 week later. The precise amount of 131 I needed to treat residual
tissue and metastases is controversial. Thyrotropin alfa (recombinant
human TSH) is now available to test the ability of thyroid tissue,
both normal and malignant, to take up radioactive iodine and
to secrete thyroglobulin (Haugen et al., 1999). Thyrogen allows
assessment of the presence of metastatic disease, without the
necessity for patients to stop their suppressive levothyroxine therapy
and become clinically hypothyroid. Thyrotropin alfa is
approved for diagnostic scanning and for thyroid remnant ablation
after thyroidectomy in thyroid cancer patients, but not for treatment
of metastatic disease. (Duntas and Cooper, 2008; Pacini and
Castangna, 2008).
TSH-suppressive therapy with levothyroxine is indicated in
all patients after treatment for thyroid cancer. The goal of therapy
usually is to keep serum TSH levels in the subnormal range, although
relaxing the degree and duration of suppression, especially for stage
1 and 2 cancers, is now recommended (Burmeister et al., 1992;
Cooper et al., 2006). Follow-up evaluation every 6 months is reasonable,
along with determination of serum thyroglobulin concentrations
(Spencer and LoPresti, 2008). Patients with a rise in
thyroglobulin but no detectable disease on whole-body scan require
additional imaging and consideration of alternative treatments
including surgery and external radiation (Kloos, 2008). A rise in
serum thyroglobulin concentration is often the first indication of
recurrent disease. The prognosis in patients with thyroid cancer
depends on the pathology and size of the tumor and is generally
worse in older individuals. Overall, the vast majority of patients with
thyroid cancer will not die of their disease. Papillary cancer is usually
not aggressive; the 10-year survival rate exceeds 80%. Follicular
cancer is more aggressive and can metastasize via the bloodstream.
Still, prognosis is fair and long-term survival is common. Even in
patients with metastatic, differentiated thyroid cancer, 131 I therapy
is very effective and may be even curative (Cooper et al., 2006).
Anaplastic cancer is the exception: It is highly malignant with survival
usually <1 year. Medullary thyroid carcinomas do not accumulate
I – and cannot be treated with 131 I.