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

of 131 I therapy and only resumed 3 days after 131 I (Walter et al., 2007).
If the anti-thyroid drug cannot be discontinued, the effect can be overcome
by adjusting to a higher radioiodine dose.
Course of Disease. The course of hyperthyroidism in a patient who
has received an optimal dose of 131 I is characterized by progressive
recovery. Beginning a few weeks after treatment, the symptoms of
hyperthyroidism gradually abate over a period of 2-3 months. If therapy
has been inadequate, the necessity for further treatment is apparent
within 6-12 months. It is not uncommon, however, for the serum
TSH to remain low for several months after 131 I therapy, especially
if the patient was not rendered euthyroid before receiving the
radioactive iodine. Occasionally, this delayed recovery of the hypothalamic-pituitary-thyroid
axis results in a picture of central hypothyroidism,
with low circulating thyroid hormones. Thus, assessing
radioactive iodine failure based on TSH concentrations alone may be
misleading and should always be accompanied by determination of
free T 4
and usually serum T 3
concentrations. Furthermore, transient
hypothyroidism, lasting up to 6 months, may occur in up to 50% of
patients receiving a dose of 131 I calculated to result in euthyroidism
(Aizawa et al., 1997). This is less of a problem if the patient receives
a higher, ablative dose of 131 I because hypothyroidism occurs far
more frequently and persists.
Depending to some extent on the dosage schedule adopted,
80% of patients are cured by a single dose, ~20% require two doses,
and a very small fraction require three or more doses before the disorder
is controlled. Patients treated with larger doses of 131 I almost
always develop hypothyroidism within a few months.
β Adrenergic antagonists, anti-thyroid drugs, or both, or stable
iodide, can be used to hasten the control of hyperthyroidism
while awaiting the full effects of the radioactive iodine.
Advantages. The advantages of radioactive iodine in the
treatment of Graves’ disease are many. No death as a
direct result of the use of the isotope has been reported.
There have been reports of increased mortality from cardiovascular
and cerebrovascular disease in the first year
after radioactive iodine therapy (Franklyn et al., 1998);
however, there is no evidence that the increased mortality
was related to the radioactive iodine itself, and longterm
follow-up of radioactive iodine therapy for Graves’
disease has demonstrated no increase in overall cancer
mortality in patients treated with 131 I (Ron et al., 1998).
In the non-pregnant patient, no tissue other than the thyroid
is exposed to sufficient ionizing radiation to be
detectably altered. Nevertheless, continuing concern
about potential effects of radiation on germ cells
prompts some endocrinologists to advocate anti-thyroid
drugs or surgery in younger patients who are acceptable
operative risks. Hypoparathyroidism is a small risk of
surgery. With radioactive iodine treatment, the patient is
spared the risks and discomfort of surgery. The cost is
low, hospitalization is not required in the U.S., and
patients can participate in their customary activities during
the entire procedure, although there are recommendations
to limit exposure to young children.
Disadvantages. The chief consequence of the use of
radioactive iodine is the high incidence of delayed
hypothyroidism. Even when elaborate procedures are
used to estimate iodine uptake and gland size, most
patients become hypothyroid.
Several analyses of groups of patients treated ≥10 years previously
suggest that the eventual rate may exceed 80%. However, it
now appears that the incidence of hypothyroidism also increases progressively
after subtotal thyroidectomy or after anti-thyroid drug
therapy, and such failure of glandular function is probably part of
the natural progression of Graves’ disease, no matter what the therapy.
Although cancer death rate is not increased after radioiodine
therapy, there is a small but significant increase shown in specific
types of cancer, including stomach, kidney, and breast (Metso et al.,
2007). This finding is especially significant because these tissues all
express the iodine transporter NIS and may be especially susceptible
to radiation effects.
It is essential that patients treated with radioiodine understand
that the resulting hypothyroidism will require lifelong treatment and
monitoring. Because there are variations in the interval of time from
treatment to the development of hypothyroidism, patients must have
regular thyroid function testing after radioiodine. Also, once diagnosed,
it is difficult to ensure that patients who need the hormone
actually take it. Because the health risks of untreated subclinical
hypothyroidism are becoming increasingly evident (Biondi and
Cooper, 2008), hypothyroidism, either subclinical or overt, requires
long-term follow-up to ensure adequate thyroid hormone status and
optimal replacement therapy.
Another disadvantage of radioactive iodine therapy is the
long period of time that is sometimes required before the hyperthyroidism
is controlled. When a single dose is effective, the response
is most satisfactory; however, when multiple doses are needed, it
may be many months or a year or more before the patient is well.
This disadvantage can be largely overcome if the initial dose is sufficiently
large. Other disadvantages include possible worsening of
ophthalmopathy after treatment (Bartalena et al., 1998a).
Radioactive iodine treatment can induce a radiation thyroiditis, with
release of preformed thyroxine and triiodothyronine into the circulation.
In most patients, this is asymptomatic, but in some there can
be worsening of symptoms of hyperthyroidism and rarely cardiac
manifestations, such as atrial fibrillation or ischemic heart disease
and very rarely thyroid storm. Pretreatment with anti-thyroid drugs
should reduce or eliminate this complication and is indicated especially
in those with underlying cardiac disease or the elderly. Finally,
salivary gland dysfunction may be seen, especially after the higher
doses used for the treatment of thyroid cancer (Mandel and Mandel,
2003). Sialogogic agents to hasten the transit of radioiodine through
the salivary glands are used by many clinicians but have unproven
efficacy. Salivary gland damage is most strongly linked to the cumulative
dose of radioiodine.
Indications. The clearest indication for this form of
treatment is hyperthyroidism in older patients and in
those with heart disease. Radioactive iodine also is the
best form of treatment when Graves’ disease has persisted
or recurred after subtotal thyroidectomy and
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CHAPTER 39
THYROID AND ANTI-THYROID DRUGS