Page 712 - Basic _ Clinical Pharmacology ( PDFDrive )

698 SECTION VII Endocrine Drugs

levothyroxine therapy may be necessary even after discontinuance when the patient becomes clinically euthyroid. However, mild
because of amiodarone’s very long half-life. to moderately severe thyrotoxicosis can often be controlled with
methimazole given in a single morning dose of 20–40 mg initially
HYPERTHYROIDISM for 4–8 weeks to normalize hormone levels. Maintenance therapy
requires 5–15 mg once daily. Alternatively, therapy is started
Hyperthyroidism (thyrotoxicosis) is the clinical syndrome that with propylthiouracil, 100–150 mg every 6 or 8 hours until the
results when tissues are exposed to high levels of thyroid hormone patient is euthyroid, followed by gradual reduction of the dose to
(Table 38–4). the maintenance level of 50–150 mg once daily. In addition to
inhibiting iodine organification, propylthiouracil also inhibits the
GRAVES’ DISEASE conversion of T to T , so it brings the level of activated thyroid
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hormone down more quickly than does methimazole. The best
clinical guide to remission is reduction in the size of the goiter.
The most common form of hyperthyroidism is Graves’ disease, or Laboratory tests most useful in monitoring the course of therapy
diffuse toxic goiter. The presenting signs and symptoms of Graves’ are serum FT , FT , and TSH levels.
disease are set forth in Table 38–4. 3 4
Reactions to antithyroid drugs have been described above.
A minor rash can often be controlled by antihistamine therapy.
Pathophysiology Because the more severe reaction of agranulocytosis is often her-
Graves’ disease is considered to be an autoimmune disorder in alded by sore throat or high fever, patients receiving antithyroid
which a defect in suppressor T lymphocytes stimulates B lym- drugs must be instructed to discontinue the drug and seek imme-
phocytes to synthesize antibodies (TSH-R Ab [stim]) to thyroidal diate medical attention if these symptoms develop. White cell and
antigens. The TSH-R Ab [stim] is directed against the TSH differential counts and a throat culture are indicated in such cases,
receptor in the thyroid cell membrane and stimulates growth and followed by appropriate antibiotic therapy. Treatment should also
biosynthetic activity of the thyroid cell. Genetics, the postpartum be stopped if significant elevations in transaminases (two to three
state, cigarette smoking, and physical and emotional stress increase times the upper limit of normal) occur.
TSH-R Ab [stim] development. A genetic predisposition is shown
by a high frequency of HLA-B8 and HLA-DR3 in Caucasians, B. Thyroidectomy
HLA-Bw46 and HLA-B5 in Chinese, and HLA-B17 in African A near-total thyroidectomy is the treatment of choice for patients
Americans. Spontaneous remission occurs but some patients with very large glands or multinodular goiters. Patients are treated
require years of antithyroid therapy. with antithyroid drugs until euthyroid (about 6 weeks). In addi-
tion, for 10–14 days prior to surgery, they receive saturated
Laboratory Diagnosis solution of potassium iodide, 5 drops twice daily, to diminish
vascularity of the gland and simplify surgery. About 80–90% of
In most patients with hyperthyroidism, T , T , FT , and FT are patients will require thyroid supplementation following near-total
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elevated and TSH is suppressed (Table 38–2). Radioiodine uptake thyroidectomy.
is usually markedly elevated as well. Antithyroglobulin, thyroid
peroxidase, and TSH-R Ab [stim] antibodies are usually present. C. Radioactive Iodine
Management of Graves’ Disease Radioiodine therapy (RAI) utilizing 131 I is the preferred treat-
ment for most patients over 21 years of age. In patients without
The three primary methods for controlling hyperthyroidism are heart disease, the therapeutic dose may be given immediately in
antithyroid drug therapy, destruction of the gland with radioactive a range of 80–120 μCi/g of estimated thyroid weight corrected
iodine, and surgical thyroidectomy. None of these methods alters for uptake. In patients with underlying heart disease or severe
the underlying pathogenesis of the disease. thyrotoxicosis and in elderly patients, it is desirable to treat with
antithyroid drugs (preferably methimazole) until the patient is
A. Antithyroid Drug Therapy euthyroid. The medication is stopped for 2 to 3 days before RAI
Drug therapy is most useful in young patients with small glands is administered so as not to interfere with RAI retention but
and mild disease. Methimazole (preferred) or propylthiouracil can be restarted 3–5 days later, and then gradually tapered over
is administered until the disease undergoes spontaneous remis- 4–6 weeks as thyroid function normalizes. Iodides should be
131
sion. This is the only therapy that leaves an intact thyroid gland, avoided to ensure maximal I uptake. Six to 12 weeks following
but it does require a long period of treatment and observation the administration of RAI, the gland will shrink in size and the
(12–18 months), and there is a 50–60% incidence of relapse. patient will usually become euthyroid or hypothyroid. A second
Methimazole is preferable to propylthiouracil (except in preg- dose may be required if there is minimal response 3 months post-
nancy and thyroid storm) because it has a lower risk of serious liver RAI. Hypothyroidism occurs in about 80% of patients following
injury and can be administered once daily, which may improve RAI. Serum FT and TSH levels should be monitored regularly.
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adherence. Antithyroid drug therapy is usually begun with divided When hypothyroidism develops, prompt replacement with oral
doses, shifting to maintenance therapy with single daily doses levothyroxine, 50–150 mcg daily, should be instituted.