Hyperthyroidism is the second most prevalent endocrine disor-der, after diabetes mellitus. Graves’ disease, the most common type of hyperthyroidism, results from an excessive output of thy-roid hormones caused by abnormal stimulation of the thyroid gland by circulating immunoglobulins. It affects women eight times more frequently than men, with onset usually between the second and fourth decades (Tierney et al., 2001). It may appear after an emotional shock, stress, or an infection, but the exact sig-nificance of these relationships is not understood. Other common causes of hyperthyroidism include thyroiditis and excessive in-gestion of thyroid hormone.
Patients with well-developed hyperthyroidism exhibit a charac-teristic group of signs and symptoms (sometimes referred to as thyrotoxicosis). The presenting symptom is often nervousness.These patients are often emotionally hyperexcitable, irritable, and apprehensive; they cannot sit quietly; they suffer from pal-pitations; and their pulse is abnormally rapid at rest as well as on exertion. They tolerate heat poorly and perspire unusually freely. The skin is flushed continuously, with a characteristic salmon color, and is likely to be warm, soft, and moist. Elderly patients, however, may report dry skin and diffuse pruritus. A fine tremor of the hands may be observed. Patients may exhibit exophthalmos (bulging eyes), which produces a startled facialexpression.
Other manifestations include an increased appetite and di-etary intake, progressive weight loss, abnormal muscular fatiga-bility and weakness (difficulty in climbing stairs and rising from a chair), amenorrhea, and changes in bowel function. The pulse rate ranges constantly between 90 and 160 beats/min; the sys-tolic, but characteristically not the diastolic, blood pressure is elevated; atrial fibrillation may occur; and cardiac decompen-sation in the form of heart failure is common, especially in el-derly patients. Osteoporosis and fracture are also associated with hyperthyroidism.
Cardiac effects may include sinus tachycardia or dysrhyth-mias, increased pulse pressure, and palpitations; it has been sug-gested that these changes may be related to increased sensitivity to catecholamines or to changes in neurotransmitter turnover. Myocardial hypertrophy and heart failure may occur if the hyper-thyroidism is severe and untreated.
The course of the disease may be mild, characterized by re-missions and exacerbations and terminating with spontaneous re-covery in a few months or years. Conversely, it may progress relentlessly, with the untreated person becoming emaciated, in-tensely nervous, delirious, and even disoriented; eventually, the heart fails.
Symptoms of hyperthyroidism may occur with the release of excessive amounts of thyroid hormone as a result of inflamma-tion after irradiation of the thyroid or destruction of thyroid tis-sue by tumor. Such symptoms may also occur with excessive administration of thyroid hormone for treatment of hypothy-roidism. Long-standing use of thyroid hormone in the absence of close monitoring may be a cause of symptoms of hyperthy-roidism. It is also likely to result in premature osteoporosis, par-ticularly in women.
The thyroid gland invariably is enlarged to some extent. It is soft and may pulsate; a thrill often can be palpated, and a bruit is heard over the thyroid arteries. These are signs of greatly in-creased blood flow through the thyroid gland. In advanced cases, the diagnosis is made on the basis of the symptoms and an in-crease in serum T4 and an increased 123I or 125I uptake by the thy-roid in excess of 50%.
Although hyperthyroidism is much less common in elderly peo-ple than hypothyroidism, patients older than 60 years account for 10% to 15% of the cases of thyrotoxicosis. Although some older patients develop typical signs and symptoms of thyrotoxicosis, in most an atypical picture is present, which is often subclinical (Toft, 2001).
Elderly patients commonly present with vague and nonspecific signs and symptoms, making disorders hard to detect. Symptoms such as tachycardia, fatigue, mental confusion, weight loss, change in bowel habits, and depression can be attributed to age and other illnesses common to elderly people. In addition, the patient may report cardiovascular symptoms and difficulty climbing stairs or rising from a chair because of muscle weakness. New or worsen-ing heart failure or angina is more likely to occur in elderly than in younger patients. The elderly patient may experience a single man-ifestation, such as atrial fibrillation, anorexia, or weight loss. These signs and symptoms may mask the underlying thyroid disease.
Spontaneous remission of hyperthyroidism is rare in elderly patients. Measurement of TSH is indicated in elderly patients with unexplained physical or mental deterioration.
Treatment of hyperthyroidism is directed toward reducing thy-roid hyperactivity to relieve symptoms and remove the cause of important complications. Treatment depends on the cause of the hyperthyroidism and may require a combination of therapeutic approaches.
Two forms of pharmacotherapy are available for treating hyper-thyroidism and controlling excessive thyroid activity: (1) use of irradiation by administration of the radioisotope 123I or 131I for destructive effects on the thyroid gland and (2) antithyroid med-ications that interfere with the synthesis of thyroid hormones and other agents that control manifestations of hyperthyroidism. Sur-gical removal of most of the thyroid gland is a nonpharmacologic alternative.
The goal of radioactive iodine ther-apy (123I or 131I) is to destroy the overactive thyroid cells. Use of radioactive iodine is the most common treatment in elderly pa-tients. Almost all the iodine that enters and is retained in the body becomes concentrated in the thyroid gland. Therefore, the radio-active isotope of iodine is concentrated in the thyroid gland, where it destroys thyroid cells without jeopardizing other radiosensitive tissues. Over a period of several weeks, thyroid cells exposed to the radioactive iodine are destroyed, resulting in reduction of the hyperthyroid state and inevitably hypothyroidism.
The patient is instructed about what to expect with this taste-less, colorless radioiodine, which may be administered by the radi-ologist. A single oral dose of the agent is administered, based on 80 to 160 μCi/g estimated thyroid weight. About 70% to 85% of pa-tients are cured by one dose of radioactive iodine. An additional 10% to 20% require two doses; rarely is a third dose necessary. Use of an ablative dose of radioactive iodine initially causes an acute re-lease of thyroid hormone from the thyroid gland and may cause an increase of symptoms. The patient is observed for signs of thyroidstorm; propranolol is useful in controlling these symptoms.
After treatment with radioactive iodine, the patient is followed closely until the euthyroid state is reached. In 3 to 4 weeks, symptoms of hyperthyroidism subside. Because the incidence of hypo-thyroidism after this form of treatment is very high (ie, more than 90% at 10 years), close follow-up is required to evaluate thyroid function. Thyroid hormone replacement is necessary; small doses are usually prescribed, with the dose gradually increased over a period of months (up to about 1 year) until the FT4 and TSH lev-els stabilize within normal ranges.
Radioactive iodine has been used to treat toxic adenomas and multinodular goiter and most varieties of thyrotoxicosis (rarely per-manently successful); it is preferred for treating patients beyond the childbearing years with diffuse toxic goiter. It is contraindicated in pregnancy and in nursing mothers because radioiodine crosses the placenta and is secreted in breast milk. A major advantage of treat-ment with radioactive iodine is that it avoids many of the side ef-fects associated with antithyroid medications. However, many patients and their families fear medications that are radioactive. Be-cause of this fear, many patients elect to take antithyroid medica-tions rather than radioactive iodine.
The use of radioactive iodine is generally recommended for treatment of thyrotoxicosis in elderly patients unless an enlarged thyroid gland is pressing on the airway. The hypermetabolic state of thyrotoxicosis must be controlled by antithyroid medications before radioactive iodine is administered because radiation may precipitate thyroid storm by increasing the release of hormone from the thyroid gland. Thyroid storm, if it occurs, has a mortal-ity rate of 10% in elderly patients (Chart 42-4).
The objective of pharmacotherapy is toinhibit one or more stages in thyroid hormone synthesis or hor-mone release; another goal may be to reduce the amount of thy-roid tissue, with resulting decreased thyroid hormone production.
Antithyroid agents block the utilization of iodine by inter-fering with the iodination of thyrosine and the coupling of iodothyrosines in the synthesis of thyroid hormones. This pre-vents the synthesis of thyroid hormone. The most commonly used medications are propylthiouracil (Propacil, PTU) or me-thimazole (Tapazole) until the patient is euthyroid (ie, neither hyperthyroid nor hypothyroid). These medications block ex-trathyroidal conversion of T4 to T3. Because antithyroid med-ications do not interfere with release or activity of previously formed thyroid hormones, it may take several weeks for relief of symptoms. At this time the maintenance dose is established, fol-lowed by a gradual withdrawal of the medication over the next several months.
Therapy is determined on the basis of clinical criteria, includ-ing changes in pulse rate, pulse pressure, body weight, size of the goiter, and results of laboratory studies of thyroid function.
Toxic complications of antithyroid medications are relatively uncommon; nevertheless, the importance of periodic follow-up is emphasized because medication sensitization, fever, rash, urti-caria, or even agranulocytosis and thrombocytopenia (decrease in granulocytes and platelets) may develop. With any sign of infec-tion, especially pharyngitis and fever or the occurrence of mouth ulcers, the patient is advised to stop the medication, notify the physician immediately, and undergo hematologic studies. Rash, arthralgias, and fever occur in 5% of patients. Agranulocytosis, the most serious toxic side effect, occurs in 1 of every 200 pa-tients. Its incidence is higher in patients older than 40 years. It generally occurs within the first 3 months of therapy but may occur up to 1 year after it is started.
Patients taking antithyroid medications are instructed not to use decongestants for nasal stuffiness because they are poorly tol-erated. Antithyroid medications are contraindicated in late preg-nancy because they may produce goiter and cretinism in the fetus.
Thyroid hormone is occasionally administered with antithyroid medications to put the thyroid gland at rest. In this approach, hypothyroidism from excess antithyroid medication is avoided, as is stimulation of the thyroid gland by TSH. Thyroid hormone is available as thyroglobulin (Proloid) and levothyroxine sodium (Synthroid). These slow-acting preparations take about 10 days to achieve their full effect. Liothyronine sodium (Cytomel) has a more rapid onset, and its action is of short duration.
If antithyroid agents are used in elderly patients, the patient must be monitored closely because elderly patients are more likely to de-velop granulocytopenia. The dosage of other medications to treat other chronic illnesses in elderly patients may need to be modified because of the altered rate of metabolism in hyperthyroidism.
Iodine or iodide compounds, once the onlytherapy available for patients with hyperthyroidism, are no longer used as the sole method of treatment. Such compounds decrease the release of thyroid hormones from the thyroid gland and reduce the vascularity and size of the thyroid. Compounds such as potas-sium iodide (KI), Lugol’s solution, and saturated solution of potas-sium iodide (SSKI) may be used in combination with antithyroid agents or beta-adrenergic blockers to prepare the patient with hyper-thyroidism for surgery. These agents reduce the activity of the thy-roid hormone and the vascularity of the thyroid gland, making the surgical procedure safer. Solutions of iodine and iodide compounds are more palatable in milk or fruit juice and are administered through a straw to prevent staining of the teeth. These compoundsreduce the metabolic rate more rapidly than antithyroid medica-tions, but their action does not last as long.
Beta-adrenergic blocking agents are important in controlling the sympathetic nervous system effects of hyperthyroidism. For example, propranolol (Inderal) is used to control nervousness, tachycardia, tremor, anxiety, and heat intolerance. The patient continues taking propranolol until the FT4 is within the normal range and the TSH level approaches normal.
Use of beta-adrenergic blocking agents (eg, propranolol [Inderal]) may be indicated to decrease the cardiovascular and neurologic signs and symptoms of thyrotoxicosis. These agents must be used with extreme caution in elderly patients to minimize adverse effects on cardiac function that may produce heart failure.
Surgery to remove thyroid tissue was once the primary method of treating hyperthyroidism; today, surgery is reserved for spe-cial circumstances—for example, in pregnant women allergic to antithyroid medications, patients with large goiters, or patients unable to take antithyroid agents. Surgery for treatment of hyper-thyroidism is performed soon after the thyroid function has re-turned to normal (4 to 6 weeks).
The surgical removal of about five sixths of the thyroid tissue (subtotal thyroidectomy) practically ensures a prolonged remis-sion in most patients with exophthalmic goiter. Its use today is reserved for large goiters, presence of obstructive symptoms, preg-nant women, or when there is a need for rapid normalization of thyroid function (Argueta & Whitaker, 2000; Fatourechi, 2000). Before surgery, propylthiouracil is administered until signs of hyperthyroidism have disappeared. A beta-adrenergic blocking agent (propranolol) may be used to reduce the heart rate and other signs and symptoms of hyperthyroidism; however, this does not create a euthyroid state. Iodine (Lugol’s solution or potassium io-dide) may be prescribed in an effort to reduce blood loss; however, the effectiveness of this is unknown. Patients receiving iodine medication must be monitored for evidence of iodine toxicity (iodism), which requires immediate withdrawal of the medication. Symptoms of iodism include swelling of the buccal mucosa, ex-cessive salivation, coryza, and skin eruptions.
No treatment for thyrotoxicosis is without side effects, and all three treatments (radioactive iodine therapy, antithyroid med-ications, and surgery) share the same complications: relapse or recurrent hyperthyroidism and permanent hypothyroidism. The rate of relapse increases in patients who had very severe disease, a long history of dysfunction, ocular and cardiac symptoms, large goiter, and relapse after previous treatment. The relapse rate after radioactive iodine therapy depends on the dose used in treatment. Patients receiving a lower dose of radioactive iodine are more likely to require subsequent treatment than those being treated with a higher dose. Hypothyroidism occurs in almost 80% of pa-tients at 1 year and in 90% to 100% by 5 years for both the mul-tiple low-dose and single high-dose methods.
Although rates of relapse and the occurrence of hypothy-roidism vary, relapse with antithyroid medications is about 45% by 1 year after completion of therapy and almost 75% by 5 years later (Larson et al., 2000). Discontinuation of antithyroid med-ications before therapy is complete usually results in relapse within 6 months in most patients. The incidence of relapse with subtotal thyroidectomy is 19% at 18 months; an incidence of hypothy-roidism of 25% has been reported at 18 months after surgery. The risk for these complications illustrates the importance of long-term follow-up of patients treated for hyperthyroidism.
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