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General Principles in Older Adults
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Hyperthyroidism is the result of an excessive amount of circulating thyroid hormone either from endogenous production or iatrogenic sources. Clinically, this disorder is accompanied by a broad spectrum of signs and symptoms that vary among individuals and can differ markedly between young and old persons. A greater percentage of affected individuals is older than age 60 years. Several studies of prevalence indicate the presence of hyperthyroidism in 1% to 3% of community-residing older persons. Hyperthyroidism is far more common in women than in men, with estimates ranging from 4:1 to 10:1.
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Graves disease remains the most common cause of hyperthyroidism in young persons, and may still be present in older patients. With increasing age, however, more cases of hyperthyroidism result from multinodular toxic goiter. Although multinodular goiters are commonly found in older persons and are not usually associated with clinical disease, they may evolve into toxic multinodular thyroid goiters. A toxic adenoma may cause hyperthyroidism and is usually identified on thyroid scan as a solitary hyperfunctioning nodule with suppression of activity in the remaining portion of the thyroid gland.
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Rarely, hyperthyroidism may result from ingestion of iodide or iodine-containing substances. Iodine may be introduced from seafood, although this problem is more common after exposure to iodinated radiocontrast agents and to amiodarone. Up to 40% of patients taking amiodarone will have serum T4 levels above the normal range as a result of the drug’s effect on T4 metabolism; far fewer (5%) will develop clinically apparent thyrotoxicosis. The hyperthyroidism can be of rapid onset and severe in magnitude.
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Hyperthyroidism must always be considered in the older person who is already receiving thyroid hormone therapy. This is particularly important if the dose is >0.15 mg of L-thyroxine daily, although even smaller doses may be excessive, especially in small individuals of advanced age. Persons taking the same dose of thyroid hormone for many years may become hyperthyroid simply because of an age-associated decline in the body’s ability to degrade T4.
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Although extremely rare, a TSH-producing pituitary tumor may be the cause of hyperthyroidism. Nonsuppressed levels of serum TSH in the presence of increased amounts of circulating thyroid hormone are seen with these tumors. Hyperthyroidism may also rarely result with overproduction of thyroid hormone from a widespread metastatic follicular carcinoma.
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Transient hyperthyroidism may occur in patients with silent or subacute thyroiditis as a result of increased release of thyroid hormone into the circulation during the inflammatory phase of the illness. Radiation injury, which may be caused by radioactive iodine therapy for hyperthyroidism, may also result in an outpouring of thyroid hormone.
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Hyperthyroidism is usually accompanied by elevated levels of both T4 and T3. However, a subgroup of older hyperthyroid individuals have isolated elevations of T3 alone. T4 is either within the normal range or may, in fact, be suppressed. This circumstance is referred to as T3 toxicosis. Although it can occur with any type of hyperthyroidism, it is most commonly seen in older patients with toxic multinodular goiter or solitary toxic adenomas. The diagnosis is made on clinical grounds and measurements demonstrating an elevated level of serum T3 and a suppressed level of serum TSH. T4 toxicosis, or an isolated increase in serum T4 without an elevation in serum T3, most commonly occurs in a sick older person with hyperthyroidism. Disease or malnutrition interferes in the normal removal of iodine from the 5′ position of T4 and thus a decreased ability to convert T4 to T3.
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Clinical findings associated with hyperthyroidism in the older adult vary greatly. In general, the clinical presentation of hyperthyroidism at this time of life differs from the more classic findings noted earlier in life (Table 41–1). The presenting feature may be a decline in functional capacity. There may be increased fatigue, muscle weakness, cognitive changes, loss of appetite, weight loss, cardiac arrhythmias, and congestive heart failure. Eye findings associated with the hyperthyroidism are less commonly noted in older adults. Rather than frequent bowel movements, more commonly there is a resolution of preexisting constipation. Anemia and hyponatremia are often noted and thought to be caused by other coexisting illnesses. Although this relative lack of the classic findings of hyperthyroidism does not occur in every older person with hyperthyroidism, a subgroup develops an apathetic hyperthyroid state. In this circumstance, the patient lacks the hyperactivity, irritability, and restlessness common to young patients who are hyperthyroid and presents instead with severe weakness, lethargy, listlessness, depression, and the appearance of a chronic wasting illness. Often the person is incorrectly diagnosed as having a malignancy or severe depression.
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Symptoms less common in older patients include nervousness, increased diaphoresis, increased appetite, and increased frequency of bowel movements. More common symptoms include marked weight loss, present in >80% of older patients, poor appetite, worsening angina, agitation, confusion, and edema.
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Similarly, physical findings differ in older patients. Hyperreflexia, palpable goiter, and exophthalmos are usually absent, although lid lag and lid retraction may be present. The pulse rate tends to be slower. Cardiac manifestations are particularly important in the older person who may have coexisting heart disease. An increased heart rate with a related increase in myocardial oxygen demand, stroke volume, cardiac output, and shortened left ventricular ejection time underlie the clinical consequences of palpitations. There is also an increased risk of atrial fibrillation (often with slow ventricular response), exacerbation of angina in patients with preexisting coronary artery disease, and precipitation of congestive heart failure that responds less readily to conventional therapy.
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Gastrointestinal problems may occasionally include abdominal pain, nausea, and vomiting. Diarrhea and increased frequency of bowel movements resulting from the effect of the thyroid hormone on intestinal motility can occur, but these symptoms are often absent and constipation is still common. There may be an alteration in liver enzymes, including elevation of alkaline phosphatase and γ-glutamyltranspeptidase levels, which become normal after a return to the euthyroid state. Weakness, especially of proximal muscles, is a major feature of hyperthyroidism in older persons and is often accompanied by muscle wasting and functional decline. Disorders of gait, postural instability, and falling may be noted. Tremor is noted in >70% of older persons with hyperthyroidism. The tremor is usually more coarse than in other common tremors. A rapid relaxation phase of the deep tendon reflex is difficult to identify in the older thyrotoxic individual. Central nervous system (CNS) manifestations may be prominent and include confusion, depression, changes in short-term memory, agitation and anxiety, and a decreased attention span. Other findings associated with hyperthyroidism include worsening of glucose tolerance, mild increases in serum calcium, and osteoporosis resulting from increased bone turnover.
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The altered and often atypical presentation of hyperthyroidism in the older patient warrants a high degree of suspicion among clinicians and the initiation of appropriate laboratory studies. Serum free T4 and a measurement of serum TSH are the preferred tests for diagnosing thyroid dysfunction. The findings of a normal or low serum free T4 with a suppressed serum TSH raises the possibility of T3 toxicosis and warrants a measurement of serum T3 by radioimmunoassay. Although the finding of anti-TSH receptor antibodies confirms the diagnosis of Graves disease, it is rarely necessary to obtain this test.
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Thyroid scanning with technetium and measurement of 24-hour 131I uptake can be useful in distinguishing Graves disease from toxic multinodular goiter. Scanning may also demonstrate the presence of a small, diffusely active goiter that could not be detected on physical examination. Very low 131I uptake in a patient with elevated circulating thyroid hormone levels suggests exogenous thyroid hormone ingestion, the hyperthyroid phase of painless or subacute thyroiditis, or iodine-induced hyperthyroidism.
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Differential Diagnosis
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Patients with hyperthyroidism in later life commonly have coexisting illness, and it is important not to attribute all presenting signs and symptoms to the hyperthyroid state itself. The most common differential diagnoses to consider include anxiety, malignancy, depression, diabetes mellitus, menopause, and pheochromocytoma.
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Therapy should be directed at the specific cause of the hyperthyroid state. Therefore, the underlying cause must be determined to exclude the possibility of one of the transient forms of illness, such as excessive hormone ingestion, iodine exposure, or subacute thyroiditis. The majority of older patients with either Graves disease or multinodular toxic goiter can be treated with antithyroid medications, radioactive iodine, or surgery. The preferred treatment, however, is radioactive iodine.
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A useful initial step in treating suspected hyperthyroidism is to administer a β-adrenergic blocking agent such as long-acting propranolol, metoprolol, nadolol, or atenolol. These agents quickly control associated palpitations, angina, tachycardia, and agitation. Caution is advised, however, in persons with congestive heart failure, chronic obstructive pulmonary disease, or diabetes mellitus being treated with insulin.
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Once a diagnosis of Graves disease or toxic nodular goiter is confirmed, treatment should be initiated with one of the antithyroid drugs: propylthiouracil or methimazole. These agents impair biosynthesis of thyroid hormone, thus depleting intrathyroidal hormone stores and ultimately leading to decreased hormone secretion. A decline in serum T4 concentration is usually seen within 2–4 weeks after initiation of antithyroid drug therapy, and the dose should be tapered once thyroid hormone levels reach the normal range to avoid hypothyroidism. In 1% to 5% of patients, the antithyroid medications may result in fever, rash, and arthralgias. A drug-induced agranulocytosis may be more common in older patients and will most likely occur within the first 3 months of treatment, especially in those who receive >30 mg/day of methimazole. Periodic white blood cell count monitoring should be considered, with discontinuation of the antithyroid medication if there is evidence of neutropenia.
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Long-term antithyroid medication use can be effective in patients older than age 60 years with Graves disease, who appear to respond fairly quickly and have a greater likelihood of a long-lasting remission. Because these medications rarely will provide a long-lasting effect for those with a toxic multinodular goiter, more definitive therapy is needed once the patient returns to an euthyroid state on medication. The recommended treatment in most older persons with hyperthyroidism is thyroid gland ablation with 131I. Once the patient achieves a euthyroid status on antithyroid medication, these agents should be stopped for 3–5 days, after which 131I is given orally. Therapy with β blockers can be maintained and antithyroid agents restarted 5 days after radiotherapy and should be continued for 1–3 months until the major effect of radioiodine is achieved. Although some physicians attempt to calculate a specific dose that will render the patient euthyroid without subsequently developing hypothyroidism, many patients will still develop permanent hypothyroidism. For this reason, most clinicians advocate treating the older person with hyperthyroidism with a relatively large dose of 131I to ensure ablation of thyroid tissue and thus avoid the possibility of hyperthyroidism recurrence.
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After treatment, the patient is closely monitored in order to start replacement doses of thyroid hormone, because hypothyroidism may develop in as few as 4 weeks after treatment. Regardless of dosing regimen used, 40% to 50% of patients will be hypothyroid within 12 months of 131I administration, with 2% to 5% developing hypothyroidism each year thereafter.
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Prior treatment with antithyroid medication prevents the possibility of radiation-induced thyroiditis after 131I therapy. However, in some circumstances, when clinical and laboratory features suggest a mild case of hyperthyroidism and no cardiac problems are noted, it may be appropriate to treat the hyperthyroid patient with 131I without antithyroid medication pretreatment. When this option is chosen, the patients should be started on a β-blocker and continue with it until thyroid hormone levels return to normal.
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Surgery is not recommended as a primary treatment for hyperthyroidism in older patients. Coexisting illness, particularly cardiac, increases operative risk. In addition, postoperative complications of hypoparathyroidism and recurrent laryngeal nerve damage are significant risks. Surgery may be indicated in the rare patient with tracheal compression secondary to a large goiter.
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Atrial fibrillation occurs in 10% to 15% of hyperthyroid patients. Treatment of the underlying disease is essential; cardioversion and anticoagulation are considered on an individual basis. The longer the hyperthyroid period, the less likely is the return to normal sinus rhythm; most benefit is found in those who become euthyroid within 3 weeks. Cardioversion is usually reserved for those patients who still remain in atrial fibrillation after 16 weeks of euthyroidism. Many older individuals with hyperthyroidism who develop atrial fibrillation are at greater risk of thromboembolic events, especially those with a history of thromboembolism, hypertension, or congestive heart failure and those with evidence of left atrial enlargement or left ventricular dysfunction. In the absence of contraindications, anticoagulant therapy should be given with warfarin in a dose that will increase the international normalization ratio to 2.0–3.0. Warfarin should be continued until the patient is euthyroid and normal sinus rhythm has been restored.
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Allahabadia
A, Daykin
J, Holder
RL, Sheppard
MC, Gough
SC, Franklyn
JA Age and gender predict the outcome of treatment for Graves’ hyperthyroidism.
J Clin Endocrinol Metab. 2000;85(3):1038-–1042.
[PubMed: 10720036]
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Trivalle
C, Doucet
J, Chassagne
P
et al Differences in the signs and symptoms of hyperthyroidism in older and younger patients.
J Am Geriatr Soc. 1996;44(1):50-–53.
[PubMed: 8537590]