|Hyperthyroidism in the elderly is a great masquerader, and even severe, life-threatening hyperthyroidism can easily be missed in patients older than 60 years. A high index of suspicion is required. Graves disease and toxic multinodular goiter account for most cases in the elderly,[19, 26, 27] with the relative frequency of toxic nodular goiter being greater.[11, 28—30] Transient hyperthyroidism of subacute thyroiditis is less common and is rarely clinically significant because it is self-limited and resolves in a few weeks. Iodine-induced hyperthyroidism (Jod-Basedow disease) may be caused by increased iodine uptake from sources such as mucolytics or contrast media. Solitary toxic adenomas are rare in elder patients. Again, like hypothyroidism, the symptoms of hyperthyroidism are often atypical instead of classic and may mimic other common diseases in this age group. They may be absent, subtle, or may be obscured by coexisting diseases. Cardiac complications are the most common manifestations of hyperthyroidism in elderly. They are usually manifested as atrial arrhythmias (commonly atrial fibrillation with slow ventricular rates, as compared with high rates in young patients); congestive heart failure (usually high output heart failure) and angina pectoris. The underlying thyrotoxicosis may not be recognized, since older patients usually do not show the classic signs/symptoms of thyrotoxicosis. Symptoms may be masked by treatment for coexisting diseases; for example, in a patient taking propranolol for hypertension or angina, hyperthyroid signs of tachycardia and tremulousness may be effectively masked. The classic tremors seen frequently in younger patients are rarely seen in the elderly and if present at all are often coarse, not fine, as noted earlier in life. Rather than increased appetite, weight loss with anorexia may be present. Diarrhea is common in young hyperthyroid patients; elderly patients may note a correction of preexisting constipation but will rarely complain of loose stools. Elderly patients can present with only one symptom of hyperthyroidism, sometimes referred to as monosymptomatic hyperthyroidism. Thyroid myopathy is an example; muscle weakness is the predominant symptom and sign, but careful history and physical examination can frequently uncover other findings of thyroid disease. Neuromuscular symptoms such as decreased patient activity with fatigue, weakness, lethargy, agitation, confusion, and dementia are common.[35—38] In Graves disease, fewer of the typical clinical findings are present with each passing decade of life. Elderly patients may not have goiter, exophthalmos, or other ophthalmopathy. The symptoms may not present together, may occur alone, or may be completely absent. Only a minority of patients present with the classic features of thyrotoxicosis-tremor, tachycardia, palpitations, nervousness, exophthalmos, heat intolerance, and weight loss despite increased appetite. Untreated hyperthyroidism can also cause osteoporosis. Elderly patients may present with an apathetic form of hyperthyroidism with placid apathetic facies, depression, lethargy, muscular weakness and wasting, excessive weight loss, cardiac arrhythmias, absent or small goiter, and an absence of ocular manifestations.[40, 41] Agitation and confusion can also be presenting symptoms. Any clinical change in a previously stable elderly patient in the setting of vague or nonlocalizing symptoms should warrant thyroid evaluation.
Changes in thyroid hormone replacement therapy may result in toxic levels of thyroid hormone in the elderly as the metabolism of thyroid hormones gets slower and the half-life increases. It may take 6 to 8 weeks after dose increase to reach a steady state in those patients who are in their seventh or eighth decades of life. Failure to wait an appropriate amount of time before a dose increase may result in hyperthyroidism. One important point to remember is that even with the same dose, different brands of the hormone may cause problems due to variation in hormone potency and bioavailability from various batches of hormone. The difference may be small, but in older patients with a slower metabolism, this could have significant effects. Any patient who is not taking a consistent brand of hormone should be considered at risk.
The isolated finding of excessive amounts of circulating serum T3 is known as T3 toxicosis, an entity almost exclusively noted in the elderly, and may be the cause in up to 10% of elderly hyperthyroid patients. This condition is usually caused by a nodule producing excessive T3, which in turn may cause suppressed serum TSH and T4 levels due to the suppression of the rest of the thyroid gland.[33,43] Just like the other thyroid diseases in the elderly, it can present with atypical symptoms and along with low T4 levels, erroneously may be diagnosed as hypothyroidism.
Elevated levels of total or free thyroxine and low levels of TSH confirm the diagnosis of primary hyperthyroidism, though in a minority of patients even with low TSH level, thyroxine level may be normal. In these cases, the serum T3 should be measured to rule out T3 toxicosis. It is important to remember that TSH level may be low in some normal elderly individuals as well as patients receiving glucocorticoid therapy and patients with nonthyroidal illness (see Table 4 ). Thyroid autoantibodies suggest Graves disease. In elderly patients, physical examination of the thyroid gland is usually not helpful. Goiter is absent in more than half of these patients. If there is a palpable gland present, then a diffusely enlarged gland would be consistent with Graves disease, and a large or multiple large nodules would suggest hyperfunctioning multinodular thyroid disease. A nuclear medicine thyroid scan with iodine is not useful in hyperthyroid patients with diffusely enlarged glands. Patients with multiple or single nodules as well as a normal size gland can benefit from these scans. One caveat to remember is that a normal iodine uptake of the gland does not eliminate hyperthyroidism. In transient hyperthyroidism caused by thyroiditis, the uptake will be low or absent ( Table 5 ).
Hyperthyroidism could be a life-threatening disease in the elderly and deserves prompt attention. There are three treatment strategies for hyperthyroidism: medication to suppress the gland, surgery to remove the hyperfunctioning tissue, and radioactive iodine (RAI) to destroy the gland.
RAI has been the preferred treatment in the elderly for many reasons. There might be higher age-related risks of surgery. Many elderly are taking multiple drugs, and addition of antithyroid medications would be cumbersome. An appropriate dose of RAI is calculated from the previous thyroid uptake scan. Administration of the agent results in concentration of the RAI in the gland, and local destruction occurs. There are pitfalls to RAI therapy. Hyperthyroidism is gradually reversed over weeks to months, and cardiac problems must be managed aggressively until the thyrotoxic state is reversed. An increase in FTI measurement in the weeks after RAI administration may develop in some patients due to destruction of thyroid cells with transient release of active thyroid hormone in circulation, which may, in rare cases, result in life-threatening thyroid storm. Antithyroid medications may be added for a few weeks before RAI treatment to control this excess hormone surge. If the hyperthyroid state persists for several months after the RAI treatment, a second course may be used. The final measure of success may be development of hypothyroidism, but timing is unpredictable. Some patients progress from hyperthyroidism to euthyroidism to hypothyroidism; others may become euthyroid for a period of time and then have development of hypothyroidism. A few patients may become euthyroid permanently. TSH is the test of choice to determine the development of hypothyroidism in patients who have undergone RAI treatment. Thyroid hormone should be started when the TSH starts increasing and FTI is still normal.
Drug therapy is very effective, but potential for side effects plus the high recurrence rate render them not as popular as a treatment of choice. The antithyroid drugs (propylthiouracil or methimazole) have a special role in those elderly patients whose unstable comorbid disease warrants a rapid suppression of hyperthyroid state, since these medicines act quickly. These medications should be used for a short period in the elderly; when the patient is euthyroid and stable, a decision should be made about the definitive treatment. Typical initial dose for propylthiouracil is 100 mg four times daily and for methimazole, 10 mg four times daily. Agranulocytosis is the major adverse reaction but occurs in less than 0.5% of those treated. It tends to occur early in the course of treatment and is more common with larger doses. It is usually abrupt in onset and occasionally fatal but reversible on discontinuation of therapy. Baseline leukocyte count with repeat testing with the onset of sore throat, fever, or other signs of infection is recommended. Rash, arthralgia, and myalgia are other potential side effects.
Surgery is a less attractive option in elderly patients with hyperthyroidism due to the presence of multiple chronic medical conditions including cardiac problems in this population. In some elderly patients, RAI may not work fully in the presence of multinodular toxic goiter or a large single hyperfunctioning nodule. In these patients, surgical intervention may be necessary. Surgery may also be necessary in those patients who have dysphagia or tracheal compression or if there is suspicion of malignant disease.
Beta-blockers can be used initially to control tachycardia and tremors but cannot alter the natural history of the disease. Calcium channel blockers (eg, diltiazem) can be chosen if beta-blockers are contraindicated. Anticoagulation may be indicated if patients present with atrial fibrillation, remembering that lower doses of warfarin are needed in hyperthyroid patients.
Psychiatric features, including overt psychosis, disappear when patients become euthyroid, so psychiatric symptoms should be treated with psychologic support. If psychosis or other psychiatric symptoms persist after the patient is euthyroid, psychotropic drugs could be used for a short period of time. Free T4 levels should be monitored frequently, even after they are within the normal range, as the TSH remains suppressed for a while.
It can present with fever, delirium, tachycardia, hypotension, vomiting, diarrhea and jaundice, and abnormal liver function tests. It can be precipitated by surgery, anesthesia induction, and systemic infections. Hyperthyroid storm requires intensive care with close supervision. It is treated with antithyroid drugs, iodine (to inhibit thyroid hormone release), glucocorticoids, beta-blockers, and occasionally iopanoic acid (to inhibit T4 to T3 conversion).
|The causes of primary hypothyroidism in the elderly include thyroid autoimmune disease, neck irradiation, and previous surgical or medical treatment of hyperthyroidism as well as drugs such as lithium or amiodarone.[4, 10, 11] The classic signs and symptoms of hypothyroidism in younger patients, for example, cold intolerance, weight gain, dry skin, constipation, and mental and physical slowing, can easily be mistaken for normal aging.[7, 12] In many elderly patients, the coexistence of multiple chronic diseases as well as the side effects of medications can further mimic or mask the symptoms and signs of hypothyroidism. For example, in an elderly man taking metoprolol, amlodipine, and digoxin for hypertension, congestive heart failure and atrial fibrillation, complaints of weakness, fatigue, constipation, and weight gain can readily be attributed to medical illness or medication, whereas hypothyroidism could also be the cause of these symptoms. Musculoskeletal and mobility disorders are common in the elderly, with hypothyroidism caused by generalized weakness and delayed contraction and relaxation phases of the deep tendon reflexes. Carpal tunnel syndrome may be a manifestation of hypothyroidism. Serum cholesterol and triglyceride level elevation are also common in patients with hypothyroidism. Depression and dementia in the elderly may be associated with thyroid disease. Both are reversible with proper treatment. Hypothyroidism may cause decreased memory and slowed speech and thinking. Both hypo- and hyperthyroidism can cause symptoms consistent with depression.[14, 15] Cerebellar dysfunction, neuropathy, and macrocytic anemia with or without pernicious anemia may also be manifestations of thyroid abnormalities in the elderly. Unexplained hyponatremia, elevated creatinine phosphokinase, and lactate dehydrogenase may be caused by a deficiency of thyroid hormones. In patients who are receiving thyroid replacement therapy, other concomitant medications can alter the thyroid hormone level as the result of their effects on the iodine absorption or binding. For example, intestinal sequestrants used as lipid-lowering agents can interfere with the intestinal absorption of thyroid hormone.
Low FTI with high thyroid-stimulating hormone (TSH) establishes the diagnosis of primary hypothyroidism ( Table 3 ). Thyroid autoantibodies may help define the cause. If the thyroid is normal on examination and there is no substernal enlargement of the gland on the chest radiograph, no further testing is needed. If the gland is asymmetric or hard, further evaluation with thyroid scanning and tissue sampling is needed. Myxedema coma is the only indication for high doses of thyroid hormones; in all other circumstances, the starting dose of T4 (levothyroxine, eg, Synthroid, Knoll Pharmaceuticals, Mt. Olive, NJ) should be extremely low. Cardiac complications such as angina, infarction, and arrhythmias may occur with an iatrogenic excess of T4. It is important to note that the hypothyroid state develops over a prolonged period, and correction should be made slowly over a period of months. The starting oral dose of T4 in the elderly is 25 µg, but if there is any uncertainty regarding the cardiac status, start with 12.5 µg daily.[12,18] The dose should be increased by small increments of 12.5 to 25 µg, every 2 to 4 weeks. Pulse rate should be monitored for tachycardia.[19, 20] Physiologic dose in the elderly is approximately 75 µg daily.[7,17] If thyroid replacement therapy causes cardiac instability, that is, heart failure, angina, or arrhythmia, then the dose should be held for several days to weeks. Cardiac evaluation before adjusting the dose any further should be undertaken. As the half-life of T4 in elderly patients is sufficiently long, interruption in therapy for several days does not cause any clinical problem. TSH can be used for monitoring. FTI may need to be checked, since there may be a delay in downregulation of TSH secretion. It is not unusual to find a patient who is euthyroid by FTI measurement, but the TSH is still slightly elevated. A slight elevation of TSH in a euthyroid elderly patient early in the course of thyroid replacement may not indicate the need for further increase in thyroid hormone. The TSH may fall to normal over a period of months without further increase in thyroid hormone replacement. If after 1 year the TSH remains elevated, a small increase in T4 (12.5 µg) may be warranted. Most patients require lifelong therapy. Once a steady state of FTI and TSH levels has been achieved, patients should be monitored every 6 to 12 months for clinical response to the treatment, adherence to medication, and observation of drug interactions. Education of the patient and family is very important, since in many elderly individuals coexisting memory impairment may cause nonadherence to the therapy, and inadequately treated hypothyroidism can lead to further mental impairment.
Secondary hypothyroidism is rare. Patients with pituitary or hypothalamic problems may have a concomitant deficiency of glucocorticoid hormones. Thyroid hormone accelerates the metabolism of cortisol; if these patients are treated with thyroid hormone without correcting the cortisol deficiency, fatal adrenal crisis may result. If urgent therapy is necessary and it is uncertain whether the hypothyroidism is primary or secondary, the patient should be treated with stress doses of cortisone and thyroid hormone until the pituitary state is known.
This rare complication of hypothyroidism usually affects patients older than 75 years. Severe mental deterioration, confusion, and disorientation as well as lethargy and psychosis characterize it. Other features are dry, scaly, and yellowish skin, sparse hair, thin eyebrows, hoarse voice, bradycardia, cardiomegaly, pericardial effusion, hypothermia, hyponatremia, and pseudomyotonic reflexes. Usually a major physiologic stress, for example, sepsis or intoxication with alcohol or narcotic/sedative medication, can precipitate the event, and a state of profound lethargy or coma ensues. Medications such as lithium and amiodarone have been implicated in the development of myxedema coma. Exposure to cold temperature may also precipitate the event. Cold exposure risk is not limited to extreme temperatures; poorly heated homes can also bring on the complication. Myxedema coma should be treated in an intensive care unit; with supportive care, such as ventilatory support, as well as administration of intravenous 250 to 500 µg levothyroxine to replenish body stores. Treatment for possible hypocortisolemia must also be started until the pituitary-adrenal status is known.
Preclinical or Subclinical Hypothyroidism
An elevated TSH level occurs in almost 20% of patients older than 65 years; most of them are clinically euthyroid, with no symptoms and with normal FTI. Whether to treat or to follow this group of patients is unclear. Most physicians favor treatment with low doses of hormone[23,24] due to potential risks of progression to overt hypothyroidism or development of thyroid goiter. If the patient is clinically stable, it is probably reasonable to treat them with 50 to 75 µg of levothyroxine.
Euthyroid Sick Syndrome
The hypothalamic-pituitary-thyroid axis is affected by a nonthyroid illness. The syndrome is acute, reversible, and occurs commonly after surgery, during fasting, in many acute febrile illnesses, and after acute myocardial infarction. Malnutrition, renal and cardiac failure, hepatic diseases, uncontrolled diabetes, cerebrovascular diseases, and malignancy can also produce abnormalities in the thyroid function tests. Almost any condition that can make a person ill can cause euthyroid sick syndrome (ESS, also called low T3 syndrome), and the elderly are most susceptible because of multiple comorbid conditions. Sick patients show a confusing array of thyroid abnormalities. Any abnormality in hormone level is possible, though usually T3, T4, and FTI are low and TSH could be low or normal, mimicking central hypothyroidism, but these patients usually have high cortisol levels. Reverse T3 (rT3) is usually elevated and can be a useful test. Acute and chronic illness, starvation, and drugs inhibit the activity of 5' deiodinase. This enzyme generates T3 by removing iodine from the outer ring of T4. There is a second enzyme that removes iodine from the inner ring of T4, the activity of which is not affected by the process listed above. Removing the iodine from the inner ring of T4 yields physiologically inactive reverse T3 (rT3); its function is unknown but its level increases with decreased outer ring deiodination. As patients recover from their illness, TSH may normalize or become elevated. Ideally, the thyroid function tests should not be performed during any nonthyroid illness, but this may not be practically applicable, so any abnormal results should be interpreted with caution and with a realization that ESS is a more likely explanation for the finding than true thyroid disease. Thyroxine replacement has not been beneficial and should not be used in patients with ESS. If there is any confusion about the thyroid status, it is always best to check rT3 levels, as it is always elevated in ESS.