Hypothyroidism and Hyperthyroidism in the Elderly

Author: Jonathan Glauser, MD, FACEP, Attending Staff, Cleveland Clinic Foundation; Faculty, Emergency Medicine Residency Training Program, Metro Health Medical Center, Cleveland, OH

Peer Reviewer: Gary R. Strange, MD, Professor and Head, Department of Emergency Medicine, University of Illinois at Chicago.

Thyroid disease may have a variety of manifestations. In the younger population, many symptoms are characteristic, while thyroid disease in the elderly may present with much more nonspecific findings. Although thyroid disease is quite common, thyroid-related emergencies are rare and require a high index of suspicion to address their high rate of mortality.

The total prevalence of the disorders of hyperthyroidism and hypothyroidism in adolescents and adults is estimated to be 1-4% in the United States. The annual incidence for hypothyroidism is 0.08-0.2%, with higher incidence cited in the elderly female population. Subclinical hypothyroidism as defined by elevated thyroid stimulating hormone (TSH) exists in 6-8% of adult women and 3% of adult men, with slightly greater prevalence in whites (vs blacks), in women, and in people older than 75 years of age.1,2 In one report, the prevalence of hypothyroidism was 10.3% in the elderly.3 In another, hypothyroidism was found to affect approximately 8% of women and 2% of men older than 50 years.4 Progression to clinical hypothyroidism occurs in fewer than 2% in those without thyroid antibodies.5,6 The elderly may be prone to thyroid dysfunction for several reasons. The incidence of autoimmune thyroiditis and nodular goiter rises with age. These conditions predispose to hypothyroidism and hyperthyroidism, respectively.— The Editor

Lab Tests for the Diagnosis of Thyroid Disease

In general, serum TSH, also known as thyrotropin and free thyroxine (free T4) will suffice in the emergency department (ED) to make the diagnosis of thyroid emergencies. However, an overview of individual tests should give the emergency physician an idea of the role of specific testing in the diagnosis of thyroid disorders.

There will be specific instances in which any of the following tests may be utilized in the acute setting:

Free T4 (reference range 0.7-1.8 ng/dL) is actually a prohormone, converted by de-iodination in peripheral tissues—largely liver and kidney—to triiodothyronine (T3), the more active form. The thyroid gland is the sole source of T4, normally the predominant circulating hormone. Free T4 measures the nonprotein-bound circulating T4;

Total T4 (normal range 50-120 ng/mL, or 5-12 mcg/dL) measures all T4. Multiplying by T3 resin uptake is designed to correct for variation in plasma proteins. Measurement of total T4 is not particularly helpful, as it is dependent upon total albumin and thyroid-binding globulin, which may be affected by non-thyroidal illness such as liver disease. Only 0.03% of T4 circulates in the unbound state.7 There is no clinical indication for performing total thyroid hormone measurements8; and

TSH (normal 0.4-5.5 mIU/L) should be measured using a third generation assay sensitive at low levels for detecting hyperthyroidism. Serum TSH will be decreased to < 0.1 mIU/L in all hyperthyroid patients except in rare instances of hyperthyroidism due to inappropriate secretion of TSH. First generation assays detect serum TSH to about 0.1 mIU/L, third generation to 0.01-0.03 mIU/L.9 The findings of a low serum T4 and low TSH mandate a search for pituitary disease, although the patient’s thyroid function tests may be related to non-thyroid illness (the euthyroid sick syndrome).

T3 is the more biologically active form of thyroid hormone, formed when T4 is converted by de-iodinases in the kidneys, liver, pituitary, and hypothalamus. It circulates bound to several binding proteins, including thyroid-binding globulin, trans-thyretin (prealbumin), and albumin. Some feel that free T4 alone is adequate to document the hyperthyroid state, while others feel that a free T3 is necessary to gauge the true severity of biochemical hyperthyroidism.10 An increased free T3 level occurs in approximately 5% of clinically hyperthyroid patients with a normal free T4 level (T3 thyrotoxicosis).11

Functional examinations measure the uptake of iodine, or a surrogate marker, into the thyroid gland. These tests all use radioisotopes, and include I-123, I-131, technetium-99, and thallium-201. The iodine isotopes can be used to identify nodular thyroid disease, to determine if these nodules are hot (functioning) or cold (hypofunctioning), to determine the cause for the hyperthyroid state (Graves’ disease vs thyroiditis), and to determine a dose of radioiodine for treatment. Radioiodine uptake will be elevated in nearly all cases of thyroid storm, and can be accomplished over a two- to six-hour period. A 24-hour radioactive uptake will confirm whether thyrotoxicosis is due to true excess production of thyroid hormones; and

An erythrocyte sedimentation rate may be drawn to confirm the diagnosis of subacute (viral) thyroiditis in patients with tenderness on thyroid palpation and decreased thyroid uptake on nuclear scan. In these cases, thyrotoxicosis tends to be mild, and thyroid uptake on scan will be low.

Hypothyroidism

Overview. Despite the relative high prevalence of hypothyroidism, true emergencies, including myxedema coma, are rare. There is little objective evidence upon which to base diagnosis and triage disposition of thyroid emergencies, since no comparative studies have been done. Suggested therapies are based on the practice guidelines and recommendations of experts. Until 1996, only about 200 cases of myxedema coma were reported in the literature.12

Hypothyroidism mimics a great number of other disease entities in medicine, presenting in many possible ways including fatigue, anemia, cold intolerance, change in mental status, and a variety of other symptoms. (See Table 1.) With the availability of rapid thyroid hormone assays now available, the diagnosis of hypothyroidism can be made promptly. True emergencies, however, continue to be evident clinically, and require laboratory tests mainly to confirm the diagnosis. Hypothyroid coma, or myxedema coma, requires prompt recognition and treatment since it carries a mortality rate approaching 60%.12 Cases of hypothyroidism that require laboratory testing to make the diagnosis generally will not be emergencies and, as a rule, can be referred for initiation of outpatient treatment.

The Role of the History in Diagnosing Hypothyroidism. Patients with previous thyroid ablation or a history of elevated thyroid autoantibodies have been shown to progress to overt clinical hypothyroidism. A history of thyroid surgery or a history of medications containing lithium or iodine is suggestive.13 The most common cause of hypothyroidism is autoimmune or Hashimoto’s thyroiditis, suggested by the presence of antithyroid microsomal antibodies.14

Signs and Symptoms. The hypothyroid state may present in myriad ways, many of which are nonspecific. The patient may be less active than usual, with loss of interest in things previously enjoyed. Lethargy may be a prominent complaint, as is decreased mobility.15 Misdiagnosis as depression is common. Fatigue and dry skin may be prominent complaints. Caregivers may report that the patient has been acting confused, with memory problems.16 The usual clinical findings in the elderly population are apathy and psychomotor retardation, which may develop over a long period of time.17

Patients also may present with weakness, arthralgias, and myalgias. Coarsening of the voice may have been noted. Lethargy, dry skin, constipation, edema, and weight gain may be elicited in the history.18 A history of cold intolerance is typical.

There is a diminished ventilatory drive, possibly leading to alveolar hypoventilation, carbon dioxide (CO2) retention, and coma. An impaired ventilatory drive leads to increased sensitivity to sedative drugs. Obesity and sleep apnea may contribute to respiratory alterations.

The Physical Examination in Hypothyroidism. Vital signs suggestive of the hypothyroid state include hypotension or diastolic hypertension. Body temperature is below normal in 80%, and bradycardia may be present.19,20 Classically, patients with hypothyroidism have facial features that are puffy and coarse.

The skin may be dry and cold. An orange or yellow tint without scleral icterus indicates carotenemia. Most patients have varying degrees of brittle nails and hair. Acid glycosaminoglycans in the papillary and reticular layers may cause the skin to exhibit pallor, induration, and thickening.21 Periorbital edema and macroglossia may be present. Myxedema is a peculiar non-pitting edema of the skin, classically of the lower extremities.

Neurologic findings may include mental status changes. Delayed relaxation time of deep tendon reflexes is variably present. Physical evidence of effusions into the pleural, peritoneal, or pericardial cavities may be detectable. Delirium and psychosis may be present, characteristic of "myxedema madness."

The Heart in the Hypothyroid State. Inotropic and chronotropic alterations of hypothyroidism may be manifested by decreased stroke volume, bradycardia, and decreased cardiac output. Peripheral vasoconstriction shunts blood away from the skin and muscle to maintain core body temperature. Diminished beta-receptor responsiveness leads to unopposed alpha activity and contributes to the diastolic hypertension seen in hypothyroidism.10

The electrocardiogram (ECG) may show a variety of abnormalities. Sinus bradycardia and a prolonged PR and QT intervals may be present. Low voltage as evidence of a pericardial effusion may be present. Heart block and T-wave flattening or inversion may be present, but ST abnormalities are nonspecific. Torsades de pointes with marked QT prolongation and sudden death have been reported in association with the hypothyroid state.22,23

Echocardiography may be useful to show regional wall abnormalities and to verify infiltrative cardiomyopathy. It also will diagnose a pericardial effusion, which may occur in 30-80% of severely hypothyroid patients.24 Pericardial tamponade is rare, so a pulsus paradoxus and distended neck veins are not common findings.25 A normal echocardiogram does not rule out myocardial infarction.

Laboratory Diagnosis. TSH and free T4 levels are needed to confirm the diagnosis of hypothyroidism. The normal range for TSH is 0.4-5.5 IU/L, and levels are invariably high. Rarely, TSH may be decreased if there is a central (hypothalamic or pituitary) cause.26 In unselected populations, TSH has a sensitivity of 89-95% and a specificity of 90-96% for overt thyroid dysfunction.27 Subtle abnormalities in these tests can be found but do not warrant further work-up in the ED since they can be referred to outpatient care. The normal range for free T4 is 0.7-1.8 ng/dL or approximately 12-30 pmol/L, and will be decreased in hypothyroidism.

Possible non-thyroid laboratory abnormalities are numerous, and warrant investigation in the proper clinical setting. A macrocytic anemia due to vitamin B12 deficiency may be present. Erythropoietin levels also are low, leading to a fall in hematocrit, typically to approximately 30%.10

Hyponatremia with low serum osmolality is characteristic of hypothyroidism, and should respond to thyroid hormone replacement.28 Hyponatremia may be due to reduced free water clearance, reduced renal blood flow and glomerular filtration, and elevated plasma vasopressin levels. Hypoglycemia occurs because of increased insulin sensitivity, along with decreased gluconeogenesis and glycogenolysis.1,10,29

Cardiac enzymes such as aspartate aminotransferase (AST/SGOT) or creatine kinase (CK) may be elevated as a result of increased muscle membrane permeability and reduced metabolic clearance.28 However, in severe hypothyroidism without acute MI, the troponin I level remains normal.30

Adrenal hypofunction is important to consider following a diagnosis of severe hypothyroidism. Central hypothyroidism may be associated with adrenocorticotropic hormone deficiency, and primary hypothyroidism may be associated with primary adrenal insufficiency (Schmidt syndrome). Serum prolactin levels (normal range 1-25 mcg/L), growth hormone levels (normal range < 880 pmol/L), and luteinizing hormone (LH) levels (normal range 6-30 IU/L), and follicle-stimulating hormone (FSH) levels (normal range 6-30 IU/L) may help delineate this, but are of little value in the emergency setting.28

In the non-emergency setting, thyroid antibody tests may elucidate the etiology of the hypothyroid state. Elevation of thyroid microsomal antibodies is consistent with a diagnosis of chronic autoimmune (Hashimoto’s) thyroiditis. Thyroid antibodies may be associated with Graves’ disease, vitiligo, myasthenia gravis, Addison’s disease, pernicious anemia, and other autoimmune diseases.

Myxedema Coma. The hypothyroid crisis of myxedema coma is a life-threatening manifestation of the hypothyroid state. Myxedema coma can be defined as severe thyroid hormone deficiency contributing to a decreased level of consciousness.1 In severe decompensated hypothyroidism, respiratory depression is characteristic as a result of respiratory muscle weakness and upper airway obstruction due to an enlarged tongue and myxedematous infiltration of the upper airway. Defective thermoregulation is characteristic of myxedema coma. It most frequently is encountered in patients with a known history of hypothyroidism in the winter months, often after cold exposure. Thyroid hormone exerts its action by stimulating calorigenesis via sodium/potassium ATPase, and most of the clinical features of myxedema coma are related to the failure of this action. The diagnosis of myxedema coma is largely a clinical one. In the presence of nonpitting edema, hypothermia, hypoventilation, and stupor, abnormal TSH and free T4 values confirm the diagnosis.31 Hyponatremia, hypoglycemia, and associated infection are confirmatory.

Three findings are required to make the diagnosis of myxedema coma: 1) A precipitating illness or event; 2) defective thermo-regulation (hypothermia); and 3) altered mental status.

The typical presentation is that of elderly women in the winter. Approximately 80% of myxedema coma cases occur in females.32 There is usually a history of hypothyroidism, hypopituitarism, or use of antithyroid medications.10 True myxedema coma is rare, and to a certain extent depends on one’s definition. One report noted only 24 cases during a two-year period in Germany, of which 12 were re-classified by the authors as severe hypothyroidism without coma.33 Another study reported 200 cases in the literature between 1953 and 1986.34-36

Precipitating Events for Myxedema Coma. Potential precipitating events for myxedema coma are numerous, and include surgery, severe infection, and trauma.29 Some medications, including sedatives, narcotics, and tranquilizers, as well as missed doses of T4, may be implicated.4,37,38 (See Table 2.)

Clinical Features of Myxedema Coma. Myxedema coma may present with many features of the hypothyroid state. (See Table 3.) Recognition may be hampered by its insidious onset and rarity. The characteristic four features facilitating the diagnosis include: alteration in mental status, presence of a precipitating factor, hypothermia, and increased serum CK levels.39

The patient typically appears pale and edematous. Periorbital edema is common. The lateral eyebrows may be missing. A neck scar might be a clue to a previous thyroidectomy.

Respiratory symptoms may be related to stupor, obesity, and to the large myxedematous tongue which, along with aspiration, may cause obstruction of the upper airway. Myxedematous patients exhibit decreased respiratory drive in response to carbon dioxide.40,41 Ascites, pericardial effusions, and pleural effusions related to the hypothyroid state may impede effective ventilation. Defective cough reflex, inability to clear secretions, and sleep apnea all may contribute to respiratory acidosis.21

Cardiac sounds may be distant. Usually, bradycardia is present. Classically, high serum cholesterol levels are present, along with low voltage on the ECG.

With longstanding hypothyroidism, patients may develop various cardiac manifestations. Dyspnea on exertion, fatigue, and edema may be a result of pericardial effusion or congestive heart failure. Patients have an increased incidence of hypercholesterolemia and hypertriglyceridemia. The decreased metabolic demands on the heart may be protective from myocardial infarction and angina.42

Gastrointestinal findings include signs of decreased motility. The abdomen is distended, and paralytic ileus and fecal impaction may be present. Myxedema megacolon is an unusual and late finding, appearing as pseudomembranous colitis and intestinal ischemia.43

All patients with myxedema coma display deterioration of their mental status. Central nervous system findings may include disturbances in consciousness ranging from delirium to stupor and coma. Some of the depressed level of consciousness as well as seizures have been attributed to hyponatremia. Hallucinations ("myxedema madness"), cerebellar signs, or somnolence may be present. Muscle relaxation times of the deep tendon reflexes are delayed markedly. (See Table 3.)

Laboratory Database. In addition to confirmatory serum TSH and free T4 levels, laboratory testing should include measurements of blood glucose, electrolytes, and arterial blood gases. Since treatment includes corticosteroid replacement, a serum cortisol should be obtained in suspected myxedema coma. Chest films, urinalysis, and blood cultures should be obtained for evidence of infection, which may be masked by the hypothermic state. Creatine kinase (CK-MM fraction) and serum glutamic oxaloacetic transaminase (SGOT/AST) elevations may demonstrate enzyme leakage or evidence of rhabdomyolysis. Arterial blood gases may need to be repeated at intervals due to insensitivity of the respiratory centers in the brain stem to hypoxia and hypercapnea, and to weakness of the intercostal and diaphragmatic muscles.31 Serum electrolytes, creatinine, blood urea nitrogen (BUN), and glucose should be monitored. Hyponatremia occurs in approximately 50% of severely hypothyroid patients, possibly related to decreased delivery of sodium and volume to the distal renal tubules as a result of decreased renal blood flow.1,19 Serum concentrations of atrial natriuretic peptide have been noted to be low, and may contribute to the hyponatremia.44

Treatment of Myxedema Coma. Thyroid hormone replacement is the definitive treatment for myxedema coma. Because this condition is rare and prospective, randomized controlled clinical trials are lacking; there is not uniform agreement as to the optimal dosage or form of replacement of thyroid hormone, which is most effective. Since hypotension and intestinal ileus are common, intravenous (IV) therapy is preferred. Levothyroxine (T3) has been given via nasogastric tube, but its bioavailability (50-80%) is unpredictable.31

Levothyroxine is the biologically active form, and levothyroxine (T4) is converted to T3 in vivo. Liothyronine is ideal for immediate thyroid hormone action, since it binds serum proteins to a lesser extent than levothyroxine, has a larger volume of distribution, and a shorter half-life. Intravenous liothyronine, marketed for parenteral administration as Triostat, is expensive and may be associated with increased mortality.45 Oral T3 is well absorbed even in a severely hypothyroid state.10 Both levothyroxine and liothyronine can be given alone or in combination, but levothyroxine alone often is recommended.1,10,29,39 Thyroxine-binding proteins have a large binding capacity, and it is necessary to saturate these proteins to provide an effective circulating level of T4. Conversely, rapid thyroid replacement runs a risk of inducing cardiac dysrhythmias, ischemia, and death. As discussed above, due to the adrenal hypofunction which accompanies severe hypothyroidism, it is important to give steroids when starting thyroid replacement therapy to avoid precipitating adrenal crisis.

It is important to note that T4 is highly protein bound. Only 0.02% is available as free T4, so it has a long biologic half-life of seven days. T3, the more active hormone, also is largely bound to plasma proteins, but at a lower affinity of 0.2% as free T3, so its biologic half-life is approximately one day. This explains the rationale of some authors for giving adequate T3 to patients in myxedema coma until they are able to generate T3 endogenously. After IV injection of T4, the T3 increases gradually. Since T3 has a much more rapid metabolic clearance and a small body pool, it cannot replete the body pool of thyroid hormone. The IV T4 preparation is in lyophilized form; an ampule contains 200 or 500 mcg. The IV T3 preparation is in a solution form containing 10 mcg in 1 mL solution, to be given every eight hours until the patient is conscious. Treatment guidelines are summarized in Table 4. There is evidence that high dose thyroid replacement of greater than 500 mcg/day of levothyroxine, or greater than 75 mcg/day of T3, may be associated with a high incidence of mortality.46

Treatment adjuncts include passive rewarming for hypothermia and maintenance of appropriate hydration status to address hyponatremia. (See Table 4.) Transfusion with packed red blood cells is appropriate if the hematocrit is below 20%. If hypotension is present, its pathogenesis may be multifactorial. Possible adrenal insufficiency should be addressed. Infectious sources should be sought and treated.29,47 Echocardiography should be performed to evaluate for evidence of pericardial effusion and global vs. regional hypokinesis.

General Treatment Recommendations in Myxedema Coma. First, confirm diagnosis of hypothyroidism in the ED with highly sensitive TSH and free T4 if rapidly available. Consider endocrinology consult prior to initiation of therapy in elderly hypothyroid patients or those with medical complexity. Full thyroid replacement can precipitate a myocardial infarction.29

Initiate treatment promptly if there is clinical evidence of myxedema coma; treatment should not await laboratory confirmation unless results are available rapidly. Aggressively address ventilatory, chemical, and vital sign abnormalities. Treatment of myxedema coma takes precedence over possible cardiac complications of therapy.

Hypotension should prompt a search for associated illness, including myocardial infarction or sepsis. Prophylactic antibiotics generally are not recommended. Cautious volume expansion should be tried initially. Dopamine may be preferable to other pressors because it better maintains coronary perfusion.10 Amrinone, an ino-vasodilator, may improve myocardial contractility because its mechanism of action does not depend on beta-receptors.15

Starting thyroid hormone replacement without also giving steroids (hydrocortisone) may precipitate adrenal crisis. Appropriate use of steroids also is important because thyroxine increases cortisol clearance.

If sodium values are below 120 mEq/L and there are significant mental status changes, isotonic or even hypertonic saline may be needed to raise levels to above 120 mEq/L.39,48 Asymptomatic hyponatremia can be monitored and usually resolves with l-thyroxine therapy.10 After establishment of adequate respiratory ventilation, thyroid hormone replacement, and care for the precipitating illness, patients should begin to show clinical improvement within the following 24-48 hours. Animal studies indicate that the earliest metabolic effects of T3 can be seen after 12-24 hours.39

Factors associated with poor outcome include advanced age, body temperature lower than 93°F, hypothermia persisting more than three days, bradycardia less than 44 beats/minute, hypotension, myocardial infarction, and sepsis.10,49

Elderly patients typically are stabilized at T4 dosing of 100-170 mcg/day, or 1.7 mcg/kg/day.

Admission Criteria for the Hypothyroid Patient. Table 5 summarizes suggested admission criteria. Although intensive care (ICU) criteria may vary by institution, specific vital sign abnormalities, including significant bradycardia, hypothermia, or clinical diagnosis of myxedema coma, warrant initiation of care in the ICU setting.

Hyperthyroidism

Background and Overview. The incidence of clinical and subclinical hyperthyroidism has been estimated to be 0.05-0.1%. Subclinical hyperthyroidism, as recognized by a subnormal TSH level, is seen in 0.2-5% of the elderly population, with less than 1% progression per year to overt disease.50,51

In older patients, the clinical expression of the hyperthyroid hypermetabolic state becomes blunted. Some researchers have proposed routine screening for thyroid disease in the elderly because the medical history and findings on physical examination become less sensitive and less specific for thyrotoxicosis. As well, treatment with medications such as beta-adrenergic blocking drugs and antianxiety medications also may blunt symptoms and signs of the hypermetabolic state. Many of the signs and symptoms of thyroid hormone excess described may have different manifestations in patients older than 60 years.5 Symptoms can be masked in apathetic hyperthyroidism.

Hyperthyroidism is an illness that can present a diagnostic challenge. For all practical purposes, the disease can be broken down into three categories: 1) sub-clinical or apathetic; 2) clinical hyperthyroid state; and 3) thyroid storm. Subclinical and apathetic hyperthyroidism both represent pathologic states not yet clinically evident with corresponding abnormal thyroid function. Clinical hyperthyroidism and thyroid storm, however, have signs and symptoms which may make the diagnosis evident clinically and which then can be confirmed with laboratory tests. Now that high sensitivity TSH assays commonly are available to emergency physicians, it is possible to make or confirm the diagnosis of hyperthyroidism in less obvious cases. In individuals without signs or symptoms, emergency treatment or admission generally is not required. The diagnosis of storm or hyperthyroid crisis, however, is critical because these patients invariably die without treatment.

Historically, thyroid storm was associated with surgery. Now with pre-treatment of hyperthyroidism prior to surgery, surgically related storm is rare; the majority of episodes are triggered by the stresses of medical illnesses. Graves’ disease accounts for the great majority of hyperthyroidism currently, followed by functionally autonomous (TSH-independent) multiple or solitary nodules.11 The exacerbation can be secondary to a known hyperthyroid state that is being treated, or an exacerbation of unknown, or apathetic, hyperthyroidism.

Symptoms and Signs of Thyrotoxicosis. This is a hypermetabolic state, and one of the common findings is excessive weight loss despite an unchanged or even increased caloric intake. It is notable that hyperthyroidism may present with a paucity of symptoms in the elderly, especially in patients older than 75 years. In older patients, weight loss may be the most common presenting complaint, with palpitations, weakness, dizziness and syncope following in that order.52 Alteration in mental status may be a presenting sign in the elderly, prompting a consideration of physical findings such as thyroid bruit. The American College of Emergency Physicians lists thyroid screening tests in its guidelines for the workup of the elderly patient with lethargy, agitation, or any alteration in level of consciousness.20 Weight loss results in depletion of fat stores and a decrease in muscle mass. Patients may complain of heat intolerance, with hyperhidrosis and flushing.5 They may have nonspecific symptoms of generalized weakness and a sense of fatigue resulting from changes both in their cardiorespiratory and neuromuscular systems. They may report nervousness or restlessness.

Apathetic thyrotoxicosis in the elderly is characterized by extreme fatigue, weakness, decreased activity, and emotional apathy.53 Tachycardia and thyromegaly may be absent. The patient is mentally slow and withdrawn. The skin is dry, coarse, cool, and wrinkled. There may be muscle wasting and proximal myopathy.53

Weakness in respiratory and skeletal muscles may be factors in decreased exercise tolerance and dyspnea. Decreased lung compliance and high output cardiac failure may contribute to shortness of breath.

Tracheal compression from an enlarged thyroid gland may cause shortness of breath, hoarseness, wheezing, and stridor. Pemberton’s sign is defined as inducing these dyspneic symptoms when patients are asked to raise their arms above their heads. Thyromegaly may cause wheezing, hoarseness, stridor, or dysphagia. A retrosternal thyroid in the elderly will not be palpable.

Vital signs classically include fever, with tachycardia out of proportion to the fever. However, these findings may be muted in the elderly, especially in patients on medications such as beta-blockers.

Gastrointestinal symptoms may be prominent. Dysphagia may be related to an enlarged thyroid gland that compresses the esophagus. Rapid intestinal transit time may cause increased bowel movement frequency. Nausea and vomiting occur frequently. Jaundice may be present, but is unusual.

Most patients with thyrotoxicosis have myopathy, which affects the proximal muscle groups of the shoulder and pelvic girdles more than distal muscles.54 Patients most often complain of difficulty standing up from a squatting position, or difficulty in climbing stairs.55 Muscle weakness resolves with therapy.

Many thyrotoxic patients complain of memory loss, confusional states, and short attention span. Unusual central nervous system (CNS) presentations include chorea, delirium, convulsions, stroke, cerebral venous thrombosis, and coma.5,54,56,57

Some psychiatric conditions may be mistaken for thyrotoxicosis. Patients may exhibit anxiety and restlessness. They may be emotionally labile or irritable. Speech and thought processing may be rapid. Dysphoric moods may be manifested by insomnia, phobias, delusions, vivid dreams, psychosis, and nightmares.3,58 (See Table 6.)

Physical Findings in the Hyperthyroid State. The skin may be flushed, with hyperhidrosis of the palms and soles. Hair may be fine and brittle; alopecia is common. Fever and tachycardia may be prominent.20

The orbitopathy of thyrotoxicosis is the result of contraction of the levator palpebrae superioris because of sympathetic hyperactivity. Measurable proptosis in Graves’ disease is caused by enlargement of the extraocular muscles. There may be lid lag, chemosis, exophthalmos, and vasodilatation of the conjunctiva with edema of the lids. Visual acuity may be compromised by compressive optic neuropathy.

Myxedema of the pretibial areas, feet, and toes is associated with autoimmune thyroid disease, and affects women more frequently than men. Raised pink or purple plaques are characteristic, with nonpitting edema.

Diffuse enlargement of the thyroid gland is characteristic of thyrotoxicosis from Graves’ disease, but it is infrequently palpable in patients older than 75 years of age.51 Elderly patients frequently have shrinking of the gland with age; as well, the thyroid may be substernal in the elderly.2 A bruit may be audible over the thyroid gland and is virtually diagnostic of Graves’ disease.5 One or more nodules palpable over the thyroid gland is suggestive of toxic adenoma or toxic multinodular goiter (Plummer’s disease). Patients with subacute thyroiditis may have tender thyroid glands.

Intestinal transit time is shortened, and abdominal pain or secretory diarrhea may be a presenting complaint.

Neuromuscular symptoms may be related to myopathy with proximal muscle weakness. Patients may exhibit muscle weakness, hyperactive reflexes, and tremor.59 Alterations in mental status may range from agitation to coma. The presence of myasthenia gravis in Graves’ hyperthyroidism is 0.35%, or 30 times that of the general population.3

Apathetic hyperthyroidism occurs frequently in advanced age, making the clinical diagnosis of hyperthyroidism in the elderly difficult. Symptoms such as tachycardia, weight loss, weakness, nervousness, palpitations, and heat intolerance, which make the diagnosis easier in younger patients, may be present only in a minority of older individuals.52 The diagnosis of apathetic hyperthyroidism frequently is made only during the work-up for atrial fibrillation, unexplained weight loss in the elderly, or worsening cardiovascular disease. Dementia and severe psychomotor retardation may be the most prominent findings.60

The Heart in Thyrotoxicosis. Thyrotoxicosis increases the work of the heart. Thyroid hormone can increase myocardial inotropy and heart rate and dilate peripheral arteries to increase cardiac output.61 Therefore, systemic vascular resistance is diminished, as is diastolic blood pressure.62 Most thyrotoxic patients report palpitations. A sense of irregular or rapid heartbeat becomes more apparent with increases in activity or exercise, eventually leading to decreased exercise tolerance.5,63 Dyspnea on exertion is common.

The pulse generally is bounding, with increased pulse pressure and elevated systolic blood pressure and a strong apical impulse. An increased myocardial oxygen demand as a result of the increased cardiac work of thyrotoxicosis may unmask previously unsuspected coronary artery disease. Sinus tachycardia and atrial fibrillation are common. Atrial arrhythmias frequently are accompanied by high output failure.64 In hyperthyroid patients older than 75 years, atrial fibrillation has been reported in 32-39% of cases.52,65 Anginal pain in the absence of coronary atherosclerosis may occur secondary to coronary artery spasm.66,67

ECG changes generally are nonspecific and may include shortening of the PR interval, or ST changes suggestive of myocardial ischemia or coronary spasm.62 Atrial fibrillation may be present.

Laboratory Testing. The diagnosis of hyperthyroidism generally requires testing for T4 and TSH. However, other tests may be applicable in the work-up of thyrotoxicosis and are worthy of mention.

Free thyroid hormone determinations are recommended for the assessment of thyroidal state. Both T4 and T3, which is mostly derived from the mono-deiodination in peripheral tissues of T4, are bound to the proteins thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin. Only 0.025% of T4 and 0.35% of T3 are free (non-protein bound). Since it is the free hormone that best correlates with the thyroidal state, the free T4 level—rather than the total T4 levels—is of most significance clinically. Furthermore, an increase in serum free T3 with normal free T4 estimate occurs in fewer than 5% of patients in North America (T3 thyrotoxicosis), so measurement of free T3 generally is unnecessary. Normal range for free T4 is 0.7-1.8 ng/dL. Free T3 reference levels are 1.5-3.5 pg/mL, but rarely are indicated in the emergency situation.15 It is notable that free T4 may be elevated with a normal TSH in patients taking levothyroxine for primary hypothyroidism, as well as in patients taking amiodarone.

Serum TSH also is required to diagnose hyperthyroidism. Assays for TSH now can distinguish levels in the normal range from those that are suppressed below the limits of assay sensitivity. Rarely, hyperthyroidism results from a TSH-secreting pituitary tumor. Suppressed TSH levels (< 0.05 mIU/mL) and increased serum free T4 estimates occur in approximately 95% of patients with clinically evident thyrotoxicosis.

While free T4 and TSH will suffice in the diagnostic work-up from the ED, a note on further testing is in order. Radioactive iodine uptake may be increased in the thyroid gland diffusely in Graves’ disease, or localized to thyroid nodules in toxic adenoma or multinodular goiter (Plummer’s disease). The erythrocyte sedimentation rate may be elevated markedly in patients with thyroid tenderness to palpation from subacute (viral) thyroiditis. Serum thyroglobulin is increased in thyroiditis. Since treatment of thyroid storm includes corticosteroids, a serum cortisol level prior to treatment should be obtained to document adrenal function.

Thyroid Storm. Thyroid storm is a life-threatening crisis of the hyperthyroid state characterized by decompensation of one or more organ systems.68 Exaggerated signs and symptoms of hyperthyroidism are present, characterized by fever, altered mental status, and cardiovascular dysfunction, usually with precipitating medical or surgical illness. Estimated mortality historically has been 20-30%.68 Historically, thyroid storm mainly was the result of thyroid surgery, although with preoperative treatment, thyrotoxic crisis has been caused more often by antecedent Graves’ disease, frequently with an identifiable precipitating event. Toxic multinodular goiter or toxic adenomas are less frequent causes for the hyperthyroid state.

Precipitants and Pathophysiology of Thyroid Storm. Precipitants include surgery, radioiodine therapy, iodinated contrast dyes, thyroid hormone ingestion, and a variety of medical emergencies, including diabetic ketoacidosis, cerebrovascular accident, pulmonary embolism, and congestive heart failure.69-72 (See Table 7.) Events that decompensate the hyperthyroid patient into thyroid storm must be identified and treated.39 Withdrawal or discontinuation of antithyroid medications may be causative, as well.

The specific mechanism by which thyroid storm occurs remains uncertain, and many theories have been proposed for the development of thyroid storm. The effects of acidosis or medical illness on thyroid hormone binding to carrier proteins have been proposed, resulting in higher levels of free hormone, possibly due to an acute decrease in thyroxine-binding globulin.39

Another theory proposes a role for enhanced adrenergic activity. There appears to be an exaggerated response to adrenergic stimuli, although levels of catecholamines do not seem to be higher in hospitalized patients with thyroid storm compared with other medically ill patients.4 Thyroid hormone increases the density of beta-adrenergic receptors, and appears to alter responsiveness to catecholamines at a postreceptor level.68 Therefore, the sensitivity of some tissues to catecholamines may be increased in some patients.

Diagnosis of Thyroid Storm. Thyroid storm is largely a clinical diagnosis. On physical examination, many of the stigmata of the hyperthyroid state may be present; for example, the exophthalmos, goiter, and widened pulse pressure of Graves’ disease. Thyrotoxic myopathy, with weakness of the proximal muscles, may occur. Fever, tachycardia, diaphoresis, and emotional lability may be present. Anorexia and crampy abdominal pain may be other gastrointestinal manifestations. Jaundice is a poor prognostic sign.

CNS disturbances occur in 90% of patients and range from restlessness, agitation, emotional lability, psychosis, and manic behavior to obtundation and coma. Status epilepticus and stroke may be presenting signs.

Nausea, vomiting, and diarrhea may contribute to dehydration. Atrial arrhythmias and ventricular tachyarrhythmias may complicate high output congestive heart failure.

It is critical for the emergency physician to diagnose storm or impending storm. Mortality when untreated is nearly 100%, but mortality with treatment has been reported to be 20-50%.73-75 Recently published data listed in-hospital mortality of 1.8% with aggressive therapy.76 While no uniform diagnostic criteria have been established to differentiate uncomplicated thyrotoxicosis from impending thyroid storm and established thyroid storm, Burch and Wartofsky have authored diagnostic criteria to diagnose impending thyroid storm.15,77 (See Table 8.)

Laboratory Diagnosis. Current recommendations include ordering a TSH and a free T4. Free T4 is elevated in 95% of hyperthyroid patients.78 Free T4 has not been shown to differentiate simple thyrotoxicosis from thyroid storm.79 TSH is highly sensitive, but its use alone is not recommended at this time.

A combination of low TSH and elevated free T4 makes the diagnosis. If TSH is lower than normal and free T4 is normal, free T3 testing is recommended. Free T3 will confirm the diagnosis of hyperthyroidism that results mostly from T3 secretion as well as providing a quantitative assessment of the hyperthyroid state, since T3 is the metabolically more active hormone. There is no indication for ED measurement of thyroglobulin or thyroid antibodies.5,78

Levels of circulating hormone may not be significantly different in thyroid storm from those seen in uncomplicated thyrotoxicosis. The clinical state may relate more to the rapidity with which thyroid hormone levels rise rather than with the absolute levels measured.

Thyroid storm involves multiple systems, and may be associated with lactic acidosis, evidence of liver dysfunction, rhabdomyolysis, and reversible cardiomyopathy.53

Treatment of Thyroid Storm. Treatment should address the following broad categories: supportive care, correction of the hyperthyroid state, managing the end organ effects of the syndrome, and diagnosis and treatment of the precipitating event. Specifically, thyroid hormone formation should be inhibited, release of hormone from the thyroid gland should be accomplished, and beta-adrenergic blockade provided.80 (See Table 9.) Dehydration and electrolyte imbalances should be addressed aggressively. Fever should be controlled with acetaminophen and additional cooling measures as needed. Since aspirin decreases protein binding and theoretically may increase free levels of T3 and T4, it should be avoided. Since thyrotoxic patients have accelerated degradation of cortisol, glucocorticoids should be administered to treat relative adrenal insufficiency.

Propylthiouracil (PTU) and methimazole (MMI) are thioamides, which block synthesis of thyroid hormone by inhibiting organification of tyrosine residues. The onset of action is within one hour, and peaks within weeks. These drugs inhibit synthesis of new thyroid hormone but do not affect the release of stored hormone. PTU has the additional benefit of inhibiting T4 to T3 conversion at high doses.81 It has been administered rectally, by retention enema when abdominal distention and hyperemesis were present.82-84

Iodide or lithium carbonate block release of preformed hormone within the gland. They should be given at least one hour after the loading dose of PTU or MMI. Otherwise, the iodide theoretically could increase intrathyroidal hormone stores by providing further substrate for hormone synthesis. The iodinated medications utilized include the oral contrast agents iopanoic acid (Telepaque) and ipodate (Oragrafin), Lugol’s iodine, and a saturated solution of potassium iodide (SSKI). Iopanoic acid and ipodate inhibit T4 to T3 conversion and have been considered the iodide preparations of choice.4,39 SSKI (5 drops every 6 hours) or Lugol’s solution (30 drops each day in 3-4 divided doses) are acceptable alternatives.13,85,86 Therapy with iodides may preclude future therapy with radioiodine for several months. SSKI has been administered sublingually and potassium iodide has been administered per rectum when emesis or small bowel obstruction has been present.82,83 When iodide is used in conjunction with the thioamides, serum T4 levels approach normal within 4-5 days.68

In patients who have a contraindication to iodide therapy, lithium has been used to inhibit thyroid hormone release. The usual dose is 300 mg every 6 hours orally or by nasogastric tube, adjusted to maintain serum lithium levels of approximately 1 mEq/L.59

Glucocorticoids at high doses may reduce conversion of T4 to T3. Use of glucocorticoids in thyroid storm is associated with improved survival rates.87,88 Administration of stress doses of corticosteroids is now routine, typically 100 mg hydrocortisone every 6-8 hours. There is a higher incidence of concomitant adrenal insufficiency in patients with Graves’ disease.

Blockade of peripheral thyroid hormone effects with beta-adrenergic blocking agents is the mainstay of treatment for thyroid storm. Oral propranolol has onset of action within one hour. For patients with contraindications to beta-blocker use, such as bronchospastic disease or heart block, a short-acting beta-blocker such as esmolol has been used safely.89 If beta-blockers are contraindicated absolutely, guanethidine 1-2 mg/kg/day in divided doses (30-40 mg orally every 6 hours), or reserpine (2.5-5 mg every 6 hours) may be considered.68,85,90

The serum half-life is six days for T4 and 22 hours for T3. Degradation of the circulating thyroid hormones must occur for complete resolution of the illness. The average duration of thyroid storm is three days, although the disease may take one week to resolve.

Thyroid Storm: Other Treatment Considerations. Adjunctive therapies for thyroid storm are listed in Table 10. Blood cultures, urinalysis, urine cultures, and chest radiography are routine to look for infection in thyroid storm.

Rarely, other treatment modalities have been employed to enhance the clearance of thyroid hormones. These include hemo-dialysis, peritoneal dialysis, charcoal hemoperfusion, exchange transfusion, plasmapheresis, and plasma exchange.91-93 Plasmapheresis has to be repeated several times, as only 20% of the T4 pool and even less of the T3 pool can be extracted per session.94

Side effects of the thionamides, PTU, and methimazole include allergic reactions, hepatotoxicity, and leukopenia/agranulocytosis. Most cases of agranulocytosis occur within three months of onset of treatment.95 It presents in the ED as fever and sore throat most commonly, although pneumonia and urinary tract infection may be present.96

Improvement in clinical status occurs over several days, although it may be 7-8 days before full recovery occurs, and a euthyroid state may not be achieved for 6-8 weeks.15 Mental status is a good clinical marker to monitor response to therapy.88

In thyrotoxicosis without storm, beta-blockers such as propranolol are considered the drugs of choice to reverse the tachycardia, widened pulse pressure, palpitations, and increased stroke volume that are present. Beta-adrenergic blockade is accompanied by improvement in tremulousness and heat intolerance, and is the treatment of choice for rate control for patients with atrial fibrillation.62 Calcium channel blockers have been used successfully to decrease the heart rate in patients with contraindications to beta-blocker use.97 Verapamil has been cited as the drug of choice.3

Rarely, patients may have severe hyperthyroidism in which iodine contamination is a difficult therapeutic problem. The most common cause for high iodine dosages in the elderly currently is amiodarone given to elderly cardiac patients.39 In such cases, perchlorate ions may have a role in treatment. Potassium perchlorate blocks the uptake of iodides by the thyroid cell. The recommended dose is 0.5 grams twice daily, given with propylthiouracil.80 Perchlorate has a high incidence of inducing bone marrow aplasias.

Antipyretic therapy should be with acetaminophen and not with salicylates, which displace thyroid hormone from thyroid binding proteins. (See Table 10.) Central thermal regulation, especially shivering, may be controlled with chlorpromazine (25-50 mg IV every 4-6 hours).80

Definitive ways of reducing thyroid hormone secretion include radioiodine and surgical ablation. The latter entails subtotal thyroidectomy and has fallen out of favor.11 Radioactive iodine, when it is trapped by hyperactive thyroid tissue, causes an intense radiation thyroiditis that leads to progressive fibrosis and glandular atrophy. The resulting destruction of the gland’s synthetic activity often causes hypothyroidism. Thionamides are prescribed to make the patient euthyroid prior to the administration of radioiodine.

Admission Criteria for the Hyperthyroid Elderly Patient. Suggested admission criteria are enumerated in Table 11. Many patients warrant hospitalization because of underlying cardiovascular, neurologic, or gastrointestinal manifestations, which would warrant hospitalization with or without thyroid disease. Any patient who meets the definition of thyroid storm warrants hospital admission.

Conclusions

Thyroid disease may present atypically in the elderly. The absence of the full constellation of symptoms, characteristic in a younger population, may make the clinical diagnosis elusive. Symptoms also may be masked by medications the patient may be taking for unrelated disease. Development of unstable illness, especially cardiac disease, is a frequent mode of presentation. In the elderly, there may be merit in screening for thyroid disease.89

References

1. Myers L, Hays J. Myxedema coma. Crit Care Clin 1991;7:43-56.

2. Mintzer MJ. Hypothyroidism and hyperthyroidism in the elderly. J Fla Med Assn 1992;79:231-235.

3. Kannan CR, Seshari KG. Thyrotoxicosis. Dis Mon 1997;43:601-677.

4. Ringel MD. Management of hypothyroidism and hyperthyroidism in the intensive care unit. Crit Care Clin 2001;17:59-74.

5. Dabon-Almirante CL, Surks MI. Clinical and laboratory diagnosis of thyrotoxicosis. Endocrinol Metab Clin 1998;27:26-35.

6. Hamilton MA, Stevenson LW, Luu M, et al. Altered thyroid hormone metabolism in advanced heart failure. J Am Coll Cardiol 1990;16:91-95.

7. Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: The Whickham survey. Clinical Endocrinol (Oxf) 1977;7: 481-493.

8. Bagchi N, Brown TR, Parish RF. Thyroid dysfunction in adults over 55 years. Arch Int Med 1990;150:785-787.

9. Sawin CT, Castelli WP, Hershman JM, et al. The aging thyroid: Thyroid deficiency in the Framingham study. Arch Intern Med 1985;145:1386-1388.

10. Jordan RM. Myxedema coma. Med Clin North Am 1995;79:185-194.

11. Wartofsky L. Treatment options for hyperthyroidism. Hosp Pract 1996;31: 69-84.

12. Wartofsky L. Myxedema coma. In: Braverman LE, Utiger RD (eds). The Thyroid. Philadelphia: JB Lippincott; 1996:871-877.

13. Hurley DL, Gharib H. Detection and treatment of hypothyroidism and Graves’ disease. Geriatrics 1995;50:41-44.

14. Robuschi G, Safran M, Braverman LE, et al. Hypothyroidism in the elderly. Endocr Rev 1987;8:142-153.

15. Wall RT. Unusual endocrine problems. Anesthesiol Clin North Am 1996;14:471-493.

16. Bailes BK. Hypothyroidism in elderly patients. AORN J 1999;69:1026-1030.

17. Talbot-Stern JK, Green T, Royle TJ. Psychiatric manifestations of systemic illness. Emerg Med Clin North Am 2000;18:199-210.

18. Surks MI, Ocampo E. Subclinical thyroid disease. Am J Med 1996; 100: 217-223.

19. Forester CF. Coma in myxedema. Arch Intern Med 1963;111:100.

20. American College of Emergency Physicians. Clinical policy for the initial approach to patients presenting with altered mental status. Ann Emerg Med 1999;33:251-281.

21. Olsen CG. Myxedema coma in the elderly. J Am Board of Fam Pract 1995; 8:376-383.

22. Kumar A, Bhandari AK, Rahimtoola SH. Torsades de pointes and marked QT prolongation in association with hypothyroidism. Ann Intern Med 1987; 106:712-714.

23. Guthrie GP Jr, Hunsaker JC III, O’Connor WN. Sudden death in hypothyroidism. N Engl J Med 1987;317:1291.

24. Khaleeli AA, Memon N. Factors affecting resolution of pericardial effusions in primary hypothyroidism: A clinical, biochemical and echocardiographic study. Postgrad Med 1982;58:473-476.

25. Urbanic RC, Mazzaferri EL. Thyrotoxic crisis and myxedema coma. Heart Lung 1978;7:435.

26. Singer PA, Cooper DS, Levy EG, et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. JAMA 1995;273:808-812.

27. U. S. Preventive Services Task Force, Guidelines From Guide to Clinical Preventive Services, (2nd ed.). Philadelphia: Williams & Wilkins; 1996: 1-11.

28. Orija IB, Cohen SB. An elderly woman with drug-induced coma in winter. Cleve Clin J Med 2001;68:25-32.

29. Nicoloff JT, LoPresti JS. Myexedema coma: Myxedema coma. Endocrinol Metab Clin North Am 1993;22:279-289.

30. Cohen LF, Mohabeer AJ, Keffer JH, et al. Troponin I in hypothyroidism. Clin Chem 1996;42:1494-1495.

31. Pittman CS, Zayed AA. Myxedema coma. Curr Ther Endocrinol Metab 1997;6:98-101.

32. Davis PJ, Davis FB. Hypothyroidism in the elderly. Compr Ther 1984;10: 17-23.

33. Reinhardt W, Mann K. Incidence, clinical picture and treatment of hypothyroid coma. Medizinische Klinik 1997;92:521-524.

34. Wall CR. Myxedema coma: Diagnosis and treatment. Am Fam Physician 2000;62:2485-2490.

35. Werner SC, Ingbar SH, Braverman LE, et al. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text (8th ed.). Philadelphia: Lippincott Williams & Wilkins: 2000.

36. Ingmar SH, Braverman LE. The Thyroid: A Fundamental and Clinical Text. Philadelphia: Lippincott, Williams & Wilkins; 1986:1227-1233.

37. Santiago R, Rashkin MC. Lithium toxicity and myxedema coma in an elderly woman. J Emerg Med 1990:8:63.

38. Mazonson PD, Williams ML, Cantley LK, et al. Myxedema coma during long term amiodarone therapy. Am J Med 1984;77:751.

39. Burger AG, Philippe J. Thyroid emergencies. Baillieres Clinical Endocrin-ology and Metabolism 1992;6:77-93.

40. Massumi RA, Winnacker JL. Severe respiratory depression of the respiratory center in myxedema. Am J Med 1964;36:876.

41. Zwillich CW, Pierson DJ, Hofeldt FD, et al. Ventilatory control in myxedema and hypothyroidism. N Engl J Med 1975;292:662.

42. Klein I. Thyroid hormone and blood pressure regulation. In: Laragh JH, Brenner BM, Kaplan NM, eds. Endocrine Mechanisms in Hypertension, Vol. 2. New York: Raven Press; 1989:1661-1674.

43. Patel R, Hughes RW Jr. An unusual case of myxedema megacolon with features of ischemic and pseudomembranous colitis. Mayo Clin Proc 1992;67: 369-372.

44. Zimmerman RS, Gharib H, Zimmerman D, et al. Atrial natriuretic peptide in hypothyroidism. J Clin Endocrinol Metab 1987;64:353-355.

45. Hylander B, Rosenquist U. Treatment of myxedema coma—Factors associated with a fatal outcome. Acta Endocrinol 1985;180:65.

46. Yamamoto T, Fukuyama J, Fujiyoshi A. Factors associated with mortality of myxedema coma: Report of eight cases and literature survey. Thyroid 1999;9:1167-1174.

47. Lindberger K. Myxedema coma. Acta Med Scand 1975;198:87.

48. Senior RM, Birge SJ, Wessler S, et al. The recognition and management of myxedema coma. JAMA 1971;217:61.

49. Arlot S, Debussche X, Lalaw JD et al. Myxedema coma: Response of thyroid hormone with oral and intravenous high-dose l-thyroxine treatment. Intens Care Med 1991;19:16.

50. Sawin CT, Geller A, Kaplan MM, et al. Low serum thyrotropin (TSH) in older persons without hyperthyroidism. Arch Intern Med 1991;151:165-168.

51. Sundbeck G, Lundberg P-A, Lindstendt G, et al. Incidence and prevalence of thyroid disease in elderly women: Results from the longitudinal population study of elderly people in Gothenburg, Sweden. Age Aging 1991;20: 291-298.

52. Tibaldi JM, Barzel U, Albin J, et al. Thyrotoxicosis in the very old. Am J Med 1986;81:619-622.

53. Jiang YZ, Hutchinson KA, Bartelloni P, et al. Thyroid storm presenting as multiple organ dysfunction syndrome. Chest 2000;118:877-879.

54. Logothetic L. Neurologic and muscular manifestations of hyperthyroidism. Arch Neurol 1961;5:533-544.

55. Engel A. Neuromuscular manifestations of Graves’ disease. Mayo Clin Proc 1972;47:919-925.

56. Verberne HJ, Fliers E, Prummel MF, et al. Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis. Thyroid 2000;10:607-610.

57. Lee TG, Ha CK, Lim BH. Thyroid storm presenting as status epilepticus and stroke (letter). Postgrad Med J 1997;73:61.

58 Thomas F, Mazzaferri EL, Skillman TG. Apathetic thyrotoxicosis: A distinctive clinical and laboratory entity. Ann Intern Med 1970;72:679-685.

59. Smallridge RC. Metabolic and anatomic thyroid emergencies: A review. Crit Care Med 1992;20:276-291.

60. Talbot-Stern JK, Green T, Royle TJ. Psychiatric manifestations of systemic illness. Emerg Med Clin North Am 2000;18:199-210.

61. Gomberg-Maitland M, Frishman WH. Thyroid hormone and cardiovascular disease. Am Heart J 1998;135:187-196.

62. Klein I, Ojamaa K. Thyrotoxicosis and the heart. Endocrin Metabol Clin 1998;27:51-62.

63. Drinka PJ, Nolten WE. The prevalence of previously undiagnosed hypothyroidism in residents of a midwestern nursing home. South Med J 1990;83: 1259-1261.

64. Woeber KA. Thyrotoxicosis and the heart. N Engl J Med 1992;327:94-98.

65. Davis PJ, Davis FB. Hyperthyroidism in patients over the age of 60 years. Medicine 1974;53:161-180.

66. Moliterno D, DeBold CR, Robertson RM. Case report: Coronary vaso-spasm: Relation to the hyperthyroid state. Am J Med Sci 1992;304:38-42.

67. Rowe GG, Huston JH, Weinstein AB, et al. The hemodynamics of thyrotoxicosis in man with special reference to coronary blood flow and myocardial oxygen metabolism. J Clin Invest 1956;35:272-276.

68. Tietgens ST, Leinung MC. Thyroid storm. Med Clin North Am 1995;79: 169-184.

69. Yoshida D. Thyroid storm precipitated by trauma. J Emerg Med, 1996;14: 697-701.

70. Georges JL, Normand JP, Lenormand ME, et al. Life-threatening thyrotoxicosis induced by amiodarone in patients with benign heart disease. Euro Heart J 1992;13:129-132.

71. Samaras K, Marel GM. Failure of plasmapheresis, corticosteroids, and thionamides to ameliorate a case of protracted amiodarone-induced thyroiditis. Clin Endocrinol 1996;45:365-368.

72. Wilson BE, Hobbs WN. Case report: Pseudoephedrine-associated thyroid storm: Thyroid hormone-catecholamine interactions. Am J Med Sci 1993; 306:317-319.

73. Lahey FH. The crisis of exophthalmic goiter. N Engl J Med 1928;199: 255-257.

74. Ashkar FS, Miller R, Gibson AJ. Thyroid function and serum thyroxine in thyroid storm. South Med J 1972;65:372-374

75. Mazzaferri E, Skillman T. Thyroid storm: Review of 22 episodes with special emphasis on the use of guanethidine. Arch Intern Med 1969;124:684-690.

76. Sherman SI, Simons L, Ladenson PW. Clinical and socioeconomic predispositions to complicated thyrotoxicosis: A predictable and preventable outcome? Am J Med 1996;101:192.

77. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis, thyroid storm. Endocrinol Metab Clin North Am 1993;22:263-277.

78. Surks M, Chopra IJ, Mariash CN, et al. American Thyroid Association Guidelines for Use of Laboratory Tests in Thyroid Disorders. JAMA 1990; 263:1529-1532.

79. Brooks MH, Waldstein SS. Free thyroxine concentrations in thyroid storm. Ann Intern Med 1980;93:694-697.

80. Dillman WH. Thyroid storm. Curr Ther Endocrinol Metab 1997;6:81-85.

81. Geffner DL, Azukizawa M, Hershman JM. Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man. J Clin Invest 1975;55:224-229.

82. Yeung SC, Go R, Balasubramanyam A. Rectal administration of iodide and propylthiouracil in the treatment of thyroid storm. Thyroid 1995;5:403-405.

83. Cansler CL, Latham JA, Brown PM Jr, et al. Duodenal obstruction in thyroid storm. South Med J 1997;90:1142-1146.

84. Walter RM Jr, Bartle WR. Rectal administration of propyl thiouracil in the treatment of Graves’ disease. Am J Med 1990;88:69-70.

85. Waldstein SS, Slodki SJ, Kaganiec GL, et al. A clinical study of thyroid storm. Ann Intern Med 1960;52:626-642.

86. Mackin JF, Canary JJ, Pittman CS. Thyroid storm and its management. N Engl J Med 1974;291:1396-1398.

87. Ngbar SH. Management of medical emergencies IX. Thyroid storm. N Engl J Med 1966;274:1252-1254.

88. Mazzaferri EL, Surks MI. Recognizing the faces of hypothyroidism. Hospital Practice (office ed.) 1999;34:109-110.

89. Brunette DD, Rothong C. Emergency department management of thyrotoxic crisis with esmolol. Am J Emerg Med 1991;9:232-234.

90. Wartofsky L. Thyrotoxic Storm. In: Braverman LE, Utiger RD (eds), The Thyroid. Philadelphia: JB Lippincott; 1996:701-707.

91. Candrina R, DiStefano O, Spandrio S, et al. Treatment of thyrotoxic storm by charcoal plasmaperfusion. J Endocrinol Invest 1989;12:133-134.

92. Ashkar FS, Katims RB, Smoak WM III, et al. Thyroid storm treatment with blood exchange and plasmapheresis. JAMA 1970;214:1275-1279.

93. Tajiri J, Katsuya H, Kiyokawa T, et al. Successful treatment of thyrotoxic crisis with plasma exchange. Crit Care Med 1984;12:536-537.

94. Segers O, Spapen H, Steenssens L, et al. Treatment of severe iodine-induced hyperthyroidism with plasmapheresis. Acta Clinica Belgica 1988;43:335-343.

95. Cooper DS, Goldminz D, Levin AA, et al. Agranulocytosis associated with anti-thyroid drugs: Effects of patient age and drug dose. Ann Intern Med 1983;98:26-29.

96. Sheng WH, Hung CC, Chen YC, et al. Antithyroid drug-induced agranulocytosis complicated by life-threatening infections. QJM 1999;92:455-461.

97. Valcavi R, Menozi C, Roti E, et al. Sinus node function in hyperthyroid patients. J Clin Endocrinol Metab 1992;75:239.

98. Santiago R, Rashkin MC. Lithium toxicity and myxedema coma in an elderly woman. J Emerg Med 1990;8:63-66.


CME Objectives

Upon completing this program, participants will be able to:

• Quickly recognize or increase index of suspicion for specific conditions in the elderly patient;

• Understand the epidemiology, etiology, pathophysiology, and clinical features of the entity discussed;

• Perform necessary diagnostic tests correctly and take a meaningful patient history that will reveal the most important details about the particular medical problem discussed;

• Apply state-of-the-art therapeutic techniques (including the implications of the pharmaceutical therapy discussed) to patients with the particular medical problem discussed; and

• Provide patients with any necessary discharge instructions.

Physician CME Questions

1. Factors in the medical history that may precipitate hypothyroid crisis include:

A. previous thyroid surgery.

B. congestive heart failure.

C. use of sedatives or narcotics.

D. hypothermia or cold exposure.

E. All of the above


2. The typical group presenting with myxedema coma is:

A. elderly women.

B. elderly men.

C. children.

D. adolescents.

E. No group presents more often than others.


3. Currently, the most common cause of thyroid storm is:

A. thyroid surgery.

B. Graves’ disease.

C. functionally autonomous multiple or solitary nodules.

D. toxemia of pregnancy.


4. Estimated mortality associated with thyroid storm historically has been:

A. 0-5%.

B. 5-15%.

C. 20-30%.

D. greater than 50%.


5. Ninety-five percent of thyroid storm patients will have elevated levels of:

A. free T4.

B. TSH.

C. epinephrine.

D. All of the above


6. To reverse tachycardia, widened pulse pressure, palpitations, and increased stroke volume in thyrotoxicosis without storm, beta-blockers are considered the drugs of choice.

A True

B. False


7. Treatment of thyroid storm should include:

A. hormone synthesis blockade.

B. inhibition of hormone release.

C. glucocorticoids.

D. adrenergic blockade.

E. All of the above


8. Fever in severe hyperthyroidism should be treated with:

A. aspirin.

B. acetaminophen.

C. Either A or B