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Thyroid and heart diseases. A relation between the thyroid and the heart has long been recognized. A relation between the thyroid and the heart has long.

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Presentation on theme: "Thyroid and heart diseases. A relation between the thyroid and the heart has long been recognized. A relation between the thyroid and the heart has long."— Presentation transcript:

1 Thyroid and heart diseases

2 A relation between the thyroid and the heart has long been recognized. A relation between the thyroid and the heart has long been recognized. In the late 1700s, a patient with clinical features of thyrotoxicosis including palpitations, irregular pulse, and dyspnea was described. In the late 1700s, a patient with clinical features of thyrotoxicosis including palpitations, irregular pulse, and dyspnea was described. In the early 1900s, a patient with “myxedema heart” was reported: The critical findings were enlarged cardiac silhouette, low electrocardiographic voltage, and bradycardia. In the early 1900s, a patient with “myxedema heart” was reported: The critical findings were enlarged cardiac silhouette, low electrocardiographic voltage, and bradycardia.

3 Thyroxine (T4), is the major secretory product of the thyroid gland. Triiodothyronine (T3), the biologically active compound, is in large part derived from peripheral conversion of T4 by the 5'-monodeiodinase enzyme. Thyroxine (T4), is the major secretory product of the thyroid gland. Triiodothyronine (T3), the biologically active compound, is in large part derived from peripheral conversion of T4 by the 5'-monodeiodinase enzyme. Cardiovascular manifestations are frequent in thyroid dysfunction and may be the result of Cardiovascular manifestations are frequent in thyroid dysfunction and may be the result of direct hormone effects at the cellular level, direct hormone effects at the cellular level, interactions with the sympathetic nervous system, or interactions with the sympathetic nervous system, or alterations of peripheral circulation and metabolism. alterations of peripheral circulation and metabolism. At the cellular level, thyroid hormones act mainly through binding to specific nuclear receptors and activation of gene transcription. Additionally, they activate extranuclear sites as mitochondrial and membrane-bound enzymes. At the cellular level, thyroid hormones act mainly through binding to specific nuclear receptors and activation of gene transcription. Additionally, they activate extranuclear sites as mitochondrial and membrane-bound enzymes.

4 Hyperthyroidism Hyperthyroidism is the clinical state resulting from excess production of T4, T3 or both. Hyperthyroidism is the clinical state resulting from excess production of T4, T3 or both. The most common cause is a diffuse toxic goiter (Graves disease). Although the etiology of this condition is still unknown, the hyperproduction of T4 and T3 is thought to result from circulating IgG autoantibodies that bind to the thyrotropin receptor on the thyroid gland. The most common cause is a diffuse toxic goiter (Graves disease). Although the etiology of this condition is still unknown, the hyperproduction of T4 and T3 is thought to result from circulating IgG autoantibodies that bind to the thyrotropin receptor on the thyroid gland. The second most common form of hyperthyroidism is nodular toxic goiter, a condition in which localized areas of the gland function excessively and autonomously. The second most common form of hyperthyroidism is nodular toxic goiter, a condition in which localized areas of the gland function excessively and autonomously.

5 Hyperthyroidism is a relatively common disease that occurs four to eight times more often in women than men, with a peak incidence in the third and fourth decades. Hyperthyroidism is a relatively common disease that occurs four to eight times more often in women than men, with a peak incidence in the third and fourth decades. signs and symptoms include signs and symptoms include fatigue, hyperactivity, insomnia, heat intolerance, palpitations, dyspnea, increased appetite with weight loss, nocturia, diarrhea, oligomenorrhea, muscle weakness, tremor, emotional lability, increased heart rate, systolic hypertension, hyperthermia, warm moist skin, lid lag, stare, and brisk reflexes. Serum T4 levels are increased and serum TSH is suppressed fatigue, hyperactivity, insomnia, heat intolerance, palpitations, dyspnea, increased appetite with weight loss, nocturia, diarrhea, oligomenorrhea, muscle weakness, tremor, emotional lability, increased heart rate, systolic hypertension, hyperthermia, warm moist skin, lid lag, stare, and brisk reflexes. Serum T4 levels are increased and serum TSH is suppressed

6 CARDIOVASCULAR MANIFESTATIONS. Palpitations, dyspnea, tachycardia, and systolic hypertension are common findings. Diastolic hypertension can also occur. Palpitations, dyspnea, tachycardia, and systolic hypertension are common findings. Diastolic hypertension can also occur. Typically noted are a hyperactive precordium with Typically noted are a hyperactive precordium with a loud first heart sound, a loud first heart sound, an accentuated pulmonic component of the second heart sound, and an accentuated pulmonic component of the second heart sound, and a third heart sound;. a third heart sound;.

7 It has been suggested that many of the changes in cardiac function are secondary to the increased metabolic demands of peripheral tissue. It has been suggested that many of the changes in cardiac function are secondary to the increased metabolic demands of peripheral tissue. also thyroid hormone exerts a direct cardiac stimulant action independent of its effect on general tissue metabolism,.as, normalization of the myocardial contractile response to exercise may not occur until several months after normalization of thyroid function. also thyroid hormone exerts a direct cardiac stimulant action independent of its effect on general tissue metabolism,.as, normalization of the myocardial contractile response to exercise may not occur until several months after normalization of thyroid function.

8 Roentgenographic and electrographic changes, are nonspecific in hyperthyroidism. Thus, on chest x-ray the left ventricle, aorta, and pulmonary artery are prominent, and in some cases, generalized cardiac enlargement can be noted. are nonspecific in hyperthyroidism. Thus, on chest x-ray the left ventricle, aorta, and pulmonary artery are prominent, and in some cases, generalized cardiac enlargement can be noted. In patients with sinus rhythm, the magnitude of the tachycardia in general parallels the severity of the disease. In patients with sinus rhythm, the magnitude of the tachycardia in general parallels the severity of the disease. Sinus tachycardia is present in 40 percent of patients with hyperthyroidism and occurs most frequently in the younger age groups and often at night Sinus tachycardia is present in 40 percent of patients with hyperthyroidism and occurs most frequently in the younger age groups and often at night

9 ten to 15 percent of patients with hyperthyroidism have persistent atrial fibrillation, which is often heralded by one or more transient episodes of this arrhythmia ten to 15 percent of patients with hyperthyroidism have persistent atrial fibrillation, which is often heralded by one or more transient episodes of this arrhythmia Intraatrial conduction disturbances, manifested by prolongation or notching of the P wave and, occur in 15 and 5 percent of patients with hyperthyroidism, respectively. Intraatrial conduction disturbances, manifested by prolongation or notching of the P wave and, occur in 15 and 5 percent of patients with hyperthyroidism, respectively. Occasionally, second- or third-degree heart block may result. The cause of the AV conduction disturbance is not clear Occasionally, second- or third-degree heart block may result. The cause of the AV conduction disturbance is not clear

10 Intraventricular conduction disturbances, most commonly right bundle branch block, occur in about 15 percent of patients with hyperthyroidism without associated heart disease of other etiology Intraventricular conduction disturbances, most commonly right bundle branch block, occur in about 15 percent of patients with hyperthyroidism without associated heart disease of other etiology Paroxysmal supraventricular tachycardia and flutter are rare in hyperthyroidism. Paroxysmal supraventricular tachycardia and flutter are rare in hyperthyroidism. Finally, occult thyrotoxicosis may underlie either chronic or paroxysmal isolated atrial fibrillation Finally, occult thyrotoxicosis may underlie either chronic or paroxysmal isolated atrial fibrillation

11 In most instances the development of clinical manifestations of heart failure and myocardial ischemia in patients with hyperthyroidism signifies the presence of underlying cardiac or coronary vascular disease. In most instances the development of clinical manifestations of heart failure and myocardial ischemia in patients with hyperthyroidism signifies the presence of underlying cardiac or coronary vascular disease. Both angina pectoris and heart failure occur in patients with hyperthyroidism. Both angina pectoris and heart failure occur in patients with hyperthyroidism. For many years it was assumed that these conditions were seen only in the presence of underlying cardiovascular disease. For many years it was assumed that these conditions were seen only in the presence of underlying cardiovascular disease.

12 More recently, however, lines of evidence have suggested otherwise: More recently, however, lines of evidence have suggested otherwise: (1) Congestive heart failure has been produced in experimental animals by simply administering T4. (1) Congestive heart failure has been produced in experimental animals by simply administering T4. (2) Congestive heart failure may develop in children with thyrotoxicosis and no underlying cardiac disease. (2) Congestive heart failure may develop in children with thyrotoxicosis and no underlying cardiac disease. (3) Angina has been reported in a hyperthyroid patient with normal coronary arteries, presumably secondary to thyroid- induced coronary artery spasm. (3) Angina has been reported in a hyperthyroid patient with normal coronary arteries, presumably secondary to thyroid- induced coronary artery spasm. (4) The abnormal left ventricular function observed during exercise in hyperthyroid subjects is not reversed by beta blockade but is reversed by treating the hyperthyroidism. (4) The abnormal left ventricular function observed during exercise in hyperthyroid subjects is not reversed by beta blockade but is reversed by treating the hyperthyroidism.

13 The frequency of hyperthyroidism is also increased in patients with familial hypertrophic cardiomyopathy. The frequency of hyperthyroidism is also increased in patients with familial hypertrophic cardiomyopathy. Finally, hyperthyroidism is associated with mitral value prolapse in more than a third of cases. Finally, hyperthyroidism is associated with mitral value prolapse in more than a third of cases.

14 DIAGNOSIS AND TREATMENT OF HYPERTHYROIDISM The diagnosis is confirmed with a low TSH level, which reflects an elevated level of thyroid hormone in the blood. The diagnosis is confirmed with a low TSH level, which reflects an elevated level of thyroid hormone in the blood. In elderly patients with hyperthyroidism, cardiovascular manifestations predominate, specifically, atrial fibrillation and/or congestive heart failure, and therefore evaluation of thyroid function in such patients is particularly important. In elderly patients with hyperthyroidism, cardiovascular manifestations predominate, specifically, atrial fibrillation and/or congestive heart failure, and therefore evaluation of thyroid function in such patients is particularly important. Definitive treatment of hyperthyroidism is surgical removal of the gland or irradiation with radioactive iodide. Definitive treatment of hyperthyroidism is surgical removal of the gland or irradiation with radioactive iodide.

15 In severely ill patients, particularly those with thyroid storm, significant cardiovascular symptoms, or both, neither of these therapies is appropriate. In severely ill patients, particularly those with thyroid storm, significant cardiovascular symptoms, or both, neither of these therapies is appropriate. Thus, medical therapy is directed at reducing both the production and the biological effect of thyroid hormone with thionamides and beta blockers. Thus, medical therapy is directed at reducing both the production and the biological effect of thyroid hormone with thionamides and beta blockers. Tachycardia, palpitations, tremor, restlessness, muscle weakness, and heat intolerance are reversed by these agents, which offer the additional benefit of inhibiting the conversion of T4 to the biologically active T3 in peripheral tissues. Tachycardia, palpitations, tremor, restlessness, muscle weakness, and heat intolerance are reversed by these agents, which offer the additional benefit of inhibiting the conversion of T4 to the biologically active T3 in peripheral tissues.

16 TREATMENT OF CARDIOVASCULAR MANIFESTATIONS OF HYPERTHYROIDISM. Prompt treatment of hyperthyroidism can significantly reduce, if not eliminate the associated cardiovascular symptoms. Prompt treatment of hyperthyroidism can significantly reduce, if not eliminate the associated cardiovascular symptoms. About half of patients with concurrent onset of hyperthyroidism and angina pectoris experience complete remission of this symptom after treatment of hyperthyroidism About half of patients with concurrent onset of hyperthyroidism and angina pectoris experience complete remission of this symptom after treatment of hyperthyroidism Furthermore, in 30 to 40 percent of thyrotoxic patients with atrial fibrillation sustained for 1 week or longer, spontaneous reversion to sinus rhythm occurs when they become euthyroid. Furthermore, in 30 to 40 percent of thyrotoxic patients with atrial fibrillation sustained for 1 week or longer, spontaneous reversion to sinus rhythm occurs when they become euthyroid.

17 Beta-blocking drugs also control the ventricular rate in atrial fibrillation. Beta-blocking drugs also control the ventricular rate in atrial fibrillation. The most useful agents for correcting the fundamental defect are thionamides such as propylthiouracil, which inhibits thyroid hormone synthesis. The most useful agents for correcting the fundamental defect are thionamides such as propylthiouracil, which inhibits thyroid hormone synthesis. Iodine inhibits the release of thyroid hormones from the thyrotoxic gland, and its beneficial effects occur more rapidly than those of thionamides. It is therefore useful for rapid amelioration of the hyperthyroid state in patients with thyroid heart disease Iodine inhibits the release of thyroid hormones from the thyrotoxic gland, and its beneficial effects occur more rapidly than those of thionamides. It is therefore useful for rapid amelioration of the hyperthyroid state in patients with thyroid heart disease The nonselective agent propranolol has been traditionally used, but selective beta1-adrenergic antagonists such as atenolol appear equally effective. The nonselective agent propranolol has been traditionally used, but selective beta1-adrenergic antagonists such as atenolol appear equally effective.

18 If beta-blockers are contraindicated, calcium channel blockers such as verapamil or diltiazem can be administered as negative chronotropic agent. However, caution is warranted, as these agents may lead to hemodynamic instability by further reducing systemic vascular resistance and contractility. If beta-blockers are contraindicated, calcium channel blockers such as verapamil or diltiazem can be administered as negative chronotropic agent. However, caution is warranted, as these agents may lead to hemodynamic instability by further reducing systemic vascular resistance and contractility. Hyperthyroid patients with cardiovascular disease are particularly resistant to therapy. It has been well documented that both heart failure and arrhythmias are resistant to conventional doses of cardiac glycosides., serum levels of cardiac glycosides are diminished in hyperthyroidism, because its metabolism is increased, toxicity may develop at a dose that has relatively little therapeutic effect. Hyperthyroid patients with cardiovascular disease are particularly resistant to therapy. It has been well documented that both heart failure and arrhythmias are resistant to conventional doses of cardiac glycosides., serum levels of cardiac glycosides are diminished in hyperthyroidism, because its metabolism is increased, toxicity may develop at a dose that has relatively little therapeutic effect.

19 Hypothyroidism Hypothyroidism is the clinical syndrome associated with decreased secretion of thyroid hormones. This condition reflects in over 90% of cases a disease of the gland itself (primary hypothyroidism). Rarely, hypothyroidism can be caused by pituitary disease (secondary hypothyroidism) or hypothalamic disease (tertiary hypothyroidism). Hypothyroidism is the clinical syndrome associated with decreased secretion of thyroid hormones. This condition reflects in over 90% of cases a disease of the gland itself (primary hypothyroidism). Rarely, hypothyroidism can be caused by pituitary disease (secondary hypothyroidism) or hypothalamic disease (tertiary hypothyroidism). The most frequent cause of hypothyroidism in adults is autoimmune thyroiditis, or Hashimoto’s disease. Accordingly, women are more frequently affected. The most frequent cause of hypothyroidism in adults is autoimmune thyroiditis, or Hashimoto’s disease. Accordingly, women are more frequently affected.

20 clinical manifestations, clinical manifestations, dry skin, weight gain, fatigue, and forgetfulness, Other complaints of hypothyroid patients include increased tiredness and sleep requirement, depressed mood, cold intolerance, constipation, and decreased exercise tolerance. Pleural effusions and pitting edema may occur in absence of heart failure. dry skin, weight gain, fatigue, and forgetfulness, Other complaints of hypothyroid patients include increased tiredness and sleep requirement, depressed mood, cold intolerance, constipation, and decreased exercise tolerance. Pleural effusions and pitting edema may occur in absence of heart failure.

21 Cardiovascular Involvement Bradycardia is common, and Bradycardia is common, and pericardial effusion may occur in up to one-half of patients but rarely causes hemodynamic compromise. pericardial effusion may occur in up to one-half of patients but rarely causes hemodynamic compromise. Both diastolic and systolic LV performance may be decreased, presumably because of alterations in calcium uptake and release by cardiac myocytes. Additionally, Both diastolic and systolic LV performance may be decreased, presumably because of alterations in calcium uptake and release by cardiac myocytes. Additionally, an increase in systemic vascular resistance is observed, possibly as the result of the lack of direct vasodilatory effect of thyroid hormones. an increase in systemic vascular resistance is observed, possibly as the result of the lack of direct vasodilatory effect of thyroid hormones. The resulting hemodynamic changes are opposite but less marked than with thyrotoxicosis. Characteristic features include low cardiac output; decreased stroke volume, diastolic function, and increased systemic vascular resistance. The resulting hemodynamic changes are opposite but less marked than with thyrotoxicosis. Characteristic features include low cardiac output; decreased stroke volume, diastolic function, and increased systemic vascular resistance.

22 As in patients with thyrotoxicosis, overt heart failure in hypothyroidism generally represents exacerbation of intrinsic cardiac disease. Rarely, however, hypothyroidism alone may cause cardiomyopathy. Therefore, unexplained heart failure should prompt determination of thyroid hormones. As in patients with thyrotoxicosis, overt heart failure in hypothyroidism generally represents exacerbation of intrinsic cardiac disease. Rarely, however, hypothyroidism alone may cause cardiomyopathy. Therefore, unexplained heart failure should prompt determination of thyroid hormones. In the absence of underlying heart disease, the decreased myocardial contractility observed in hypothyroidism is generally reversible after hormone replacement, probably as a result of improved calcium handling in cardiac myocytes and decreased systemic vascular resistance. In the absence of underlying heart disease, the decreased myocardial contractility observed in hypothyroidism is generally reversible after hormone replacement, probably as a result of improved calcium handling in cardiac myocytes and decreased systemic vascular resistance.

23 Total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, lipoprotein(a), and apolipoprotein B concentrations are often elevated in hypothyroidism; some patients have high serum triglyceride levels. Total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, lipoprotein(a), and apolipoprotein B concentrations are often elevated in hypothyroidism; some patients have high serum triglyceride levels. It has been demonstrated that patients with hypothyroidism have an intrinsic LDL catabolism dysfunction, which is reversible after hormone replacement. Therefore, screening for this condition is mandatory when assessing patients with hyperlipidemia. It has been demonstrated that patients with hypothyroidism have an intrinsic LDL catabolism dysfunction, which is reversible after hormone replacement. Therefore, screening for this condition is mandatory when assessing patients with hyperlipidemia. The powerful interaction between thyroid hormones and lipid metabolism is highlighted by the fact that thyroid hormones have been used in the past as lipid-lowering agents. However, this strategy was associated with increased morbidity and mortality in patients after myocardial infarction. The powerful interaction between thyroid hormones and lipid metabolism is highlighted by the fact that thyroid hormones have been used in the past as lipid-lowering agents. However, this strategy was associated with increased morbidity and mortality in patients after myocardial infarction.

24 Patients with hypothyroidism frequently have risk factors for coronary artery disease, but data to support the direct association between hypothyroidism and coronary artery disease are lacking. Patients with hypothyroidism frequently have risk factors for coronary artery disease, but data to support the direct association between hypothyroidism and coronary artery disease are lacking. The suggestion that hypothyroidism may indeed represent an independent risk factor for coronary disease comes from a population-based cross-sectional study. The suggestion that hypothyroidism may indeed represent an independent risk factor for coronary disease comes from a population-based cross-sectional study.

25 Hypothyroidism is associated with increased prevalence of hypertension. In a review of 12 studies, the overall prevalence of hypertension was 21%. In large series of hypertensive patients, hypothyroidism accounted for 3% to 5% of the cases. Hypothyroidism is associated with increased prevalence of hypertension. In a review of 12 studies, the overall prevalence of hypertension was 21%. In large series of hypertensive patients, hypothyroidism accounted for 3% to 5% of the cases. Hypothyroid patients have a low-renin form of hypertension, and the mechanism remains unknown. The causal link between thyroid hormone deficiency and hypertension is confirmed by the fact that hormone replacement may lead to improvement of hypertension. Hypothyroid patients have a low-renin form of hypertension, and the mechanism remains unknown. The causal link between thyroid hormone deficiency and hypertension is confirmed by the fact that hormone replacement may lead to improvement of hypertension.

26 Diagnosis and Therapy An elevated TSH combined with a low free T4 is diagnostic of primary hypothyroidism. Antimicrosomal and antithyroglobulin antibodies are characteristic of Hashimoto’s disease. An elevated TSH combined with a low free T4 is diagnostic of primary hypothyroidism. Antimicrosomal and antithyroglobulin antibodies are characteristic of Hashimoto’s disease. Hypothyroidism is preferentially treated with thyroxine because of its long half-life Hypothyroidism is preferentially treated with thyroxine because of its long half-life

27 Amiodarone and Thyroid Dysfunction Amiodarone is an iodine-rich benzofuran derivative with similar molecular structure to thyroid hormones. Organic iodine represents almost 40% of the molecular weight of amiodarone. A daily dose of 200 mg of amiodarone corresponds to an intake of 75 mg of organic iodide and generates approximately 7 mg of free iodine. Amiodarone is an iodine-rich benzofuran derivative with similar molecular structure to thyroid hormones. Organic iodine represents almost 40% of the molecular weight of amiodarone. A daily dose of 200 mg of amiodarone corresponds to an intake of 75 mg of organic iodide and generates approximately 7 mg of free iodine. Given the fact that the normal dietary requirement of iodine is 100 to 200 µg per day, amiodarone therapy is associated with an enormous iodide load, reflected in a 40- fold increase in plasma and urinary iodide levels. Given the fact that the normal dietary requirement of iodine is 100 to 200 µg per day, amiodarone therapy is associated with an enormous iodide load, reflected in a 40- fold increase in plasma and urinary iodide levels. it is not surprising that over 50% of the patients on amiodarone have abnormal thyroid function test results, it is not surprising that over 50% of the patients on amiodarone have abnormal thyroid function test results,

28 The predominant peripheral action of amiodarone on thyroid hormones is the inhibition of the deiodination of T4 to T3. As a result, the serum levels of T4 increase and the levels of T3 decrease The predominant peripheral action of amiodarone on thyroid hormones is the inhibition of the deiodination of T4 to T3. As a result, the serum levels of T4 increase and the levels of T3 decrease In addition, high iodide availability initially inhibits thyroid hormone synthesis. In addition, high iodide availability initially inhibits thyroid hormone synthesis. During the first 3 months of therapy, TSH levels are commonly slightly elevated because of lack of feedback inhibition, due to the lowered T3 levels, but they tend to normalize during long-term administration. During the first 3 months of therapy, TSH levels are commonly slightly elevated because of lack of feedback inhibition, due to the lowered T3 levels, but they tend to normalize during long-term administration.

29 Amiodarone-induced thyrotoxicosis (AIT) prevails in areas with low iodine intake, and hypothyroidism is more frequent in areas with high iodine intake. Amiodarone-induced thyrotoxicosis (AIT) prevails in areas with low iodine intake, and hypothyroidism is more frequent in areas with high iodine intake. Whereas thyrotoxicosis can occur throughout the treatment period and even several months after treatment, hypothyroidism rarely develops beyond 18 months of initiation of therapy. Whereas thyrotoxicosis can occur throughout the treatment period and even several months after treatment, hypothyroidism rarely develops beyond 18 months of initiation of therapy. Monitoring of thyroid function in this setting relies on TSH. If TSH is abnormal, free T4 and free T3 levels should be assessed. Additional assessments are recommended at approximately 3 months and yearly thereafter. Monitoring of thyroid function in this setting relies on TSH. If TSH is abnormal, free T4 and free T3 levels should be assessed. Additional assessments are recommended at approximately 3 months and yearly thereafter.

30 A noniodinated analog of amiodarone, dronedarone, has been synthesized. Preliminary animal data show that this compound has similar electrophysiologic effects to amiodarone. A noniodinated analog of amiodarone, dronedarone, has been synthesized. Preliminary animal data show that this compound has similar electrophysiologic effects to amiodarone. The development of dronedarone or a similar compound will be followed with interest, because iodine deletion is expected to overcome endocrine side effects of amiodarone. However, extensive safety and efficacy data in animals are required before human testing. The development of dronedarone or a similar compound will be followed with interest, because iodine deletion is expected to overcome endocrine side effects of amiodarone. However, extensive safety and efficacy data in animals are required before human testing.

31 Amiodarone-Induced Hypothyroidism incidence ranging from 13% in iodine-replete countries to 6% in countries with low or intermediate iodine intake incidence ranging from 13% in iodine-replete countries to 6% in countries with low or intermediate iodine intake TSH levels above 10 to 15 mU per L in patients on chronic amiodarone usually represent hypothyroidism. The diagnosis is confirmed by low T4 or free T4. The assessment of T3 or free T3 adds little information TSH levels above 10 to 15 mU per L in patients on chronic amiodarone usually represent hypothyroidism. The diagnosis is confirmed by low T4 or free T4. The assessment of T3 or free T3 adds little information Once the diagnosis of hypothyroidism is established, the drug can be safely continued, if needed, and thyroxine replacement added in increasing doses at 4- to 6-week intervals until TSH returns within normal limits and symptoms resolve. Once the diagnosis of hypothyroidism is established, the drug can be safely continued, if needed, and thyroxine replacement added in increasing doses at 4- to 6-week intervals until TSH returns within normal limits and symptoms resolve.

32 If amiodarone is discontinued, recovery of thyroid function is influenced by the presence of thyroid antibodies. In fact, the absence of antibodies is associated with frequent recovery, mostly within a few months, whereas patients with thyroid antibodies usually do not recover normal thyroid function. If amiodarone is discontinued, recovery of thyroid function is influenced by the presence of thyroid antibodies. In fact, the absence of antibodies is associated with frequent recovery, mostly within a few months, whereas patients with thyroid antibodies usually do not recover normal thyroid function.

33 Amiodarone-Induced Thyrotoxicosis In countries with high iodine intake, AIT is less frequent than hypothyroidism, with an estimated incidence of approximately 2%. In contrast, in the presence of iodine deficiency, AIT may occur in up to 10%. In countries with high iodine intake, AIT is less frequent than hypothyroidism, with an estimated incidence of approximately 2%. In contrast, in the presence of iodine deficiency, AIT may occur in up to 10%. Antiadrenergic effects of amiodarone may partially conceal thyrotoxic symptoms. AIT should be suspected in the presence of new or recurrent atrial arrhythmias or unexplained weight loss. Antiadrenergic effects of amiodarone may partially conceal thyrotoxic symptoms. AIT should be suspected in the presence of new or recurrent atrial arrhythmias or unexplained weight loss.

34 Three pathophysiologic mechanisms associated with thyrotoxicosis in the setting of chronic amiodarone therapy First, iodine may affect thyroid autoregulatory mechanisms and may lead, particularly in patients with underlying thyroid disease, to excessive hormone synthesis. First, iodine may affect thyroid autoregulatory mechanisms and may lead, particularly in patients with underlying thyroid disease, to excessive hormone synthesis. Second, inflammatory destructive histologic changes and increased cytokines (e.g., interleukin-6) and thyroglobulin levels have been demonstrated in this setting, suggesting a direct cytotoxic effect of amiodarone. Second, inflammatory destructive histologic changes and increased cytokines (e.g., interleukin-6) and thyroglobulin levels have been demonstrated in this setting, suggesting a direct cytotoxic effect of amiodarone. Third, it has been postulated that amiodarone may trigger an autoimmune response to the thyroid gland. Third, it has been postulated that amiodarone may trigger an autoimmune response to the thyroid gland.

35 Amiodarone should be discontinued whenever possible. Amiodarone should be discontinued whenever possible. The choice of treatment can be guided by distinction of two forms of AIT. The choice of treatment can be guided by distinction of two forms of AIT. In type I AIT patients have a goiter, positive thyroid antibodies, and abnormal (i.e., measurable or even high) 24-hour radioiodine uptake. Treatment consists of a combination of thionamides, propylthiouracil, which inhibit hormone biosynthesis, and potassium perchlorate, which blocks thyroid iodide uptake. In type I AIT patients have a goiter, positive thyroid antibodies, and abnormal (i.e., measurable or even high) 24-hour radioiodine uptake. Treatment consists of a combination of thionamides, propylthiouracil, which inhibit hormone biosynthesis, and potassium perchlorate, which blocks thyroid iodide uptake.

36 type II AIT have a normal thyroid and low radioiodine uptake. The efficacy of corticosteroids, alone or in combination with thionamides, has been convincingly demonstrated in this settin. type II AIT have a normal thyroid and low radioiodine uptake. The efficacy of corticosteroids, alone or in combination with thionamides, has been convincingly demonstrated in this settin. However, because a mixed form of AIT is frequent, patients can be approached pragmatically with an initial combination of thionamides and potassium perchlorate, with corticosteroids being added after 2 weeks if no improvement occurs. In patients not responding to this therapy, lithium may be a valid alternative. However, because a mixed form of AIT is frequent, patients can be approached pragmatically with an initial combination of thionamides and potassium perchlorate, with corticosteroids being added after 2 weeks if no improvement occurs. In patients not responding to this therapy, lithium may be a valid alternative.

37 Thank you


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