Thyroid and heart Thyroid and heart diseasesdiseases

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

In the late 1700s, a patient with clinical In the late 1700s, a patient with clinical features of thyrotoxicosis including features of thyrotoxicosis including palpitations, irregular pulse, and dyspnea palpitations, irregular pulse, and dyspnea was described . was described .

In the early 1900s, a patient with In the early 1900s, a patient with “myxedema heart” was reported: The critical “myxedema heart” was reported: The critical findings were enlarged cardiac silhouette, findings were enlarged cardiac silhouette, low electrocardiographic voltage, and low electrocardiographic voltage, and bradycardia .bradycardia .

Thyroxine (T4), is the major secretory product of the Thyroxine (T4), is the major secretory product of the

thyroid gland. Triiodothyronine (T3), the biologically thyroid gland. Triiodothyronine (T3), the biologically active compound, is in large part derived from active compound, is in large part derived from peripheral conversion of T4 by the 5'-monodeiodinase peripheral conversion of T4 by the 5'-monodeiodinase enzyme.enzyme.

Cardiovascular manifestations are frequent in Cardiovascular manifestations are frequent in thyroid dysfunction and may be the result of 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 At the cellular level, thyroid hormones act mainly through binding to specific nuclear receptors and through binding to specific nuclear receptors and activation of gene transcription . Additionally, they activation of gene transcription . Additionally, they activate extranuclear sites as mitochondrial and activate extranuclear sites as mitochondrial and membrane-bound enzymes .membrane-bound enzymes .

HyperthyroidismHyperthyroidism

Hyperthyroidism is the clinical state resulting Hyperthyroidism is the clinical state resulting from excess production of T4 , T3 or both. from excess production of T4 , T3 or both.

The most common cause is a diffuse toxic goiter The most common cause is a diffuse toxic goiter (Graves disease). Although the etiology of this (Graves disease). Although the etiology of this condition is still unknown, the hyperproduction condition is still unknown, the hyperproduction of T4 and T3 is thought to result from circulating of T4 and T3 is thought to result from circulating IgG autoantibodies that bind to the thyrotropin IgG autoantibodies that bind to the thyrotropin receptor on the thyroid gland. receptor on the thyroid gland.

The second most common form of The second most common form of hyperthyroidism is nodular toxic goiter, a hyperthyroidism is nodular toxic goiter, a condition in which localized areas of the gland condition in which localized areas of the gland function excessively and autonomously.function excessively and autonomously.

Hyperthyroidism is a relatively common disease Hyperthyroidism is a relatively common disease that occurs four to eight times more often in that occurs four to eight times more often in women than men, with a peak incidence in the women than men, with a peak incidence in the third and fourth decades. third and fourth decades.

signs and symptoms includesigns and symptoms include fatigue, hyperactivity, insomnia, heat fatigue, hyperactivity, insomnia, heat

intolerance, palpitations, dyspnea, increased intolerance, palpitations, dyspnea, increased appetite with weight loss, nocturia, diarrhea, appetite with weight loss, nocturia, diarrhea, oligomenorrhea, muscle weakness, tremor, oligomenorrhea, muscle weakness, tremor, emotional lability, increased heart rate, systolic emotional lability, increased heart rate, systolic hypertension, hyperthermia, warm moist skin, hypertension, hyperthermia, warm moist skin, lid lag, stare, and brisk reflexes. Serum T4 levels lid lag, stare, and brisk reflexes. Serum T4 levels are increased and serum TSH is suppressed are increased and serum TSH is suppressed

CARDIOVASCULAR MANIFESTATIONS.CARDIOVASCULAR MANIFESTATIONS.

Palpitations, dyspnea, tachycardia, and Palpitations, dyspnea, tachycardia, and systolic hypertension are common findings. systolic hypertension are common findings. Diastolic hypertension can also occur.Diastolic hypertension can also occur.

Typically noted are a hyperactive Typically noted are a hyperactive precordium with precordium with

a loud first heart sound, a loud first heart sound,

an accentuated pulmonic component of the an accentuated pulmonic component of the second heart sound, and second heart sound, and

a third heart sound; .a third heart sound; .

It has been suggested that many of the It has been suggested that many of the changes in cardiac function are secondary to changes in cardiac function are secondary to the increased metabolic demands of peripheral the increased metabolic demands of peripheral tissue. tissue.

also thyroid hormone exerts a direct cardiac also thyroid hormone exerts a direct cardiac stimulant action independent of its effect on stimulant action independent of its effect on general tissue metabolism,.as, normalization of general tissue metabolism,.as, normalization of the myocardial contractile response to exercise the myocardial contractile response to exercise may not occur until several months after may not occur until several months after normalization of thyroid function .normalization of thyroid function .

Roentgenographic and electrographic Roentgenographic and electrographic changes,changes,

are nonspecific in hyperthyroidism. Thus, on are nonspecific in hyperthyroidism. Thus, on chest x-ray the left ventricle, aorta, and chest x-ray the left ventricle, aorta, and pulmonary artery are prominent, and in some pulmonary artery are prominent, and in some cases, generalized cardiac enlargement can be cases, generalized cardiac enlargement can be noted.noted.

In patients with sinus rhythm, the magnitude of In patients with sinus rhythm, the magnitude of the tachycardia in general parallels the severity the tachycardia in general parallels the severity of the disease. of the disease.

Sinus tachycardia is present in 40 percent of Sinus tachycardia is present in 40 percent of patients with hyperthyroidism and occurs most patients with hyperthyroidism and occurs most frequently in the younger age groups and often frequently in the younger age groups and often at night at night

ten to 15 percent of patients with ten to 15 percent of patients with hyperthyroidism have persistent atrial hyperthyroidism have persistent atrial fibrillation, which is often heralded by one or fibrillation, which is often heralded by one or more transient episodes of this arrhythmiamore transient episodes of this arrhythmia

Intraatrial conduction disturbances, Intraatrial conduction disturbances, manifested by prolongation or notching of the manifested by prolongation or notching of the P wave and , occur in 15 and 5 percent of P wave and , occur in 15 and 5 percent of patients with hyperthyroidism, respectively. patients with hyperthyroidism, respectively.

Occasionally, second- or third-degree heart Occasionally, second- or third-degree heart block may result. The cause of the AV block may result. The cause of the AV conduction disturbance is not clearconduction disturbance is not clear

Intraventricular conduction disturbances, most Intraventricular conduction disturbances, most commonly right bundle branch block, occur in commonly right bundle branch block, occur in about 15 percent of patients with about 15 percent of patients with hyperthyroidism without associated heart hyperthyroidism without associated heart disease of other etiologydisease of other etiology

Paroxysmal supraventricular tachycardia and Paroxysmal supraventricular tachycardia and flutter are rare in hyperthyroidism.flutter are rare in hyperthyroidism.

Finally, occult thyrotoxicosis may underlie Finally, occult thyrotoxicosis may underlie either chronic or paroxysmal isolated atrial either chronic or paroxysmal isolated atrial

fibrillationfibrillation

In most instances the development of In most instances the development of clinical manifestations of heart failure and clinical manifestations of heart failure and myocardial ischemia in patients with myocardial ischemia in patients with hyperthyroidism signifies the presence of hyperthyroidism signifies the presence of underlying cardiac or coronary vascular underlying cardiac or coronary vascular disease.disease.

Both angina pectoris and heart failure occur Both angina pectoris and heart failure occur in patients with hyperthyroidism.in patients with hyperthyroidism.

For many years it was assumed that these For many years it was assumed that these conditions were seen only in the presence of conditions were seen only in the presence of underlying cardiovascular disease. underlying cardiovascular disease.

More recently, however, lines of evidence have More recently, however, lines of evidence have suggested otherwise: suggested otherwise:

(1) Congestive heart failure has been produced in (1) Congestive heart failure has been produced in experimental animals by simply administering T4 . experimental animals by simply administering T4 .

(2) Congestive heart failure may develop in (2) Congestive heart failure may develop in children with thyrotoxicosis and no underlying children with thyrotoxicosis and no underlying cardiac disease.cardiac disease.

(3) Angina has been reported in a hyperthyroid (3) Angina has been reported in a hyperthyroid patient with normal coronary arteries, presumably patient with normal coronary arteries, presumably secondary to thyroid-induced coronary artery secondary to thyroid-induced coronary artery spasm. spasm.

(4) The abnormal left ventricular function (4) The abnormal left ventricular function observed during exercise in hyperthyroid subjects observed during exercise in hyperthyroid subjects is not reversed by beta blockade but is reversed by is not reversed by beta blockade but is reversed by treating the hyperthyroidism. treating the hyperthyroidism.

The frequency of hyperthyroidism is also The frequency of hyperthyroidism is also increased in patients with familial increased in patients with familial hypertrophic cardiomyopathy.hypertrophic cardiomyopathy.

Finally, hyperthyroidism is associated with Finally, hyperthyroidism is associated with mitral value prolapse in more than a third of mitral value prolapse in more than a third of cases.cases.

DIAGNOSIS AND TREATMENT OF DIAGNOSIS AND TREATMENT OF

HYPERTHYROIDISMHYPERTHYROIDISM The diagnosis is confirmed with a low TSH level, The diagnosis is confirmed with a low TSH level,

which reflects an elevated level of thyroid hormone which reflects an elevated level of thyroid hormone in the blood. in the blood.

In elderly patients with hyperthyroidism, In elderly patients with hyperthyroidism, cardiovascular manifestations predominate, cardiovascular manifestations predominate, specifically, atrial fibrillation and/or congestive specifically, atrial fibrillation and/or congestive heart failure, and therefore evaluation of thyroid heart failure, and therefore evaluation of thyroid function in such patients is particularly important.function in such patients is particularly important.

Definitive treatment of hyperthyroidism is surgical Definitive treatment of hyperthyroidism is surgical removal of the gland or irradiation with radioactive removal of the gland or irradiation with radioactive iodide. iodide.

In severely ill patients, particularly those with In severely ill patients, particularly those with thyroid storm, significant cardiovascular thyroid storm, significant cardiovascular symptoms, or both, neither of these therapies is symptoms, or both, neither of these therapies is appropriate .appropriate .

Thus, medical therapy is directed at reducing Thus, medical therapy is directed at reducing both the production and the biological effect of both the production and the biological effect of thyroid hormone with thyroid hormone with thionamides and beta thionamides and beta blockersblockers. .

Tachycardia, palpitations, tremor, restlessness, Tachycardia, palpitations, tremor, restlessness, muscle weakness, and heat intolerance are muscle weakness, and heat intolerance are reversed by these agents, which offer the reversed by these agents, which offer the additional benefit of inhibiting the conversion of additional benefit of inhibiting the conversion of T4 to the biologically active T3 in peripheral T4 to the biologically active T3 in peripheral tissues. tissues.

TREATMENT OF CARDIOVASCULAR TREATMENT OF CARDIOVASCULAR MANIFESTATIONS OF MANIFESTATIONS OF HYPERTHYROIDISM.HYPERTHYROIDISM.

Prompt treatment of hyperthyroidism can Prompt treatment of hyperthyroidism can significantly reduce, if not eliminate the significantly reduce, if not eliminate the associated cardiovascular symptoms.associated cardiovascular symptoms.

About half of patients with concurrent onset About half of patients with concurrent onset of hyperthyroidism and angina pectoris of hyperthyroidism and angina pectoris experience complete remission of this experience complete remission of this symptom after treatment of hyperthyroidismsymptom after treatment of hyperthyroidism

Furthermore, in 30 to 40 percent of Furthermore, in 30 to 40 percent of thyrotoxic patients with atrial fibrillation thyrotoxic patients with atrial fibrillation sustained for 1 week or longer, spontaneous sustained for 1 week or longer, spontaneous reversion to sinus rhythm occurs when they reversion to sinus rhythm occurs when they become euthyroid.become euthyroid.

Beta-blocking drugs also control the ventricular Beta-blocking drugs also control the ventricular rate in atrial fibrillation. rate in atrial fibrillation.

The most useful agents for correcting the The most useful agents for correcting the fundamental defect are thionamides such as fundamental defect are thionamides such as propylthiouracil, which inhibits thyroid propylthiouracil, which inhibits thyroid hormone synthesis.hormone synthesis.

Iodine inhibits the release of thyroid hormones Iodine inhibits the release of thyroid hormones from the thyrotoxic gland, and its beneficial from the thyrotoxic gland, and its beneficial effects occur more rapidly than those of effects occur more rapidly than those of thionamides. It is therefore useful for rapid thionamides. It is therefore useful for rapid amelioration of the hyperthyroid state in amelioration of the hyperthyroid state in patients with thyroid heart disease patients with thyroid heart disease

The nonselective agent propranolol has been The nonselective agent propranolol has been traditionally used , but selective beta1-traditionally used , but selective beta1-adrenergic antagonists such as atenolol appear adrenergic antagonists such as atenolol appear equally effective. equally effective.

If beta-blockers are contraindicated, calcium If beta-blockers are contraindicated, calcium channel blockers such as verapamil or diltiazem channel blockers such as verapamil or diltiazem can be administered as negative chronotropic can be administered as negative chronotropic agent. However, caution is warranted, as these agent. However, caution is warranted, as these agents may lead to hemodynamic instability by agents may lead to hemodynamic instability by further reducing systemic vascular resistance and further reducing systemic vascular resistance and contractility.contractility.

Hyperthyroid patients with cardiovascular disease Hyperthyroid patients with cardiovascular disease are particularly resistant to therapy. It has been are particularly resistant to therapy. It has been well documented that both heart failure and well documented that both heart failure and arrhythmias are resistant to conventional doses of arrhythmias are resistant to conventional doses of cardiac glycosides., serum levels of cardiac cardiac glycosides., serum levels of cardiac glycosides are diminished in hyperthyroidism, glycosides are diminished in hyperthyroidism, because its metabolism is increased , toxicity may because its metabolism is increased , toxicity may develop at a dose that has relatively little develop at a dose that has relatively little therapeutic effect.therapeutic effect.

HypothyroidismHypothyroidism

Hypothyroidism is the clinical syndrome Hypothyroidism is the clinical syndrome associated with decreased secretion of thyroid associated with decreased secretion of thyroid hormones. This condition reflects in over 90% hormones. This condition reflects in over 90% of cases a disease of the gland itself (primary of cases a disease of the gland itself (primary hypothyroidism). Rarely, hypothyroidism can hypothyroidism). Rarely, hypothyroidism can be caused by pituitary disease (secondary be caused by pituitary disease (secondary hypothyroidism) or hypothalamic disease hypothyroidism) or hypothalamic disease (tertiary hypothyroidism).(tertiary hypothyroidism).

The most frequent cause of hypothyroidism in The most frequent cause of hypothyroidism in adults is autoimmune thyroiditis, or adults is autoimmune thyroiditis, or Hashimoto’s disease. Accordingly, women are Hashimoto’s disease. Accordingly, women are more frequently affected. more frequently affected.

clinical manifestationsclinical manifestations , ,

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

Cardiovascular InvolvementCardiovascular Involvement Bradycardia is common, and Bradycardia is common, and pericardial effusion may occur in up to one-half of pericardial effusion may occur in up to one-half of

patients but rarely causes hemodynamic patients but rarely causes hemodynamic compromise . compromise .

Both diastolic and systolic LV performance may be Both diastolic and systolic LV performance may be decreased , presumably because of alterations in decreased , presumably because of alterations in calcium uptake and release by cardiac myocytes . calcium uptake and release by cardiac myocytes . Additionally,Additionally,

an increase in systemic vascular resistance is an increase in systemic vascular resistance is observed, possibly as the result of the lack of observed, possibly as the result of the lack of direct vasodilatory effect of thyroid hormones . direct vasodilatory effect of thyroid hormones .

The resulting hemodynamic changes are opposite The resulting hemodynamic changes are opposite but less marked than with thyrotoxicosis. but less marked than with thyrotoxicosis. Characteristic features include low cardiac output; Characteristic features include low cardiac output; decreased stroke volume, diastolic function, and decreased stroke volume, diastolic function, and increased systemic vascular resistance .increased systemic vascular resistance .

As in patients with thyrotoxicosis, overt As in patients with thyrotoxicosis, overt heart heart failurefailure in hypothyroidism generally represents in hypothyroidism generally represents exacerbation of intrinsic cardiac disease. exacerbation of intrinsic cardiac disease. Rarely, however, hypothyroidism alone may Rarely, however, hypothyroidism alone may cause cardiomyopathy . Therefore, unexplained cause cardiomyopathy . Therefore, unexplained heart failure should prompt determination of heart failure should prompt determination of thyroid hormones. thyroid hormones.

In the absence of underlying heart disease, the In the absence of underlying heart disease, the decreased myocardial contractility observed in decreased myocardial contractility observed in hypothyroidism is generally reversible after hypothyroidism is generally reversible after hormone replacement , probably as a result of hormone replacement , probably as a result of improved calcium handling in cardiac myocytes improved calcium handling in cardiac myocytes and decreased systemic vascular resistance . and decreased systemic vascular resistance .

Total cholesterol, low-density lipoprotein (LDL) Total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, lipoprotein(a), and apolipoprotein B cholesterol, lipoprotein(a), and apolipoprotein B concentrations are often elevated in concentrations are often elevated in hypothyroidism; some patients have high serum hypothyroidism; some patients have high serum triglyceride levels . triglyceride levels .

It has been demonstrated that patients with It has been demonstrated that patients with hypothyroidism have an intrinsic LDL catabolism hypothyroidism have an intrinsic LDL catabolism dysfunction, which is reversible after hormone dysfunction, which is reversible after hormone replacement . Therefore, screening for this replacement . Therefore, screening for this condition is mandatory when assessing patients condition is mandatory when assessing patients with hyperlipidemia. with hyperlipidemia.

The powerful interaction between thyroid hormones The powerful interaction between thyroid hormones and lipid metabolism is highlighted by the fact that and lipid metabolism is highlighted by the fact that thyroid hormones have been used in the past as thyroid hormones have been used in the past as lipid-lowering agents. However, this strategy was lipid-lowering agents. However, this strategy was associated with increased morbidity and mortality associated with increased morbidity and mortality in patients after myocardial infarction .in patients after myocardial infarction .

Patients with hypothyroidism frequently Patients with hypothyroidism frequently have risk factors for coronary artery disease, have risk factors for coronary artery disease, but data to support the direct association but data to support the direct association between hypothyroidism and coronary artery between hypothyroidism and coronary artery disease are lacking . disease are lacking .

The suggestion that hypothyroidism may The suggestion that hypothyroidism may indeed represent an independent risk factor indeed represent an independent risk factor for coronary disease comes from a for coronary disease comes from a population-based cross-sectional study. population-based cross-sectional study.

Hypothyroidism is associated with increased Hypothyroidism is associated with increased prevalence ofprevalence of hypertension hypertension. In a review of 12 . In a review of 12 studies, the overall prevalence of studies, the overall prevalence of hypertension was 21% . In large series of hypertension was 21% . In large series of hypertensive patients, hypothyroidism hypertensive patients, hypothyroidism accounted for 3% to 5% of the cases . accounted for 3% to 5% of the cases .

Hypothyroid patients have a low-renin form of Hypothyroid patients have a low-renin form of hypertension, and the mechanism remains hypertension, and the mechanism remains unknown . The causal link between thyroid unknown . The causal link between thyroid hormone deficiency and hypertension is hormone deficiency and hypertension is confirmed by the fact that hormone confirmed by the fact that hormone replacement may lead to improvement of replacement may lead to improvement of hypertensionhypertension . .

Diagnosis and TherapyDiagnosis and Therapy

An elevated TSH combined with a low free An elevated TSH combined with a low free T4 is diagnostic of primary hypothyroidism. T4 is diagnostic of primary hypothyroidism. Antimicrosomal and antithyroglobulin Antimicrosomal and antithyroglobulin antibodies are characteristic of Hashimoto’s antibodies are characteristic of Hashimoto’s disease. disease.

Hypothyroidism is preferentially treated Hypothyroidism is preferentially treated with thyroxine because of its long half-lifewith thyroxine because of its long half-life

Amiodarone and Thyroid DysfunctionAmiodarone and Thyroid Dysfunction

Amiodarone is an iodine-rich benzofuran derivative Amiodarone is an iodine-rich benzofuran derivative with similar molecular structure to thyroid with similar molecular structure to thyroid hormones. Organic iodine represents almost 40% of hormones. Organic iodine represents almost 40% of the molecular weight of amiodarone. A daily dose the molecular weight of amiodarone. A daily dose of 200 mg of amiodarone corresponds to an intake of 200 mg of amiodarone corresponds to an intake of 75 mg of organic iodide and generates of 75 mg of organic iodide and generates approximately 7 mg of free iodine .approximately 7 mg of free iodine .

Given the fact that the normal dietary requirement Given the fact that the normal dietary requirement of iodine is 100 to 200 µg per day, amiodarone of iodine is 100 to 200 µg per day, amiodarone therapy is associated with an enormous iodide load, therapy is associated with an enormous iodide load, reflected in a 40-fold increase in plasma and reflected in a 40-fold increase in plasma and urinary iodide levels . urinary iodide levels .

it is not surprising that over 50% of the patients it is not surprising that over 50% of the patients on amiodarone have abnormal thyroid function test on amiodarone have abnormal thyroid function test results, results,

The predominant peripheral action of The predominant peripheral action of amiodarone on thyroid hormones is the amiodarone on thyroid hormones is the inhibition of the deiodination of T4 to T3. As a inhibition of the deiodination of T4 to T3. As a result, the serum levels of T4 increase and the result, the serum levels of T4 increase and the levels of T3 decreaselevels of T3 decrease

In addition, high iodide availability initially In addition, high iodide availability initially inhibits thyroid hormone synthesis. inhibits thyroid hormone synthesis.

During the first 3 months of therapy, TSH levels During the first 3 months of therapy, TSH levels are commonly slightly elevated because of lack are commonly slightly elevated because of lack of feedback inhibition, due to the lowered T3 of feedback inhibition, due to the lowered T3 levels, but they tend to normalize during long-levels, but they tend to normalize during long-term administration.term administration.

Amiodarone-induced thyrotoxicosis (AIT) Amiodarone-induced thyrotoxicosis (AIT) prevails in areas with low iodine intake, and prevails in areas with low iodine intake, and hypothyroidism is more frequent in areas with hypothyroidism is more frequent in areas with high iodine intake.high iodine intake.

Whereas thyrotoxicosis can occur throughout Whereas thyrotoxicosis can occur throughout the treatment period and even several months the treatment period and even several months after treatment, hypothyroidism rarely develops after treatment, hypothyroidism rarely develops beyond 18 months of initiation of therapy.beyond 18 months of initiation of therapy.

Monitoring of thyroid function in this setting Monitoring of thyroid function in this setting relies on TSH. If TSH is abnormal, free T4 and relies on TSH. If TSH is abnormal, free T4 and free T3 levels should be assessed. Additional free T3 levels should be assessed. Additional assessments are recommended at assessments are recommended at approximately 3 months and yearly thereafter.approximately 3 months and yearly thereafter.

A noniodinated analog of amiodarone, A noniodinated analog of amiodarone, dronedarone, has been synthesized. Preliminary dronedarone, has been synthesized. Preliminary animal data show that this compound has animal data show that this compound has similar electrophysiologic effects to amiodarone similar electrophysiologic effects to amiodarone . .

The development of dronedarone or a similar The development of dronedarone or a similar compound will be followed with interest, compound will be followed with interest, because iodine deletion is expected to overcome because iodine deletion is expected to overcome endocrine side effects of amiodarone. However, endocrine side effects of amiodarone. However, extensive safety and efficacy data in animals are extensive safety and efficacy data in animals are required before human testing.required before human testing.

Amiodarone-Induced HypothyroidismAmiodarone-Induced Hypothyroidism

incidence ranging from 13% in iodine-replete incidence ranging from 13% in iodine-replete countries to 6% in countries with low or countries to 6% in countries with low or intermediate iodine intake intermediate iodine intake

TSH levels above 10 to 15 mU per L in patients TSH levels above 10 to 15 mU per L in patients on chronic amiodarone usually represent on chronic amiodarone usually represent hypothyroidism. The diagnosis is confirmed by hypothyroidism. The diagnosis is confirmed by low T4 or free T4. The assessment of T3 or free low T4 or free T4. The assessment of T3 or free T3 adds little informationT3 adds little information

Once the diagnosis of hypothyroidism is Once the diagnosis of hypothyroidism is established, the drug can be safely continued, if established, the drug can be safely continued, if needed, and thyroxine replacement added in needed, and thyroxine replacement added in increasing doses at 4- to 6-week intervals until increasing doses at 4- to 6-week intervals until TSH returns within normal limits and symptoms TSH returns within normal limits and symptoms resolve . resolve .

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

Amiodarone-Induced ThyrotoxicosisAmiodarone-Induced Thyrotoxicosis

In countries with high iodine intake, AIT is In countries with high iodine intake, AIT is less frequent than hypothyroidism, with an less frequent than hypothyroidism, with an estimated incidence of approximately 2%. In estimated incidence of approximately 2%. In contrast, in the presence of iodine deficiency, contrast, in the presence of iodine deficiency, AIT may occur in up to 10% .AIT may occur in up to 10% .

Antiadrenergic effects of amiodarone may Antiadrenergic effects of amiodarone may partially conceal thyrotoxic symptoms. AIT partially conceal thyrotoxic symptoms. AIT should be suspected in the presence of new should be suspected in the presence of new or recurrent atrial arrhythmias or or recurrent atrial arrhythmias or unexplained weight loss.unexplained weight loss.

Three pathophysiologic mechanisms Three pathophysiologic mechanisms associated with thyrotoxicosis in the setting of associated with thyrotoxicosis in the setting of

chronic amiodarone therapychronic amiodarone therapy

First, iodine may affect thyroid autoregulatory First, iodine may affect thyroid autoregulatory mechanisms and may lead, particularly in patients mechanisms and may lead, particularly in patients with underlying thyroid disease, to excessive with underlying thyroid disease, to excessive hormone synthesis. hormone synthesis.

Second, inflammatory destructive histologic Second, inflammatory destructive histologic changes and increased cytokines (e.g., interleukin-changes and increased cytokines (e.g., interleukin-6) and thyroglobulin levels have been demonstrated 6) and thyroglobulin levels have been demonstrated in this setting, suggesting a in this setting, suggesting a direct cytotoxic effect direct cytotoxic effect of amiodaroneof amiodarone . .

Third, it has been postulated that amiodarone may Third, it has been postulated that amiodarone may trigger an autoimmune response to the thyroid trigger an autoimmune response to the thyroid gland. gland.

Amiodarone should be discontinued whenever Amiodarone should be discontinued whenever possible. possible.

The choice of treatment can be guided by The choice of treatment can be guided by distinction of two forms of AIT. distinction of two forms of AIT.

In In type I AITtype I AIT patients have a goiter, positive patients have a goiter, positive thyroid antibodies, and abnormal (i.e., thyroid antibodies, and abnormal (i.e., measurable or even high) 24-hour radioiodine measurable or even high) 24-hour radioiodine uptake. Treatment consists of a combination of uptake. Treatment consists of a combination of thionamides, propylthiouracil , which inhibit thionamides, propylthiouracil , which inhibit hormone biosynthesis, and potassium hormone biosynthesis, and potassium perchlorate, which blocks thyroid iodide perchlorate, which blocks thyroid iodide uptake .uptake .

type II AITtype II AIT have a normal thyroid and low have a normal thyroid and low radioiodine uptake. The efficacy of radioiodine uptake. The efficacy of corticosteroids, alone or in combination with corticosteroids, alone or in combination with thionamides, has been convincingly demonstrated thionamides, has been convincingly demonstrated in this settin.in this settin.

However, because However, because a mixed form of AITa mixed form of AIT is frequent, is frequent, patients can be approached pragmatically with an patients can be approached pragmatically with an initial combination of thionamides and potassium initial combination of thionamides and potassium perchlorate, with corticosteroids being added perchlorate, with corticosteroids being added after 2 weeks if no improvement occurs . In after 2 weeks if no improvement occurs . In patients not responding to this therapy, lithium patients not responding to this therapy, lithium may be a valid alternative .may be a valid alternative .

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