benzofurans and Hyperthyroidism

Topics: Amiodarone; Benzofurans; Chemical and Drug Induced Liver Injury; Eye Diseases; Humans; Hyperthyroidism; Lung Diseases; Peripheral Nervous System Diseases; Pigmentation Disorders; Thyroid Hormones

Amiodarone induces a decrease in serum T3 whereas T4 and rT3 increase. An increase of the thyroid iodine content (TIC) is observed in all patients at the exception of those who develop hypothyroidism under treatment. Actually, no method are available to predict an induced thyroid toxicosis (ITT) and there is no reason to perform systematically thyroid function tests except if past of the patient or clinical or morphological thyroid examinations suggest thyroid abnormality. In case of suspicion of ITT it is necessary to perform T4, T3 determinations and a TRH test. TIC measurement can be useful in order to eliminate a subacute or silent thyroiditis. Hypothyroidism is generally observed in patients with autoimmune thyroiditis. Antithyroid antibodies and TSH determinations after some months of treatment can detect subclinical hypothyroidism which is due to a high susceptibility to iodide.

Topics: Amiodarone; Animals; Benzofurans; Biotransformation; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Thyroid Diseases; Thyroid Gland; Thyroid Hormones

Amiodarone is unique among the antiarrhythmic agents. Despite its unusual pharmacokinetics and its potential toxicity, it is successful in managing both supraventricular and ventricular arrhythmias. Therefore, it is destined to become an important drug in our antiarrhythmic armamentarium.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Corneal Diseases; Electrophysiology; Heart; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Lung Diseases; Skin Diseases

Amiodarone is an effective antiarrhythmic drug which has been used successfully to treat a variety of cardiac arrhythmias. Early reports emphasized both the striking efficacy of this agent and the relative paucity of side effects necessitating discontinuing treatment with this drug. As amiodarone has been used more widely and in more diverse patient populations, reports of serious thyroid, pulmonary, cardiovascular, and other adverse reactions have appeared in the literature. In this paper, we review the serious adverse effects that have been reported to date. The incidence of these reactions varies considerably in different series, and cannot be explained solely by different doses employed or by varying methods of drug administration. The final role of amiodarone in the therapy of cardiac arrhythmias cannot be determined until the long-term toxicity has been more thoroughly investigated.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Heart; Heart Conduction System; Humans; Hyperthyroidism; Infusions, Parenteral; Lung; Thyroid Gland

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Hypothyroidism; Thyroid Gland; Thyroid Hormones

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Dose-Response Relationship, Drug; Drug Interactions; Electrocardiography; Female; Humans; Hyperthyroidism; Hypothyroidism; Kinetics; Lung Diseases; Photosensitivity Disorders; Pregnancy; Skin Pigmentation; Sleep Wake Disorders; Thyroxine; Triiodothyronine

The clinical efficacy of a low-dosage schedule of amiodarone was tested in 58 patients with severe ventricular arrhythmias refractory to other drug treatments. The initially chosen regimen of 400 mg was effective at the end of the first controlled trial period (after 4 weeks) in 73% of the patients. The responsiveness was maintained with the smaller dosage of 200 mg in 68% of this group. The response was reestablished also in the patients who became nonresponders during the low-dose regimen when they returned to the initial (400-mg) dosage. No relation was found between clinical response and blood levels of amiodarone and of its deethylated metabolite. Adverse effects more often associated with amiodarone therapy were rare. However, careful monitoring of thyroid function allowed the detection in 10% of the patients of biochemically and functionally documented, but clinically silent, cases of hypo- or hyperthyroidism.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Child; Clinical Trials as Topic; Electrocardiography; Female; Heart Ventricles; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Prospective Studies; Systole

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Iodine; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Adrenergic beta-Antagonists; Adult; Arrhythmias, Cardiac; Benzofurans; Clinical Trials as Topic; Humans; Hyperthyroidism; Middle Aged; Placebos; Propranolol; Tachycardia

The effects of the thyroid status on the cytosolic free Ca2+ concentration ([Ca2+]i) in single cardiomyocytes were studied at rest and during contraction. The mean resting [Ca2+]i increased significantly from the hypothyroid (45 +/- 4 nM) through the euthyroid (69 +/- 12 nM) to the hyperthyroid condition (80 +/- 11 nM) at extracellular Ca2+ concentrations ([Ca2+]o) up to 2.5 mM. At [Ca2+]o above 2.5 mM the differences in [Ca2+]i between the groups became less. The amplitude of the Ca2+ transients became higher in all groups with increasing [Ca2+]o (1, 2.5 and 5 mM), and was highest at all [Ca2+]o in hyperthyroid myocytes. The beta-agonist isoprenaline elevated peak [Ca2+]i during contraction and increased the rate of the decay of the Ca2+ transients to a greater extent in hypothyroid myocytes than in hyperthyroid myocytes. Depolarization with high [K+]o induced a large but transient [Ca2+]i overshoot in hypothyroid myocytes, but not in hyperthyroid myocytes, before a new elevated steady-state [Ca2+]i was reached, which was not different between the groups. When isoprenaline was added to K+ o-depolarized myocytes after a steady state was reached, a significantly larger extra increase in [Ca2+]i was measured in the hypothyroid group (28%) compared with the hyperthyroid group (8%). It is concluded that in cardiac tissue exposed to increasing amounts of thyroid hormones (1) [Ca2+]i increases at rest and during contraction in cardiomyocytes and (2) interventions which favour Ca2+ entry into the cytosol [( Ca2+]o elevation, high [K+]o, beta-agonists) tend to have less impact on Ca2+ homoeostasis.

Topics: Animals; Benzofurans; Calcium; Electric Stimulation; Fura-2; Hyperthyroidism; Hypothyroidism; Isoproterenol; Male; Myocardial Contraction; Myocardium; Potassium; Rats; Rats, Inbred Strains

The incidence of amiodarone-induced thyrotoxicosis remains unclear, partly due to the difficulties encountered in making a firm diagnosis based on thyroid hormone levels. Amiodarone is known to inhibit thyroxine (T4) metabolism, thus bringing plasma T4 concentrations up to levels that may simulate T4 toxicosis. On the other hand, the iodine overload due to the drug itself may create true hyperthyroidism. The purpose of this paper is to suggest practical means of detecting thyrotoxicosis in patients on amiodarone and to discuss the treatment of this side-effect.

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Risk; Thyroid Hormones; Time Factors

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Radioimmunoassay; Thyrotropin

We measured thyrotropin in plasma by an ultrasensitive immunoradiometric assay (TSH-IRMA, "Sucrosep," Boots-Celltech), before and after thyroliberin (TRH) stimulation, in 71 patients with suspected thyroid-function disorders. Thirty-three were taking amiodarone; none was receiving (anti)thyroid drugs. The patients were divided into four groups, according to their TSH response to TRH (as measured previously by conventional TSH-RIA) and the concentrations of thyroxin (T4) and triiodothyronine (T3) in their plasma. Observed ranges of plasma TSH-IRMA (milli-int. units/L) before and after TRH were: euthyroid (n = 20), 0.2-3.0 and 1.7-15.5; subclinically hypothyroid (n = 14), 4.3-18.5 and 20-75; hyperthyroid (n = 17), less than 0.09 and less than 0.09-0.4; and subclinically hyperthyroid (n = 20), less than 0.09-1.1 and less than 0.09-2.6. Evidently TSH-IRMA results for a single sample completely distinguish hyperthyroidism from euthyroidism. However, TSH-IRMA values may also be undetectable in subclinical hyperthyroidism. The TSH response to TRH can be predicted from basal TSH-IRMA results less than 0.09 or greater than or equal to 0.8 milli-int. unit/L, intermediate values can be associated with either a normal TSH response (euthyroidism) or a decreased TSH response (subclinical hyperthyroidism only). We advocate TSH-IRMA as the first diagnostic test of thyroid function for amiodarone-treated patients.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Immunoassay; Male; Middle Aged; Thyroid Diseases; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Tachycardia

More recently a few cases of pulmonary toxicity due to amiodarone administration and reversed following drug discontinuation and corticosteroid therapy have been reported. An unusual case of recurrence of amiodarone pulmonary toxicity is described. After receiving amiodarone 1.200 mg/week for 6 month a 54-year-old woman showed clear signs of pulmonary alveolitis with ray signs of diffuse pulmonary infiltrates. The pulmonary symptoms recurred after discontinuing corticosteroidis 17 months after amiodarone was stopped and were associated with a persistent amiodarone level in broncho alveolar lavage. Only after 20 months the complete resolution of pulmonary symptoms was achieved.

Topics: Amiodarone; Benzofurans; Eye Diseases; Female; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Photosensitivity Disorders; Pulmonary Fibrosis; Radiography; Recurrence; Risk

Forty-six patients treated with amiodarone hydrochloride for a mean period of 41 +/- 3.5 months, with an average daily dose of 240 +/- 57 mg/day, have been studied. Thyroid function was assessed clinically and by laboratory tests, which included free-triiodothyronine (free-T3), free-thyroxine (free-T4) and thyrotropin. Antimicrosomal and antithyroglobulin antibodies were also looked for. Three patients (6.5%) were found to be hyperthyroid and two (4.3%) hypothyroid. Of the 41 clinically euthyroid patients, 19 (46.3%) showed one or more abnormalities in the thyroid function tests. In this group, only free-T4 was found significantly increased (p less than 0.05) as compared to both control populations. Antimicrosomal antibodies (titre greater than or equal to 1:1600) were present in 4 of 41 (9.7%) euthyroid patients, but not in hyper- or hypothyroid patients. There were no antithyroglobulin antibodies in any patients. Free hormone measurements have proved to significantly correlate with the clinical picture. Increases in free-T3 and free-T4 are the main features of hyperthyroidism, while a reduction in free-T4 serum level was specific for hypothyroidism. There are probably several mechanisms responsible for hyperthyroidism and some genetically controlled defects in synthesis and release of thyroid hormones might be among these. The presence of antithyroid antibodies could be due to deposits of amiodarone in the thyroid gland, with a consequent release of antigen from the follicle cell, but only in those patients with genetically determined defects in immunological surveillance could an autoimmune thyroiditis, with consequent hypothyroidism, develop.

Topics: Adult; Aged; Amiodarone; Autoantibodies; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Microsomes; Middle Aged; Thyroid Hormones

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Peripheral Nervous System Diseases

Therapeutic use of the potent antiarrhythmic drug amiodarone requires early detection of impending hyperthyroidism, a potentially life-threatening adverse reaction in cardiac patients. Since amiodarone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3), serum T4 and T3 levels become unreliable parameters of thyroid function. In 44 patients treated with amiodarone for a median period of 7.3 months, up to seven TRH-TSH tests were performed. The TSH response to TRH was normal in 23 patients, partially suppressed in eight, totally suppressed in eight and overshooting in five patients. Two of the eight patients with suppressed TRH-TSH tests were clinically hyperthyroid, in four others thyrotoxicosis developed within 1 to 2 1/2 months after the first observation of a suppressed TSH response, while two patients remained euthyroid. In all patients with negative TRH-TSH tests. TSH response to TRH returned to normal between 2 and 29 months after withdrawal of amiodarone. We conclude that the TRH-TSH test, repeated at intervals, is a reliable tool for assessing thyroid function in patients on long-term treatment with amiodarone. Patients with a suppressed response under amiodarone therapy are at risk of developing thyrotoxicosis. Normalization of the TSH response indicates that this risk is over.

Topics: Adolescent; Adult; Aged; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Iodine; Male; Middle Aged; Risk; Thyroid Function Tests; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Female; Heart Failure; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone

The use of amiodarone, a drug which is prescribed increasingly as an anti-anginal and anti-arrhythmic agent, necessitates a high index of suspicion for the development of thyroid disorders, especially thyrotoxicosis. Two cases, which illustrate the diagnostic dilemma of hyperthyroxinaemia and the poor response to antithyroid medication, are described. During amiodarone therapy, the clinical features of thyrotoxicosis may be masked or atypical, and the choice of therapy is complicated by a delayed response to thioamide drugs and possible contraindication for beta-blocking agents which necessitates the use of glucocorticoid drugs in some patients.

Topics: Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Carbimazole; Coronary Disease; Humans; Hyperthyroidism; Male; Prednisone; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Topics: Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroglobulin; Thyroid Hormones

Both hyperthyroidism and hypothyroidism have been noted to occur in some patients treated with amiodarone for cardiac arrhythmias. To determine the frequency of the development of thyroidal abnormalities in patients receiving amiodarone, 45 euthyroid patients were prospectively evaluated. Serum samples were obtained for measurement of thyroxine, thyrotropin, triiodothyronine, and triiodothyronine resin uptake prior to initiation of amiodarone treatment and serially over a 12- to 27-month period during which amiodarone was administered. The patients were divided into four subgroups as follows: Group I (n = 22) had elevated thyroxine levels, Group IIA (n = 13) had normal thyroxine levels and normal thyrotropin levels, Group IIB (n = 7) had normal thyroxine levels and elevated thyrotropin levels, and Group III (n = 3) had subnormal thyroxine levels. Demographic factors (such as route of administration, cardiac diagnosis, sex of the patient, or indication for amiodarone therapy) and amiodarone levels had no significant effect on the thyroid hormone parameters. However, Group I patients were statistically older than the patients in the other groups. Linear regression analysis revealed a negative correlation for thyroxine levels and a positive correlation with thyrotropin levels with age for the whole group. The various groups were not statistically affected by duration of therapy, but a positive trend existed for increasing thyroxine levels. Although virtually all patients showed changes in their thyroid hormone levels, chemical hyperthyroidism (elevated thyroxine and triiodothyronine levels without symptoms) developed in only two patients (4 percent), and clinical hyperthyroidism (elevated thyroxine and triiodothyronine levels with symptoms) developed in no patients. Four patients (9 percent) became biochemically and clinically hypothyroid. Thus, amiodarone frequently influences thyroid hormonal parameters, but less commonly causes a change in actual thyroid function. However, hyperthyroidism and hypothyroidism do occur in a significant number of patients.

Topics: Age Factors; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Prospective Studies; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine

Topics: Adult; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Thyroxine; Triiodothyronine

In a 20-year-old patient with Marfan's syndrome and Wolff-Parkinson-White syndrome, effective amiodarone treatment had to be stopped due to serious hyperthyroidism. Diagnosis and therapy of amiodarone-induced dysthyroidism is discussed.

Topics: Adult; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Marfan Syndrome; Thyroid Function Tests; Wolff-Parkinson-White Syndrome

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged

A 54-year-old man, treated with amiodarone, developed thyrotoxicosis. When rechallenged with the same drug 6 months later, he developed hypothyroidism. The therapeutic implications of this clinical sequence are discussed.

Topics: Amiodarone; Benzofurans; Coronary Disease; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Gland

Topics: Adult; Amiodarone; Benzofurans; Humans; Hyperthyroidism; Male; Tachycardia, Paroxysmal

Amiodarone associated thyrotoxicosis (AAT) occurs in approximately 10% of patients treated with this iodine rich drug in areas of mild iodine deficiency. The thyroid radioactive iodine uptake (RAIU) is usually undetectable or very low in iodine-induced thyrotoxicosis. In the present study, 35 patients with AAT were evaluated. Twelve patients had no thyroid abnormalities by physical exam and all had 24-hr RAIU less than or equal to 4%. In contrast, nine of 11 patients with AAT and diffuse goiters and eight of 12 patients with AAT and nodular goiters had RAIU values greater than 8%. In patients with AAT and goiter it appears possible that the thyroid fails to adapt normally to the excess iodide load, resulting in an inappropriately high RAIU in the presence of excess plasma iodine.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Middle Aged; Radionuclide Imaging; Thyroid Function Tests; Thyroid Gland

Topics: Amiodarone; Benzofurans; Coronary Disease; Humans; Hyperthyroidism; Male; Middle Aged

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Iodine; Male; Middle Aged; Thyroxine; Triiodothyronine

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Propylthiouracil; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyroxine

Topics: Adult; Amiodarone; Benzofurans; Dexamethasone; Humans; Hyperthyroidism

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Thyroid Function Tests

Serum thyroxine (T4), triiodothyronine (T3), resin uptake of T3 (RT3U), thyroid stimulating hormone (TSH) and TSH response to thyrotropin releasing hormone (TRH) were measured in 92 patients treated with amiodarone for up to 4 years. Two patients developed thyrotoxicosis, while euthyroid hyperthyroxinemia occurred in 29 (32%). Hypothyroidism was diagnosed in 11 patients (12%), and a further 11 had tests consistent with a "failing thyroid." Of 39 patients with normal values of T4, 15 had abnormal responses to TRH. Of the 92 patients, 24 were tested before administration of amiodarone and then sequentially; alterations in thyroid function were frequent within the first 3 months. A scheme is proposed for early recognition of disturbed thyroid function due to amiodarone.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Longitudinal Studies; Male; Middle Aged; Thyroid Diseases; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Amiodarone, an iodine-containing drug used frequently in the treatment of cardiac arrhythmias and angina pectoris, has many effects on thyroid hormone metabolism, including decreasing the production of triiodothyronine (T3) and decreasing the clearance of thyroxine and reverse T3. These effects result in elevated serum thyroxine and reverse T3 concentrations and decreased serum T3 concentrations. In addition, iodine-induced hyperthyroidism or hypothyroidism may occur in patients chronically treated with amiodarone. This study is a retrospective analysis of the incidence of thyroid dysfunction in Lucca and Pisa, West Tuscany, Italy, and in Worcester, Massachusetts. Hyperthyroidism was a more frequent (9.6%) complication of amiodarone therapy in West Tuscany, where iodine intake is moderately low; hypothyroidism was more frequent (22%) in Worcester, where iodine intake is sufficient. In patients receiving chronic amiodarone therapy, clinically suspected hyperthyroidism is best confirmed by showing elevations in serum T3 or free T3 concentrations; hypothyroidism is best diagnosed by showing an elevated serum thyrotrophin concentration. Thyroid function should be carefully monitored in patients receiving amiodarone chronically, especially if they have goiter or Hashimoto's thyroiditis.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Goiter; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Italy; Long-Term Care; Male; Massachusetts; Middle Aged; Retrospective Studies; Thyroglobulin; Thyroid Diseases; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum determinations of total T4, total T3, reverse T3, free T3 index, free T4, free T4 index, TBG, T4/TBG ratio, TSH and cholesterol were carried out on 18 euthyroid patients with coronary heart disease. Serum samples were obtained before treatment and after 15 days, 2, 4, 6, 8, 10, 12, 14 and 16 months of treatment with amiodarone (400 mg/day). Patients were divided into two groups, according to patterns of TSH response to thyrotrophin-releasing hormone (TRH): (I) patients with normal responses (n = 12), and (II) patients with subnormal responses (n = 6). Patients of group I showed total T4, free T4 and reverse T3 increments and total T3 and free T3 index decreases, whereas patients of group II were distinguished by the absence of T3 decreases and a rise in free T4 levels that showed a significant correlation with a drop in serum cholesterol (r = -0.767; p. less than 0.001). No patient of either group showed clinical signs of thyroid dysfunction. These results show that the appearance of hormonal patterns of hyperthyroidism is unpredictable and very frequent in patients with no previous thyroid abnormalities undergoing long-term treatment with the drug.

Topics: Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Long-Term Care; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine, Reverse

Thyroid function was investigated in 41 patients on chronic treatment with amiodarone. 27% of the patients had elevated total thyroxine levels together with elevated free thyroxine levels. Thyrotropin (TSH) secretion was completely suppressed in 15% of the patients. Elevated free or total thyroxine levels were frequently observed together with normal TSH secretion, although 5 of the 6 patients with suppressed TSH had markedly elevated levels. Triiodothyronine (T3) levels were low normal or below the normal range in all patients but one. This was the only patient who apparently developed amiodarone-induced hyperthyroidism. The clinical symptoms of this patient were equivocal. Thyroid function parameters including T3 levels returned to normal only 3 months after withdrawal of the drug. The patient did not need any thyrostatic treatment. The duration of treatment with amiodarone did not influence thyroid hormone concentrations, although there was an insignificant trend of increasing total thyroxine levels after a year of treatment. There was, moreover, no significant influence of the dose (200-500 mg orally/day) of amiodarone on thyroid hormone levels. Our results show that the usual screening parameters of thyroid function, namely total and free thyroxine serum concentrations, are not reliable in patients on chronic amiodarone treatment. The incidence of amiodarone-induced hypothyroidism was 2.4%. We did not observe an amiodarone-induced hypothyroidism, although there was one patient with increased TSH levels but normal T3 and thyroxine levels.

Topics: Adolescent; Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroid Gland; Thyroid Hormones; Time Factors

In order to evaluate the effects of amiodarone on thyroid function in chronically treated patients, 43 consecutive patients, who had been taking a mean weekly dose of 1420 +/- 488 mg for more than 9 months (mean 16.5 months), were studied. In a first evaluation, three patients with hypothyroidism and two with hyperthyroidism were discovered. In the remaining 38 patients, mean T4 (131 +/- 38 nmol/L) and rT3 (0.85 +/- 0.3 nmol/L) levels were significantly higher than reference values (p less than 0.05 and p less than 0.001, respectively), and mean T3 levels (1.89 +/- 0.73 nmol/L) were significantly lower (p less than 0.001). Thirteen patients showed hyperresponsiveness to thyrotropin-releasing hormone (TRH) stimulation testing. In a second evaluation, performed 12 to 18 months later, two new cases of hypothyroidism were discovered. T3 levels showed significantly lower values (p less than 0.02) than in the first evaluation, whereas basal thyroid-stimulating hormone levels and levels 30 and 60 minutes after TRH stimulation were significantly higher than those in the first evaluation (p less than 0.001). Five new hyperresponders to TRH were found. In the present series, the progressive appearance of clinical thyroid dysfunction with an elevated total incidence (16%) is demonstrated. Moreover, a progressively high prevalence of hyperresponsiveness to TRH stimulation is shown. These findings indicate that chronic amiodarone administration may carry a high risk of thyroid dysfunction.

Topics: Adult; Aged; Amiodarone; Benzofurans; Chronic Disease; Coronary Disease; Female; Follow-Up Studies; Goiter; Heart Failure; Heart Valve Diseases; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Function Tests; Thyroid Gland

Topics: Amiodarone; Benzofurans; Europe; Humans; Hyperthyroidism

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Iodine; Spectrometry, X-Ray Emission; Thyroid Gland

22 cases of hyperthyroidism occurring during or following treatment with amiodarone are reported and compared with more than 15 cases in the literature. The specific clinical features of these cases of hyperthyroidism are presented and the problems in interpretation of the laboratory thyroid function tests are discussed. A study of the course of these cases reveals a number of prognostic factors. Finally, the authors describe the practical management of this form of hyperthyroidism.

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged; Time Factors

Topics: Adult; Aged; Ambulatory Care; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged

Topics: Aged; Amiodarone; Antithyroid Agents; Benzofurans; Humans; Hyperthyroidism; Male; Middle Aged; Thyroxine; Triiodothyronine

A 54-year-old woman, with no previously documented thyroid disease, treated with amiodarone (200 mg/day, five days a week for 33 months) for paroxysmal tachyarrhythmia complicating mitral stenosis, suddenly developed extremely severe thyrotoxicosis. After therapeutic failures with carbimazole and propylthyrouracil (PTU) associated with beta-blockers, she was transferred to intensive care for plasma exchange (PE). Two PE were performed, temporarily aggravating the cardiovascular status of the patient, with no secondary improvement. The quantity of T3 removed was very small, about 1,000 ng per exchange. On the 14th day PTU had to be discontinued (toxic thrombopenia) and only symptomatic treatment was maintained (assisted ventilation, digitalis, hyperalimentation). In the 4th month, while the patient had a high total serum iodine, hypothyroidism developed due to partial block of the organification of the iodine with high TSH and fixation; this state also lasted 4 months. Spontaneous recovery was observed after 8 months. In addition a severe peripheral neuropathy was observed during the hyperthyroid phase confirmed by electromyography, distinct from the signs of thyrotoxic myopathy. This gradually regressed over 7 months and may be attributed to amiodarone therapy. The association of these two successive types of thyroid disorder due to amiodarone is an exceptionally rare phenomenon. Severe thyrotoxicosis generally requires long-term symptomatic therapy, its natural course being towards spontaneous regression. PE are ineffective on the circulating hormonal levels and were dangerous because of the underlying cardiac disease. The development of hypothyroidism at the 4th month is explained by the persistent iodine overload, and therefore prolonged surveillance after withdrawal of therapy is advised. The neurological complication of amiodarone was quite distinct from the hyperthyroid myopathy.

Topics: Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged; Peripheral Nervous System Diseases; Plasma Exchange; Time Factors

Amiodarone, an iodinated benzofuran derivative, has electrophysiologic effects on cardiac muscle akin to those of hypothyroidism. It is possible that the drug exerts its salutary effect, at least in part, by selectively inhibiting the action of triiodothyronine (T3) on the myocardium. The drug produces complex changes in thyroid hormones, with significant elevations in thyroxine (T4) and reverse T3 (rT3), with minor decreases in T3, and with minor and transient increases in thyroid-stimulating hormone, but without effect on thyroid-binding globulin. These changes may interfere with the biochemical evaluation of thyroid function. Rarely, hypothyroidism or hyperthyroidism may develop during the course of amiodarone therapy, a complication caused by the iodine contained in the drug rather than by the direct pharmacologic actions of the compound. The incidence of altered thyroid function induced is likely to vary with populations susceptible to iodine-induced goiter. Under the action of amiodarone, serum rT3 levels increase as a function of dose and duration of therapy and therefore provide a basis for judging the magnitude of in vivo drug cumulation. It was found that therapeutic efficacy was usually predictable on the basis of the attainment of a defined range of serum values, established by a correlation of rT3 levels with therapeutic responses both during loading and maintenance phases as well as after withdrawal of treatment of steady-state drug effects. Serious adverse effects occurred nearly always in association with four- to fivefold increases of rT3 above baseline values, and disappeared when such levels fell as a result of dosage reduction or after temporary drug discontinuation. The data suggest that the determination of serum rT3 levels during amiodarone therapy provides a simple and reliable technique for monitoring the drug's antiarrhythmic efficacy and toxicity, thereby enhancing its clinical utility. The use of rT3 levels may permit the development of a safe but optimal therapeutic regimen for the control of a wide spectrum of refractory atrial and ventricular tachyarrhythmias. The use of this technique, however, presupposes the allowance that must be made for variations in the methods for the serum assay of rT3 and of the systemic conditions in which the rT3 levels fluctuate relative to severity of the illness.

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Hyperthyroidism; Hypothyroidism; Iodides; Male; Middle Aged; Thyroid Gland; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

With the increasing use of amiodarone, several unwanted effects have been recognized. We reviewed 140 patients treated with amiodarone over a 5-year period in an attempt to identify patients at risk, to assess the incidence of these effects and their possible relation to dose, and to determine their outcome. The most common effect was photosensitivity (57% of patients responding to a questionnaire), whereas asymptomatic corneal microdeposits were found in all patients undergoing ophthalmologic examination. In contrast, symptomatic eye changes (colored halos) and slate-gray skin pigmentation were rare. Of the metabolic alterations, the rise in hepatic enzymes correlated with dose and plasma drug and metabolite concentrations (r = 0.59, p less than 0.001; r = 0.62, p less than 0.001, respectively) but was not associated with clinical disease. This relation to dose was not evident in patients developing clinical thyroid abnormalities (two hypothyroidism, two hyperthyroidism), all of whom had normal thyroid function prior to therapy. Four of the five hypothyroid patients were over 70 years of age. No patients developed peripheral neuropathy, but tremor and sleeplessness were common complaints (30% and 28% of patients, respectively) that responded to a decrease in dose. One patient with an abnormal chest x-ray film prior to therapy developed pulmonary fibrosis. We suggest the restricted use of high doses of amiodarone for protracted periods. Patients at particular risk are the older age group (hypothyroidism) and those with abnormal lung function prior to therapy who may be predisposed to pulmonary alveolitis. Most of the observed unwanted effects resolve when amiodarone is decreased in dose or discontinued.

Topics: Aged; Alanine Transaminase; Amiodarone; Aspartate Aminotransferases; Benzofurans; Corneal Diseases; Dose-Response Relationship, Drug; Female; Humans; Hyperthyroidism; Hypothyroidism; Lung Diseases; Male; Middle Aged; Photosensitivity Disorders; Pigmentation Disorders; Risk; Vision Disorders

Topics: Amiodarone; Arrhythmias, Cardiac; Benzofurans; Humans; Hyperthyroidism

Topics: Adult; Amiodarone; Benzofurans; Humans; Hyperthyroidism; Male; Middle Aged

Topics: Adolescent; Adult; Aged; Amiodarone; Benzofurans; Eye; Female; Heart Rate; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Myocardial Infarction; Tachycardia, Paroxysmal

Topics: Adult; Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Function Tests; Vasodilator Agents

Topics: Aged; Amiodarone; Benzofurans; Carbimazole; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroid Hormones

The effects of Amiodarone (1000-1400 mg/week, for a period ranging from 3 to 24 months) on thyroid gland function were studied in 45 patients with heart disease, using a new method of free thyroid hormone assay. Forty-four untreated patients and 11 normal subjects were used as controls. In treated patients the prevalence of dysthyroidism was 22,2% (15,6% hypothyroidism and 6,6% hyperthyroidism); the onset of dysthyroidism ranged from 20 days to 2 years after the beginning of treatment. In control patients the prevalence of dysthyroidism was 4,4% (2,2% hypothyroidism and 2,2% hyperthyroidism). In patients with hypothyroidism (TSH greater than 7 microunits/ml) T4 levels were generally low, while T3, fT4 and fT3 levels were normal. In treated patients with hyperthyroidism (fT3 greater than 5,3 pg/ml and fT4 greater than 16 pg/ml) T4 values were high, while T3 concentrations were in the normal range. In Amiodarone-treated euthyroid patients, mean T4, fT4 and rT3 values were significantly (p less than 0,01) higher than those of control subjects; TSH levels were normal in all the groups studied. These data suggest that Amiodarone can exert both a direct effect on the thyroid gland and the peripheral metabolism of thyroid hormones. The action on the thyroid gland is suggested by the high prevalence of dysthyroidism in Amiodarone-treated patients and by the high levels of T4 and fT4 observed in patients who did not show dysthyroidism. The action on the peripheral hormonal metabolism seems to be proved by the high levels of rT3 and by the prolongation of QTc interval.

Topics: Aged; Amiodarone; Anti-Arrhythmia Agents; Benzofurans; Female; Heart Diseases; Humans; Hyperthyroidism; Hypothyroidism; Male; Middle Aged; Thyroid Function Tests; Thyroid Gland

Topics: Adult; Amiodarone; Benzofurans; Humans; Hyperthyroidism; Male; Middle Aged; Prednisone; Thyroxine; Triiodothyronine

Topics: Adult; Aged; Amiodarone; Benzofurans; Biotransformation; Female; Humans; Hyperthyroidism; Iodine; Iothalamic Acid; Kinetics; Male; Middle Aged; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine

Topics: Amiodarone; Benzofurans; Humans; Hyperthyroidism; Iodine; Male; Middle Aged

The author presents his experience with the thyroid complications of amiodarone therapy: exceptional but sometimes serious conditions. Both, hypo- and hyperthyroidism can occur, probably as a result of the iodine overload on a preexisting thyroid disorder. Amiodarone has an effect on the peripheral conversion of thyroxin which leads to misleading thyroid tests results. Its beta- and alpha-blocking actions affect the clinical features, so that overdiagnosis as well as underdiagnosis are frequent. It is suggested that past or present thyroid disorder, as well as presence of antithyroid antibodies are contraindications for amiodarone therapy.

Topics: Amiodarone; Animals; Benzofurans; Dogs; Humans; Hyperthyroidism; Hypothyroidism; Iodine; Thyroid Diseases; Thyroxine; Triiodothyronine

In an estimated 5% of patients, antiarrhythmic therapy with amiodarone (Cordarone) may have side effects involving thyroid function. These unwanted effects on the thyroid gland can be classified into three entirely different categories. In addition, amiodarone invariably interferes in a characteristic way with the peripheral metabolism of thyroid hormones at the cellular level. These effects are reviewed. 1. Amiodarone contains 39% of iodine. Since its metabolism involves deiodination to inorganic iodide, classical iodine-induced thyrotoxicosis may occur in patients with nodular goiters containing autonomous follicles. 2. An entirely different form of thyrotoxicosis, resembling Graves' disease, may be induced by amiodarone in individuals with previously normal thyroid. The pathogenesis of this phenomenon is unknown. 3. In rare patients of the thyroid gland is unable to cope with pharmacological quantities of iodide, possibly due to genetic anomaly of thyroid metabolism. In these individuals amiodarone may induce hypothyroidism. 4. In contrast to the possible side effects of amiodarone involving the thyroid gland, the drug has an obligate impact on the metabolism of thyroid hormones at the level of the peripheral cells. It inhibits the peripheral conversion of thyroxin to triiodothyronine (T3) and favours the generation of reverse T3, which has no T3 activity. This and other arguments favour the assumption that the effects on the heart observed after prolonged amiodarone treatment are in fact due to selective local hypothyroidism.

Topics: Adult; Aged; Amiodarone; Arrhythmias, Cardiac; Benzofurans; Female; Humans; Hyperthyroidism; Hypothyroidism; Male; Thyroxine; Triiodothyronine

Topics: Aged; Amiodarone; Angina Pectoris; Benzofurans; Humans; Hyperthyroidism; Hypothyroidism; Middle Aged

Hyperthyroidism is a rare side effect of amiodarone treatment. Four patients with this untoward effect are described One patient with mild hyperthyroidism before treatment with amiodarone, developed prolonged severe resistant thyrotoxicosis 6 months after initiation of this drug. A second patient with Wolf-Parkinson-White syndrome and paroxysmal atrial fibrillation was successfully stabilized with amiodarone for 18 months. However, the arrhythmia recurred and the thyroid function tests were found to be elevated. In 2 other patients only slight elevation of the thyroid function tests were found without clinical manifestations 4 months after treatment with amiodarone had been initiated.

Topics: Aged; Amiodarone; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged

Topics: Adult; Amiodarone; Benzofurans; Chemical Phenomena; Chemistry; Humans; Hyperthyroidism; Male; Thyroid Gland

Topics: Amiodarone; Benzofurans; Depression, Chemical; Humans; Hyperthyroidism; Stimulation, Chemical; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The authors report four new cases of hyperthyroidism associated with prolonged treatment with amiodarone. Massive doses of beta-blockers were required to deal with the severely disordered rhythm in one of the patients. Amiodarone, which is an effective treatment for angina, is not free from risk, even at the doses which are currently accepted. Hyperthyroidism, which may occur even in patients who have had no past history of any thyroid troupble at all, remains a most unusual complication.

Topics: Adult; Amiodarone; Angina Pectoris; Arrhythmias, Cardiac; Benzofurans; Electrocardiography; Female; Humans; Hyperthyroidism; Male; Middle Aged; Pindolol; Propranolol

Topics: Amiodarone; Benzofurans; Coronary Disease; Heart Conduction System; Humans; Hyperthyroidism

Topics: Antihypertensive Agents; Benzofurans; Edema; Humans; Hyperthyroidism; Male; Middle Aged; Thiazoles

Topics: Adult; Aged; Angina Pectoris; Benzofurans; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroid Function Tests

Topics: Adult; Benzofurans; Gout; Humans; Hyperthyroidism; Male; Middle Aged; Uricosuric Agents

Topics: Benzofurans; Female; Humans; Hyperthyroidism; Joint Diseases; Middle Aged; Neurologic Manifestations; Pain; Pyramidal Tracts; Spinal Cord Diseases; Uricosuric Agents