Amiodarone thyroid dysfunction

There has been a retrospective study of the frequency of amiodarone-associated thyroid dysfunction in adults with congenital heart disease (41). Of 92 patients who had taken amiodarone for at least 6 months (mean age 35, range 18-60 years), 36% developed thyroid dysfunction— 19 became hyperthyroid and 14 hypothyroid. The mean dosage was 194 (100-300) mg/day, and the median duration of therapy was 3 (0.5-15) years. Female sex (OR = 3) and unoperated or palliated cyanotic congenital heart disease (OR = 7) were significant susceptibility factors for thyroid dysfunction. The risk was also dose-related. Although the authors conceded that they may have over-estimated the... 

Newman CM, Price A, Davies DW, Gray TA, Weetman AP. Amiodarone and the thyroid a practical guide to the management of thyroid dysfunction induced by amiodarone therapy. Heart 1998 79(2) 121-7. 

Rouleau F, Baudusseau O, Dupuis JM, Victor J, GesUn P. Incidence et delai d apparition des dysthyroidies sours traitement chronique par amiodarone. [Incidence and timing of thyroid dysfunction with long-term amiodarone therapy.] Arch Mai Coeur Vaiss 2001 94(l) 39-43. 

Amiodarone-induced thyroid dysfunction associated with cumulative dose. Pharmacoepidemiol Drug Saf... 

Martino E, Safran M, Aghini-Lombardi F, Rajatanavin R, Lenziardi M, Fay M, Pacchiarotti A, Aronin N, Macchia E, Haffajee C, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med 1984 101(l) 28-34. 

Thorne SA, Barnes I, CulUnan P, Somerville J. Amiodarone-associated thyroid dysfunction risk factors in adults with congenital heart disease. Circulation 1999 100(2) 149-54. 

Mariotti S, Loviselli A, Murenu S, Sau F, Valentino L, Mandas A, Vacquer S, Martino E, Balestrieri A, Lai ME. High prevalence of thyroid dysfunction in adult patients with beta-thalassemia major submitted to amiodarone treatment. J Endocrinol Invest 1999 22(l) 55-63. 

Martino E, Bartalena L, Mariotti S, Aghini-Lombardi F, Ceccarelli C, Lippi F, Piga M, Loviselli A, Braverman L, Safran M, et al. Radioactive iodine thyroid uptake in patients with amiodarone-iodine-induced thyroid dysfunction. Acta Endocrinol (Copenh) 1988 119(2) 167-73. 

Stephens JW, Baynes C, Hurel SJ. Amiodarone and thyroid dysfunction. A case-illustrated guide to management. Br J Cardiol 2001 8 499-506. 

It is unknown whether thyroid dysfunction (hypothyroidism or hyperthyroidism) is a result of the amiodarone, the iodine contained in the amiodarone, or another mechanism. The production of amiodarone-phospholipid complexes within organs has been proposed as the mechanism for some of this drug s adverse effects. The mechanism of the pulmonary toxicity seen following chronic use is also uncertain but is the result of a hypersensitivity reaction in some. 

Amiodarone causes microcrystalline deposits in the cornea and skin, thyroid dysfunction (hyper- or hypothyroidism), paresthesias, tremor, and pulmonary fibrosis. Amiodarone rarely causes new arrhythmias, perhaps because it blocks calcium channels and beta receptors as well as sodium and potassium channels. 

Quinidine has a wide spectmm of adverse effects but causes increased—not decreased—gastrointestinal motility and often results in diarrhea. Procainamide causes lupus quinidine causes thrombocytopenia amiodarone causes thyroid dysfunction. The answer is (A). 

Procainamide causes a reversible syndrome similar to lupus erythematosus Pulmonary fibrosis and thyroid dysfunction are known adverse effects of amiodarone Torsade de pointes arrhythmias are often associated with drugs that prolong action potential duration... 

Amiodarone-induced hyperthyroidism seems to be more common in males than in females and can be found in up to 15% of treated patients, especially in iodine-deficient areas (Kennedy et al, 1989). A comparison between the incidences of thyroid dysfunction in areas with low iodine intake, such as Tuscany (Italy), with that in an iodine-replete area, such as Massachusetts (USA), showed the following distribution hyperthyroidism was more common in Tuscany, with an incidence of 9.6%, than in Massachusetts, with an incidence of 2% (Martino et al, 1984). However, amiodarone-induced hypothyroidism is a more common problem in areas with iodine-repletion 22% incidence in Massachusetts vs. 5% in Tuscany (Martino et al., 1984). Amiodarone-induced hypothyroidism is often found in... 

The decrease of TSH in amiodarone-treated patients usually occurs during the first weeks of treatment. There is no rehable test to predict thyroid dysfunction caused by amiodarone. Therefore, periodic TSH determinations are useful. A prophylactic treatment is only indicated in the case of pre-existing hyperthyroidism. 

Iodine is an essential component of thyroid hormones, and iodine deficiency can lead to severe hypothyroidism. On the other hand, excessive iodine intake also results in thyroid dysfunction in certain persons. Coindent described the first case of iodine-induced hyperthyroidism in 1821 (Fradkin and Wolff, 1983), and Hurxthal (1945) reported the first case of iodine-induced hypothyroidism. Ingestion of iodine-rich foods, such as seaweed, can cause hyperthyroidism, and the incidence of hyperthyroidism showed an increase in regions of dietary iodine deficiency after prophylactic iodization of bread or salt. Iodine-containing pharmaceuticals, such as povidone-iodine (PVP-I), radiographic contrast media and amiodarone, are a major source of excessive iodine intake (Wolff, 1969 Fradkin and Wolff, 1983 Markou et aL, 2001 Roti and degli Uberti, 2001). 

Note-. There are many iodine-containing pharmaceuticais that can cause thyroid dysfunction. The majority of patients with such drug-induced thyroid dysfunction used to be found among those treated with inorganic iodine preparations, such as potassium iodide, sodium iodide, hydrogen iodide, or Lugoi s soiution. These days, however, the major sources of iodine overioad are PVP-i, contrast media and amiodarone Source Roti and Vagenakis (1991). 

Development of iodine-induced thyroid dysfunction is influenced by a person s prior iodine intake. Cases of thyrotoxicosis being induced by contrast media are mainly reported in Europe or Australia, where dietary iodine levels are low, as described by Fradkin and Wolff (1983). Except for cases due to amiodarone, the incidence of iodine-induced hyperthyroidism is very low in regions where dietary iodine is adequate (Roti and degfl Uberti, 2001). Neonates treated with PVP-I often develop hypothyroidism in iodine-insufficient regions of Europe, but rarely do so in iodine-sufficient regions of the United States, as described by Brown et al. (1997). Thus, persons who five in areas where iodine is deficient in the diet are at risk of developing thyroid dysfunction induced by iodine-containing pharmaceuticals. 

Among the types of thyroid dysfunction induced by such pharmaceuticals, hypothyroidism in the fetus or neonate and amiodarone-induced thyrotoxicosis (AIT) are severe problems. 

Amiodarone also has intrinsic effects on the thyroid and thyroid hormone production besides those related to excessive iodine intake (Table 96.4), and this means that it induces thyroid dysfunction more frequently than any other iodine-containing pharmaceutical. 

The estimated incidence of amiodarone-induced thyroid dysfunction varies widely from 2 to 24% (Albert et ai, 1987). Amiodarone-induced hypothyroidism (AIH) is prevalent in iodine-sufficient areas, while AIT occurs... 

Amiodarone and iodine both readily cross the placenta, so amiodarone-induced thyroid dysfunction can occur in neonates when pregnant women are treated with amiodarone. Hypothyroidism was reported in 17% of the infants born to women treated with amiodarone and neu-rodevelopmental assessment of these hypothyroid infants showed mild abnormalities, which were also reported in some euthyroid infants exposed to amiodarone, suggesting that there might be a direct neurotoxic effect of this drug during fetal development (Bartalena et ai, 2001). 

Iodine-containing pharmaceuticals, such as PVP-I, radiographic contrast media and amiodarone, are a major cause of excessive iodine intake inducing thyroid dysfunction. 

Amiodarone therapy often causes thyroid dysfunction. 

Amiodarone may cause thyroid dysfunction, which may affect theophylline requirements, see also Theophylline + Thyroid and Antithyroid compounds , p.l200. 

The theophylline elimination rate constant after a single intravenous dose of aminophylline was found to be greater in hyperthyroid patients (0.155 h ) than in euthyroid (0.107 h ) or hypothyroid patients (0.060 h ) some other pharmacokinetic parameters were also changed. The authors concluded that thyroid dysfunction may modestly alter theophylline requirements. It is therefore also likely that drug-induced changes in the thyroid status, such as those caused by amiodarone, may also alter the amount of theophylline needed to maintain therapeutic levels. 

This monitoring would also apply to drugs that may cause thyroid dysfunction such as amiodarone. 

The American Thyroid Association has investigated how North American thyroid-ologists assess and treat amiodarone-induced thyrotoxicosis and has compared the results with those of a survey using the same questionnaire previously carried out among European thyroidologists [40 ]. Most of the respondents (91% versus 68% in Europe) see under 10 new cases of amiodarone-induced thyrotoxicosis per year, which seems to be less common than amiodarone-induced hypothyroidism in North America (34% and 66% of amiodarone-induced thyroid dysfunction respectively, compared with 75% and 25% in Europe). When thyrotoxicosis is suspected in North America hormonal assessment is mostly based on measurements of serum-free T4 and TSH, while serum-free T3 determination is requested less often than... 

Endocrine In patients receiving the minimum dose of amiodarone, thyroid abnormalities were observed at a rate between 14% and 18%. The effects on the thyroid gland are variable. Amiodarone may cause abnormal thyroid function detected only by laboratory test as well as clinically manifested thyroid dysfunction. The mechanism of this adverse effect is complex. Amiodarone inhibits the action of deiodinase and decreases peripheral conversion of thyroid hormones. Moreover, it decreases their renal elimination and inhibits their entry to peripheral tissues. The level of T4 increases by 40% within 1-4 months of amiodarone therapy. The deiodinase activity inhibition can be noticed after 3 months of treatment. It leads to an increase in the level of thyroid stimulating hormones. Amiodarone and its metabolite have a direct cytotoxic effect on thyroid follicular cells, which results in destructive thyroiditis. Amiodarone-induced thyroid damage can lead either to hypo- or hyperthyroidism. The latter can be of two types. Type 1 usually occurs in patients with prior thyroid damage. In this type, iodine excess causes excessive synthesis of thyroid hormones whereas in type 2 the inflammatory process is followed by destruction. A destructive thyroiditis leads to the release of hormones from damaged thyroid follicular cells. This mechanism occurs in patients with no history of thyroid disorders [15]. 

Costache II, Aprotosoaie AC. Clinical and therapeutic aspects of amiodarone induced thyroid dysfunction. Rev Med Chir Soc Med Nat Iasi... 

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