Amiodarone thyrotoxicosis with

Patients with beta-thalassemia major have an increased risk of primary hypothyroidism. In 23 patients with beta-thalassemia amiodarone was associated with a high risk of overt hypothyroidism (33 versus 3% in controls) (43). This occurred at up to 3 months after starting amiodarone. The risk of subclinical hypothyroidism was similar in the two groups. In one case overt hypothyroidism resolved spontaneously after withdrawal, but the other patients were given thyroxine. After 21-47 months of treatment three patients developed thyrotoxicosis, with remission after withdrawal. There were no cases of hyperthyroidism in the controls. The authors proposed that patients with beta-thalassemia may be more susceptible to iodine-induced hypothyroidism, related to an underlying defect in iodine in the thyroid, perhaps associated with an effect of iron overload. 

Amiodarone may induce thyrotoxicosis (2% to 3% of patients) or hypothyroidism. It interferes with type I 5 -deiodinase, leading to reduced conversion of T4 to T3, and iodide release from the drug may contribute to iodine excess. Amiodarone also causes a destructive thyroiditis with loss of thyroglobulin and thyroid hormones. 

Andersen ED. Long-term antiarrhythmic therapy with amiodarone high prevalence of thyrotoxicosis (11%). Eur Heart J 1981 2 199. 

Thyroid hormone-producing thyroid carcinoma is an uncommon cause of thyrotoxicosis. Precipitation of thyrotoxicosis by iodine-containing compounds in patients with thyroid carcinoma is rare, but has been attributed to amiodarone in a 77-year-old man with extensive hepatic metastases from a well-differentiated thyroid carcinoma (40). 

Two patients with cardiomyopathy and resistant dysrhythmias developed thyrotoxicosis while taking amiodarone (71). Despite medical therapy, they failed to improve. Both underwent total thyroidectomy without difficulty or complications. Most reported cases of amiodarone-induced thyrotoxicosis that have been treated surgically have been of type II, i.e. with no underlying thyroid disease. 

Lithium has been used, with several other drugs, to treat four patients with amiodarone-associated thyrotoxicosis, but the drugs were ineffective in two patients, who required thyroidectomy (610). One hopes that the authors actually used milligram amounts of lithium carbonate rather than the microgram amounts listed in the article. 

Hermida JS, Tcheng E, Jarry G, Moullart V, Arlot S, Rey JL, Delonca J, Schvartz C. Radioiodine ablation of the thyroid to prevent recurrence of amiodarone-induced thyrotoxicosis in patients with resistant tachyarrhythmias. Europace 2004 6(2) 169-74. 

Williams M, Lo Gerfo P. Thyroidectomy using local anesthesia in critically ill patients with amiodarone-induced thyrotoxicosis a review and description of the technique. Thyroid 2002 12(6) 523-5. 

That amiodarone can potentiate the action of warfarin by inhibiting its metabolism is well known (SEDA-11, 156). However, potentiation of the action of warfarin has been attributed to amiodarone-induced thyrotoxicosis (264). A metabolic interaction in this case was unlikely, because the patient had taken both drugs together for 2 years before the increase in response to warfarin, coincident with the emergence of thyrotoxicosis. 

Broussolle C, Ducottet X, Martin C, Barbier Y, Bornet H, Noel G, Orgiazzi J. Rapid effectiveness of prednisone and thionamides combined therapy in severe amiodarone iodine-induced thyrotoxicosis. Comparison of two groups of patients with apparently normal thyroid glands. J Endocrinol Invest 1989 12(1) 37 2. 

Marketou ME, Simantirakis EN, Manios EG, Vardas PE. Electrical storm due to amiodarone induced thyrotoxicosis in a young adult with dilated cardiomyopathy thyroidectomy as the treatment of choice. Pacing Clin Electrophysiol 2001 24(12) 1827-8. 

Brennan MD, van Heerden JA, Carney JA. Amiodarone-associated thyrotoxicosis (AAT) experience with surgical management. Surgery 1987 102(6) 1062-7. 

Answer E. Increased sympathetic activity is a major problem in hyperthyroidism and is best managed by use of beta blockers, which can offset cardiac stimulatory effects. Propranolol has an ancillary action in thyrotoxicosis in that it prevents conversion of T4 to T3 via its inhibition of 5 deiodinase. Amiodarone causes difficult-to-predict adverse effects on thyroid function and would not be appropriate in a patient with hyperthyroidism. Bretylium is an IV agent reserved for ventricular arrhythmias. Digoxin is not ideal because of its complex actions on the heart, which include both inhibition and stimulation. 

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. 

Typical symptoms of thyrotoxicosis are often absent in patients with AIT because amiodarone has beta-blocking effects and inhibits conversion of T4 to T3. Worsening of underlying cardiac disorder, unexplained weight loss, or muscle weakness suggest the diagnosis of AIT (Harjai and Licata, 1997 Basaria and Cooper, 2005 Ursella et al, 2005). 

The treatment of type 1 AIT is more difficult than that of other forms of iodine-induced thyrotoxicosis. Discontinuation of amiodarone therapy is usually recommended in patients with type 1 AIT, as long as other anti-arrhythmic drugs are available. However, withdrawal of amiodarone is often difficult because of underlying severe heart disease. High doses of antithyroid drugs have been used to treat type 1 AIT. Combined therapy with antithyroid drugs and potassium perchlorate is recommended in patients who fail to respond to antithyroid drugs alone after 2—3 months of treatment (Basaria and Cooper,... 

Endocrine Amiodarone-induced thyrotoxicosis has been reported in three young people a 6-year-old boy with type I amiodarone-induced thyrotoxicosis, a 17-year-old girl with type II, and a 14-year-old girl with a mixed type [41 ]. 

The management of amiodarone-induced thyrotoxicosis has been extensively reviewed [42 ]. For type 1 thyrotoxicosis, thionamides are the best treatment (possibly associated with potassium perchlorate) for type 2, glucocorticoids are the treatment of choice. However, if rapid restoration of euthyroidism is necessary, a short course of iopanoic acid followed by total thyroidectomy is an option. Radioactive iodine has a marginal role. The authors addressed some important controversies, practical problems, and unanswered questions. 

What to do if amiodarone (in the event of withdrawal) needs to be given again This is not infrequent. In type 1 thyrotoxicosis, prophylactic thyroid ablation with radioactive iodine is recommended, whereas in type 2 an expectant strategy is suggested. 

Hacihamdioglu B, Berberoglu M, Siklar Z, Sava Erdeve S, O al G, Tutar E, Atalay S. Amiodarone-induced thyrotoxicosis in children and adolescents is a possible outcome in patients with low iodine intake. J Pediatr Endocrinol Metab 2010 23(4) 363-8. 

Bogazzi F, Bartalena L, Martino E. Approach to the patient with amiodarone-induced thyrotoxicosis. J Clin Endocrinol Metab 2010 95(6) 2529-35. 

In a retrospective study of the potential for major adverse cardiovascular events in 57 patients with amiodarone-induced thyrotoxicosis compared with 224 euthyroid patients for a mean of 49 months, the patients with thyrotoxicosis had a higher rate of events (32% versus 11%), mostly driven by a higher rate of ventricular tachydysrhythmias requiring admission (7.0% versus 1.3%) overall, there was a 2.7 times increased risk [26 ]. Thyrotoxicosis (HR = 2.68) and a left ventricular ejection fraction below 45% (HR = 2.52) were independent predictors of major adverse cardiovascular events. 

Amiodarone-induced thyrotoxicosis occurred in a patient with an autonomously functioning nodular goiter [35 ]. 

Differentiating between the two types of thyrotoxicosis is difficult but important for implementation of the correct therapeutic strategy. Amiodarone should be avoided in patients with toxic nodular goiters and subtotal thyroidectomy may be the treatment of choice. 

Management Glucocorticoids are the first-line treatment in type 2 amiodarone-induced thyrotoxicosis, and thionamides play no role. In a matched retrospective cohort comparison of the ejficacy of a thionamide (methimazole) or a glucocorticoid (prednisone) for 40 days in type 2 amiodarone-induced thyrotoxicosis, in 42 patients, 23% of those who took prednisone were still thyrotoxic, compared with 86% of those who took methimazole [39 ]. When those who had taken methimazole were then given prednisone, 94% achieved euthyroidism within another 40 days. 

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... 

Withdrawal of amiodarone is more often considered unnecessary by North American thyroidologists in type 1 amiodarone-induced thyrotoxicosis (which occurs in patients with latent disease, due to the iodine contained in amiodarone) than in type 2 amiodarone-induced thyrotoxicosis (which is due to destructive thyroiditis in a previously normal gland) 21% versus 10% in Europe in type 1 34% versus 20% in type 2. In type 1 thyrotoxicosis thionamides represent the treatment of choice in North America and Europe, but as monotherapy in 65% compared with 51% European thyroidologists more often consider potassium perchlorate as a useful addition (31% versus 15%). Glucocorticoids are the selected treatment for type 2 thyrotoxicosis, either alone (62% V5. 46% in Europe) or in association with thionamides (16% versus 25%). After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 less often in North America. If amiodarone needs to be restarted, prophylactic thyroid ablation is advised by 76% in type 1 thyrotoxicosis, while a wait-and-see strategy is adopted by 61% in type 2, as in Europe. This survey shows differences in therapeutic attitudes, which reflect the frequent uncertainty of the underlying mechanism that leads to amiodarone-induced thyrotoxicosis. 

Liang Y-L, Huang S-M, Peng S-L, Hsiao S-H, Hung H-C, Ou H-Y, Wu T-J. Amiodarone-induced thyrotoxicosis in a patient with autonomously functioning nodular goiter. Ann Pharmacother 2009 43(1) 134-8. 

However, these same characteristics make lithium a useful adjunct in the treatment of hyperthyroidism with i l. A 39-year-old woman with Graves disease who may have developed thyrotoxicosis secondary to treatment with amiodarone, an iodine-rich medication [92 ]. She was administered lithium 900mg/day for 12 days to increase uptake. When this was combined with two doses of 0.9 mg of recombinant human thyroid stimulating hormone (rhTSH), there was a fivefold increase in uptake [92 ]. In a retrospective study of 204 hyperthyroid patients (n = 163 Graves disease, n = 26 toxic multinodular goiter, and n=15 solitary toxic thyroid adenoma), 103 patients received alone (median dose 558 MBq) and 101 received 1 with lithium (median... 

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