News:Thyroid abnormalities affect more than 30% of males on amiodarone

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October 18, 2007 By Grendel Burrell [1]

Authors from the Department of Veterans Affairs report data on thyroid dysfunction in a large cohort of male patients treated with amiodarone compared with a control group from a substudy of the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T) [1] in the American Journal of Medicine [2]. The objective of the substudy was to determine the incidence of hypothyroidism, defined as thyroid-stimulating hormone (TSH) >4.5 mU/L, or hyperthyroidism, defined as TSH <0.35 mU/L, induced by amiodarone. Patients on sotalol and those on placebo were combined as the control group.

Discovered in 1961, amiodarone was not approved for use in the United States until 1985 (http://www.wikidoc.org/index.php/Amiodarone). Effective in maintaining sinus rhythm, amiodarone causes various forms of thyroid dysfunction [3]. Amiodarone may cause changes in thyroid function tests or overt thyroid dysfunction, either amiodarone-induced thyrotoxicosis or amiodarone-induced hypothyroidism, and both may develop either in apparently normal thyroid glands or in glands with preexisting, clinically silent abnormalities. [4]

In the SAFE-T trial, 665 patients with persistent atrial fibrillation (AF) were randomized to amiodarone, sotalol, or placebo after obtaining optimal anticoagulation with an INR ranging from 2-3. Any patients not in sinus rhythm after 4 weeks of therapy were electrically cardioverted. Anticoagulation was continued for at least 8 weeks after achievement of sinus rhythm. Transtelephonic monitoring was done each week to assess recurrence of AF. Regardless of rhythm status, all patients were followed for at least 1 year. Thyroid function was assessed at baseline, 3 months, 6 months, and every 6 months by examination of TSH concentrations. 53 patients were excluded due to lack of TSH values at either baseline or during the follow up.

In this study, 99% of patients were male, and the mean age overall was 67.0 +/-9.3 years. 90% of patients were white. There were no significant differences in the prevalence of diabetes, ischemic heart disease, smoking, or baseline TSH levels betweens the groups. There was no statistical difference between the amiodarone and combined placebo/sotalol group with respect to baseline levothyroxine therapy.

For analysis, an elevation in TSH was divided into two levels. Subclinical hypothyroidism was classified as TSH >4.5-10 mU/L, and overt hypothyroidism was described as TSH>10mU/L. In the amiodarone group, there was a 25.8% incidence of subclinical hypothyroidism compared to 6.6% in the control group (P <0.001). Overt hypothyroidism developed in 5.0% of patients in the amiodarone group and in only 0.3% of control group patients (P<0.001). In all predefined assessment points, patients on amiodarone had a significantly higher likelihood of developing hypothyroidism. Additionally, there was a trend toward a higher incidence of hyperthyroidism (TSH <0.35 mU/L) in the amiodarone-treated group.

Hypothyroidism tended to develop early in the study. 58% of patients who developed hypothyroidism in the amiodarone group and 50% of the patients who developed hypothyroidism in the control group did so within the first 3 months of treatment. >75% if hypothyroidism was detected by 6 months in both groups.

When subclinical hypothyroidism is included (TSH >4.5-10 mU/L), 31% of the patients on amiodarone developed hypothyroidism. Despite a lower predisposition to thyroid dysfunction in men, in this study a significant number of patients treated with amiodarone developed some degree of hypothyroidism compared to 6.9% of the control group.

By weight, amiodarone contains 37% iodine. In a standard does of 200mg there is 300 times the usual daily iodine intake. The authors state, “Amiodarone-induced hypothyroidism is more common among populations with sufficient iodine intake.” They conclude that “amiodarone-induced hypothyroidism developed in 30.8% of older men treated with amiodarone for chronic atrial fibrillation”, and in the amiodarone-treated group, TSH levels >10 mU/L developed in 5.0% and “this should warrant treatment with thyroxine”. Hyperthyroidism occurred in 5.3% of amiodarone treated patients but was subclinical and not different from the control group. The authors recommend monitoring thyroid function at baseline, 3 months, and every 6 months during therapy with amiodarone.


References:

  1. Singh BN, Singh SN, Reda DJ; et al. (2005). "Amiodarone versus sotalol for atrial fibrillation". N. Engl. J. Med. 352 (18): 1861–72. doi:10.1056/NEJMoa041705. PMID 15872201. Unknown parameter |month= ignored (help)
  2. Batcher EL, Tang XC, Singh BN, Singh SN, Reda DJ, Hershman JM (2007). "Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation". Am. J. Med. 120 (10): 880–5. doi:10.1016/j.amjmed.2007.04.022. PMID 17904459. Unknown parameter |month= ignored (help)
  3. Melmed S, Nademanee K, Reed AW, Hendrickson JA, Singh BN, Hershman JM (1981). "Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration". J. Clin. Endocrinol. Metab. 53 (5): 997–1001. PMID 7287882. Unknown parameter |month= ignored (help)
  4. Martino E, Bartalena L, Bogazzi F, Braverman LE (2001). "The effects of amiodarone on the thyroid". Endocr. Rev. 22 (2): 240–54. PMID 11294826. Unknown parameter |month= ignored (help)

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