Amiodarone-induced hypothyroidism

Drug-induced hypothyroidism (Table 38-3) can be satisfactorily managed with levothyroxine therapy if the offending agent cannot be stopped. In the case of amiodarone-induced hypothyroidism, levothyroxine therapy may be necessary even after discontinuance because of amiodarone s very long half-life. 

Amiodarone-induced hypothyroidism has been reviewed in the light of a case of 74-year-old woman (54). 

The clinical, biochemical, and therapeutic aspects of amiodarone-induced hypothyroidism have been reviewed in the light of 18 elderly patients (75). Free thyroxine (T4) concentrations were reduced only in those with severe hypothyroidism and free triiodothyronine (T3) concentrations were always normal. Withdrawal of amiodarone in five patients led to improvement in four and worsening in one. 

The risk of amiodarone-induced hypothyroidism may be greater in patients who have pre-existing thyroid autoimmune disease (76). There is some evidence that the risk of hypothyroidism due to amiodarone is increased in elderly patients (77), but the data are not conclusive. 

In amiodarone-induced hypothyroidism the simplest method of treatment is to continue with amiodarone and to add thyroxine as required. 

Martino E, Aghini-Lombardi F, Bartalena L, Grasso L, Loviselli A, Velluzzi F, Pinchera A, Braverman LE. Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease. Arch Intern Med 1994 154(23) 2722-6. 

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 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... 

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... 

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. 

In another study, three patients with type 1 disease, two of whom had not responded to methimazole plus perchlorate, were successfully treated with a short course of iopanoic acid 1 g/day, resulting in a marked reduction in the peripheral conversion of T4 to T3 (153). Euthyroidism was restored in 7-12 days, allowing uneventful thyroidectomy. The patients were then treated with levothyroxine for hypothyroidism and amiodarone was safely restarted. The authors suggested that iopanoic acid is the drug of choice for rapid restoration of normal thyroid function before thyroidectomy in patients with drug-resistant type 1 amiodarone-induced 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). 

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 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). 

Roti, E., Minelli, R., Gardini, E., Bianconi, L., Gavuruzzi, G., Ugolotti, G., Neri, T.M., and Braverman, L.E., Iodine induced hypothyroidism in euthyroid subjects with a previous episode of amiodarone induced thyrotoxicosis, J. Clin. Endocrinol. Metab. (In Press). 

AMIODARONE INDUCED DYSTHYROIDISM HYPOTHYROIDISM FOLLOWED BY HYPERTHYROIDISM... 

Amiodarone, an anti-arythmic drug containing 37.2 % of organic iodine, may induce hypothyroidism and hyperthyroidism. Dysthyroidism can occur during treatment, but also many months after its discontinuation in patients with underlying thyroid disorders, as well as in subjects with apparently normal glands. We report the case of a patient who developed hypothyroidism followed by hyperthyroidism, related to amiodarone therapy. 

The pathogenesis of amiodarone induced dysthyroidism is discussed defective intrathyroidal autoregulation due to the high iodine level does not seem sufficient to explain hypothyroidism and h5q)erthyroidism in the same patient. Alternative explanations could be autoimmune phenomenas and genetic predisposition. 

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. 

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