Amiodarone-induced thyropathies (AmIT, AIT) are a group of thyroid pathologies caused by prolonged use of the antiarrhythmic drug amiodarone. The course is often asymptomatic, sometimes mild and moderate signs of hyperthyroidism (irritability, feeling of heat, tachycardia, tremor) or hypothyroidism (chilliness, weakness, drowsiness, fatigue) develop. Diagnostics includes blood tests for thyroxine, triiodothyronine and thyroid-stimulating hormone, scintigraphy and ultrasound with thyroid dopplerography. With hypothyroidism, hormone replacement therapy is prescribed, with thyrotoxicosis – thyrostatics or glucocorticoids.
ICD 10
E05.8 Other forms of thyrotoxicosis
Meaning
Amiodarone belongs to antiarrhythmic drugs, is widely used in cardiological practice in the treatment of severe arrhythmias, atrial and ventricular extrasystole, WPW syndrome, arrhythmias in coronary and heart failure. Among the side effects of the drug, hyper- and hypothyroidism or amiodarone-induced thyropathies are noted. Synonymous names of disorders of this group are amiodarone-induced thyroiditis, cordarone-induced thyropathies. The prevalence of pathology among patients taking the drug is about 30%. Hyperthyroidism is more often registered in regions with iodine deficiency, where its frequency reaches 12%. The epidemiology of hypothyroidism is higher in areas with moderate iodine intake, ranging from 6 to 13%.
Causes
Amiodarone consists of 39% iodine, is a benzofuran derivative, similar in molecular structure to the hormone thyroxine. During treatment with this drug, the body receives from 7 to 21 g of iodine daily with an average physiological need of 200 mcg / day. Prolonged use of amiodarone contributes to a violation of the metabolism of thyroid hormones and thyrotropin, which is manifested by hypo- or hyperthyroidism. A characteristic feature of this drug is the ability to accumulate in the liver and adipose tissue. Its half-life from the body averages 53-55 days, so amiodarone-induced thyropathies can develop 1-2 months after the completion of the course of therapy. At risk are women from 35-40 years old, elderly and senile people, as well as people with thyroid dysfunction.
Pathogenesis
Under the influence of amiodarone, the metabolism of iodized hormones changes, and their level is regulated by the pituitary gland through TSH. The drug disrupts the conversion of thyroxine to triiodothyronine in thyrotropocytes by inhibiting the enzyme deiodinase-II. The enzyme deiodes the inner ring of thyroxine, ensures its conversion to triiodothyronine, regulates the level of the metabolically inert fraction T3, maintains the concentration of this hormone in the nervous tissue. Amiodarone reduces the sensitivity of the pituitary gland to the effects of iodine-containing hormones. For this reason, most patients at the beginning of treatment show a slight increase in thyrotropin with a normal amount of thyroxine and triiodothyronine – euthyroid hyperthyrotropinemia.
Taking into account the pathogenesis, there are three types of amiodarone-induced thyropathies. In amiodarone-induced type I thyrotoxicosis, hormonal changes are associated with excessive iodine intake. The disease often occurs against the background of a predisposition to a multi-nodular goiter and functional autonomy of the thyroid gland. Cordarone-induced type II thyropathies are more common, due to the toxic effect of the drug on thyrocytes. A specific form of thyroiditis with destructive thyrotoxicosis develops. The third variant of thyroopathy is hypothyroidism. It is diagnosed in individuals whose blood contains antibodies to thyroid peroxidase, therefore, provocation of autoimmune thyroiditis by excess iodine is assumed as a pathogenetic mechanism.
Symptoms
There are three variants of the clinical picture of thyropathies provoked by taking amiodarone. With induced hypothyroidism, there are no pronounced symptoms. Most patients do not notice any changes in their well-being. Some report the appearance of daytime drowsiness and weakness, a rapid increase in fatigue when doing the usual work, the periodic occurrence of chilliness. Objectively, there is a decrease in body temperature, arterial hypotension, slowing of the pulse, swelling, menstrual cycle disorders.
Type 1 amitis is manifested by a picture of expanded hyperthyroidism. Patients become irritable, restless, anxious, have difficulty concentrating and remembering information, look forgetful, distracted. Tremor develops, hot flashes appear in the body, sweating and thirst increase. Patients have a hard time with heat and stuffiness, lose weight, and sleep poorly at night. Type 2 AmIT often has erased symptoms, since the use of amiodarone eliminates the signs of dysfunction of the cardiovascular system characteristic of thyrotoxicosis. Often, the clinical picture is represented only by muscle weakness and a decrease in body weight.
Complications
The consequences of amiodarone therapy are usually reversible, after the withdrawal of the medication, the functionality of the thyroid gland returns to normal. Persistent complications are caused by the effect of excessive amounts of hormones T3 and T4 on the heart: the course of existing arrhythmias worsens, angina attacks become more frequent, heart failure appears and worsens. Thyrotoxicosis leads to hypersensitivity of the muscle cells of the heart to the effects of adrenaline, norepinephrine, dopamine, which increases the risk of ventricular arrhythmias. Iodine-containing hormones have a direct effect on cardiomyocytes, changing their electrophysiological properties and provoking atrial fibrillation. With a prolonged course of AmIT of the first type, the development of dilated cardiomyopathy is possible.
Diagnostics
If thyroopathy is suspected, patients taking amiodarone are referred for consultation to an endocrinologist. At the initial stage of the examination, the specialist analyzes the anamnesis, specifies the duration of taking the antiarrhythmic drug, its dosage, the presence of thyroid pathologies. Complaints of patients are absent or correspond to the picture of hypo- or hyperthyroidism. The following techniques are used to confirm the diagnosis and differentiation of different types of thyropathies:
- Thyrooscintigraphy. The study of iodine radioisotopes (thyroid scintigraphy) is prescribed to patients with thyrotoxicosis. For AIT-1, normal or enhanced drug capture is characteristic, with AIT-2, a reduced accumulation of iodine in the glandular tissue is detected.
- Echography. According to the results of thyroid ultrasound and dopplerography in type 1 thyropathies, signs of a multi-nodular goiter or autoimmune gland lesion with normal or increased blood flow are diagnosed. In patients with type 2 thyropathies, blood flow is often reduced or not determined.
- Blood test (hormones and antibodies). In hypothyroidism, T4 indicators are noticeably reduced, the AT-TPO titer is increased. AmIT 1 is diagnosed by an increased level of T3, T4, TSH with a detailed clinical picture. The peculiarity of AmIT-2 is a significant increase in the level of T4 (from 60 pmol / l), a moderate increase in free T3 in combination with mild symptoms or against the background of an asymptomatic course.
Treatment
Patient management tactics are jointly determined by a cardiologist and an endocrinologist. The etiotropic direction of therapy is the cancellation of amiodarone, but in many cases this is impossible, since discontinuation of the drug provokes ventricular arrhythmia, is associated with the risk of developing life-threatening conditions. The task of therapy is to normalize the level of hormones T4 and T3. The choice of methods depends on the form of the disease:
- Hypothyroid AmIT. Manifest hypothyroidism is corrected by hormone replacement therapy. Patients are prescribed thyroxine preparations. The duration of treatment varies depending on the compensatory capabilities of the gland, the severity of the autoimmune component, the possibility of withdrawal of amiodarone.
- AmIT I. Thyrostatics are being treated. Due to the excessive intake of iodine, large doses of medications are indicated to suppress hormone production.
- AmIT II. In destructive processes in the thyroid gland, glucocorticosteroids are used, for example, prednisone. The duration of the course is up to 3 months.
- Mixed AmIT. When two forms of thyrotoxicosis are combined, a severe course of the disease is observed, requiring simultaneous use of thyrostatics and glucocorticoids. In the course of treatment, the predominant type of thyroopathy is established, one of the drugs is canceled.
If conservative treatment of thyrotoxicosis provoked by amiodarone is ineffective, radical measures aimed at suppressing the hormonal function of the thyroid gland are necessary. Total thyroidectomy (surgical removal of the gland) is performed. Patients with severe cardiac pathologies, which are a contraindication to surgery, are prescribed radioiodine therapy, which causes the death of thyrocytes.
Prognosis and prevention
The outcome of amiodarone-induced thyropathies is favorable in most cases, especially if there is a possibility of withdrawal of antiarrhythmic medication. Hypothyroidism is successfully compensated by hormone therapy, thyrotoxicosis – thyrostatics, glucocorticoids. To prevent this condition, patients taking cordarone need to conduct a blood test once every six months to determine the level of thyroid-stimulating hormone, thyroxine, triiodothyronine. The results of laboratory tests allow the endocrinologist to assess how functional the thyroid gland is, calculate the risk of developing thyroopathy.