ketendoКлиническая и экспериментальная тиреоидологияClinical and experimental thyroidology1995-54722310-3787Endocrinology Research Centre10.14341/ket12693ketendo-12693Research ArticleОбзорыReviewsПроект федеральных клинических рекомендаций по диагностике и лечению амиодарон-индуцированной дисфункции щитовидной железыDraft of the federal clinical recommendations for diagnosisi and treatment of amiodarone-induced thyroid dysfunctionhttps://orcid.org/0000-0003-0042-7680ГриневаЕлена НиколаевнаGrinevaElena N.

Гринева Елена Николаевна, доктор медицинских наук, профессор, директор  Института эндокринологии 

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grineva_e@mail.ruhttps://orcid.org/0000-0003-4013-4831ЦойУльяна АлександровнаTsoyUliana A.

Цой Ульяна Александровна, кандидат медицинских наук, ведущий научный сотрудник, руководитель НИЛ нейроэндокринологии  Института эндокринологии 

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utsoi@mail.ruhttps://orcid.org/0000-0002-1547-0123КароноваТатьяна ЛеонидовнаKaronovaTatjana L.

Каронова Татьяна Леонидовна, доктор медицинских наук, главный научный сотрудник, руководитель НИЛ клинической эндокринологии   Института эндокринологии 

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Андрейченко Татьяна Викторовна, врач-эндокринолог 2-го эндокринологического отделения 

Санкт-Петербург

Tatjana V. Andreychenko, MD

St-Petersburg

 

andreychenko.t.v@mail.ruБогдановаГалина АлександровнаBogdanovaGalina A.

Богданова Галина Александровна, врач ультразвуковой диагностики отделения функциональной диагностики 

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Малахова Татьяна Владимировна, заведующая отделением ультразвуковой диагностики 

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Tatjana V. Malakhova, MD

Moscow

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Михайлов Евгений Николаевич, доктор медицинских наук, доцент, главный научный сотрудник НИЛ нейромодуляции 

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Рыжкова Дарья Викторовна, доктор медицинских наук, профессор РАН, главный научный сотрудник научно-исследовательского отдела ядерной медицины и тераностики Института онкологии и гематологии

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walfad@mail.ruНациональный медицинский исследовательский центр имени В.А. АлмазоваРоссияAlmazov National Medical Research CentreRussian FederationНациональный медицинский исследовательский центр эндокринологииРоссияEndocrinology Research CentreRussian FederationПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov UniversityRussian FederationПервый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский университет)РоссияI.M. Sechenov First Moscow State Medical University (Sechenov University)Russian Federation2020021220201621224Copyright © Гринева Е.Н., Цой У.А., Каронова Т.Л., Андрейченко Т.В., Богданова Г.А., Ванушко В.Э., Далматова А.Б., Данилов И.Н., Иваниха Е.В., Лебедев Д.С., Малахова Т.В., Михайлов Е.Н., Рыжкова Д.В., Татарский Б.А., Трошина Е.А., Фадеев В.В., 20212021Гринева Е.Н., Цой У.А., Каронова Т.Л., Андрейченко Т.В., Богданова Г.А., Ванушко В.Э., Далматова А.Б., Данилов И.Н., Иваниха Е.В., Лебедев Д.С., Малахова Т.В., Михайлов Е.Н., Рыжкова Д.В., Татарский Б.А., Трошина Е.А., Фадеев В.В.Grineva E.N., Tsoy U.A., Karonova T.L., Andreychenko T.V., Bogdanova G.A., Vanushko V.E., Dalmatova A.B., Danilov I.N., Ivanikha E.V., Lebedev D.S., Malakhova T.V., Mikhaylov E.N., Ryzhkova D.V., Tatarskiy B.A., Troshina E.A., Fadeev V.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.cet-endojournals.ru/jour/article/view/12693

Амиодарон - антиаритмический препарат, который применяют для лечения различных наджелудочковых и желудочковых аритмий. Молекула амиодарона сходна по структуре с молекулой тироксина и содержит два атома йода. Амиодарон и его основной активный метаболит дезэтиламиодарон  оказывают прямое дозозависимое цитотоксическое действие на фолликулярные клетки ЩЖ. Это приводит к тому, что у части пациентов, получающих амиодарон, может развиваться дисфункция щитовидной железы: амиодарон-индуцированный гипотиреоз (АиГ) или амиодарон-индуцированный тиреотоксикоз (АиТ).  Диагностика, классификация и лечение амиодарон-индуцированной дисфункции щитовидной железы, представляют сложную задачу для клинициста. Настоящий проект клинических рекомендаций разработан группой специалистов, обладающих большим опытом диагностики и лечения амиодарон-индуцированной дисфункции щитовидной железы. АиГ не требует обязательной отмены амиодарона. Лечение тироксином рекомендуется всем больным с манифестным АиГ, субклинические формы АиГ не всегда требуют его назначения. Выделяют два основных типа амиодарон-индуцированного тиреотоксикоза: АиТ 1 типа (является гипертиреозом, который развивается вследствие избыточного поступления йода, при автономных узлах ЩЖ или латентной болезни Грейвса) и АиТ 2 типа (развивается вследствие деструктивного тиреоидита из-за цитотоксического эффекта амиодарона). Также выделяют смешанную форму АиТ, для которой характерно сочетание обоих механизмов. Для автономного АиТ1 характерно наличие одного или нескольких «горячих» узлов в ЩЖ. Наличие высокого уровня  антител к рецептору ТТГ или типичных клинических проявлений подтверждает диагноз диффузного токсического зоба и, следовательно, АиТ1. В качестве основного метода дифференциальной диагностики АиТ1 и АиТ2 предлагается  использовать ЦДК, где наличие «образца 0», как правило, указывает на АиТ2, наличие «образцов I-III» с большей долей вероятности свидетельствует об АиТ1. При АиТ1 показана терапия антитиреоидными препаратами, а при АиТ2  глюкокортикоидами. Их комбинация  рекомендуется при смешанном варианте АиТ. Больным АиТ с прогрессирующим ухудшением течения сердечно-сосудистой патологии, которые не отвечают на медикаментозную терапию, рекомендуется выполнение  тиреоидэктомии в максимально короткие сроки. Если нет клинического подозрения на нарушение функции ЩЖ, то оценку тиреоидных гормонов необходимо выполнять не раньше, чем через 3 месяца от начала лечения амиодароном, затем каждые 6 месяцев.

Amiodarone is an antiarrhythmic drug that is commonly used for treatment of various supraventricular and ventricular arrhythmias. Amiodarone and its main active metabolite desethylamiodarone have a direct dose-dependent cytotoxic effect on thyroid follicular cells. Consequently, some patients receiving amiodarone may develop thyroid dysfunction: amiodarone-induced hypothyroidism (AIH) or amiodarone-induced thyrotoxicosis (AIT). The diagnosis, classification, and treatment of amiodarone-induced thyroid dysfunction remain to be a challenge to all clinicians deal with this problem. This draft of clinical recommendations was developed by a group of specialists experienced in the diagnosis and treatment of amiodarone-induced thyroid dysfunction. AIH does not require amiodarone withdrawal. Thyroxine treatment is recommended for all patients with manifest AIH, subclinical forms of AIH do not always need its prescription. There are two main types of amiodarone-induced thyrotoxicosis: AIT type 1 (is a hyperthyroidism that develops due to excessive iodine intake in autonomous thyroid nodules or latent Graves ‘ disease) and AIT type 2 (develops due to destructive thyroiditis because of the cytotoxic effect of amiodarone). In addition, there is a mixed form, which has features of both types of AIT. Autonomous AIT 1 is characterized by the presence of one or more «hot» nodules in the thyroid. Elevated TSH receptor antibodies or typical clinical manifestations confirm the diagnosis of diffuse toxic goiter and, consequently, AIT1. Colour-flow Doppler sonography (CFDS) is proposed as the basic method of differential diagnosis of AIT 1 and AIT 2. CFDS «pattern 0», usually indicates AIT 2, the presence of «patterns I-III» mostly typical for AIT 1. The thyreostatics are recommended for AIT 1, oral glucocorticoids for AIT 2 and their combination for a mixed AIT. Emergency thyroidectomy should be applied to patients with deteriorating cardiovascular pathology and ineffective drug therapy. In the absence of clinical suspicion on thyroid dysfunction, thyroid hormones assessment should be done 3 months after the start of amiodarone treatment, thereafter every 6 months.

амиодаронщитовидная железаамиодарон-индуцированный гипотиреозамиодарон-индуцированный тиреотоксикоздеструктивный тиреоидиттиреоидэктомияamiodaronethyroidamiodarone-inducedhypothyroidismamiodarone-induced thyrotoxicosisdestructive thyroditisthyroidectomyReferencesVassallo P, Trohman RG. Prescribing Amiodarone. JAMA. 2007;298(11):1312. doi: https://doi.org/10.1001/jama.298.11.1312.Vassallo P, Trohman RG. Prescribing Amiodarone. JAMA. 2007;298(11):1312. doi: https://doi.org/10.1001/jama.298.11.1312.Singh BN. Amiodarone as Paradigm for Developing New Drugs for Atrial Fibrillation. J Cardiovasc Pharmacol. 2008;52(4):300-305. doi: https://doi.org/10.1097/FJC.0b013e31818914b6.Singh BN. Amiodarone as Paradigm for Developing New Drugs for Atrial Fibrillation. J Cardiovasc Pharmacol. 2008;52(4):300-305. doi: https://doi.org/10.1097/FJC.0b013e31818914b6.Чазов Е.И., Дедов И.И. 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Endocr Rev. 2001;22(2):240-254. doi: https://doi.org/10.1210/er.22.2.240.Ahmed S, Van Gelder IC, Wiesfeld ACP, Van Veldhuisen DJ, Links TP. Determinants and outcome of amiodarone-associated thyroid dysfunction. Clin Endocrinol (Oxf). 2011;75(3):388-394. doi: https://doi.org/10.1111/j.1365-2265.2011.04087.x.Ahmed S, Van Gelder IC, Wiesfeld ACP, Van Veldhuisen DJ, Links TP. Determinants and outcome of amiodarone-associated thyroid dysfunction. Clin Endocrinol (Oxf). 2011;75(3):388-394. doi: https://doi.org/10.1111/j.1365-2265.2011.04087.x.Beddows SA, Page SR, Taylor AH, et al. Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes. Biochem Pharmacol. 1989;38(24):4397-4403. doi: https://doi.org/10.1016/0006-2952(89)90648-5.Beddows SA, Page SR, Taylor AH, et al. Cytotoxic effects of amiodarone and desethylamiodarone on human thyrocytes. 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Association between Serum Amiodarone and N-Desethylamiodarone Concentrations and Development of Thyroid Dysfunction. Clin Drug Investig. 2018;38(1):39-48. doi: https://doi.org/10.1007/s40261-017-0582-4.Свириденко Н.Ю., Платонова Н.М., Молашенко Н.В., и др. Эндокринные аспекты применения амиодарона в клинической практике. (Алгоритм наблюдения и лечения функциональных расстройств щитовидной железы) // Российский кардиологический журнал. — 2021. — №2. — С. 63-71.Sviridenko NYu, Platonova NM, Molashenko NV et al. Endocrine aspects of amiodarone therapy in clinical practice. (Follow-up and treatment algorithm for patients with thyroid dysfunction). Russian Journal of Cardiology. 2012;(2):63-71. (In Russ.).Lambert MJ, Burger AG, Galeazzi RL, Engler D. Are Selective Increases in Serum Thyroxine (T 4 )due to Iodinated Inhibitors of T 4 Monodeiodination Indicative of Hyperthyroidism? 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The authors declare that there are no conflicts of interest present.