Zusammenfassung
Amiodaron verändert in typischer Weise physiologische Parameter der Schilddrüsenfunktion
bei fortbestehender Euthyreose und führt auch zu krankhaften Schilddrüsenfehlfunktionen
(Hyperthyreose, Hypothyreose). Das verbesserte pathophysiologische Verständnis der
Amiodaron-induzierten Hyperthyreose hat zur Unterscheidung von 2 unterschiedlichen
Formen der Amiodaron-induzierten Hyperthyreose (Typ 1 und Typ 2) geführt. Die beiden
Formen unterscheiden sich in charakteristischer Weise in klinischen Merkmalen und
ihrer therapeutische Beeinflussbarkeit. Die Typ-1-Hyperthyreose, die iodinduziert
auf dem Boden einer vorbestehenden Schilddrüsenerkrankung, meist einer Autonomie der
Schilddrüse nach kurzem Gebrauch des Medikamentes entsteht, wird durch eine Kombination
mit 2 antithyreoidalen Medikamenten, einem Syntheseblocker (Thiamazol) und einem Iodaufnahmeblocker
(Perchlorat) behandelt. Die Typ-2-Hyperthyreose, der eine meist ohne vorausgehende
Schilddrüsenerkrankung nach langem Medikamentengebrauch ausgelöste Thyreoiditis zugrunde
liegt, wird in milden Formen rein symptomatisch und in schweren Formen mit Glukokortikoiden
behandelt. Mischtypen kommen ebenfalls vor und werden kombiniert behandelt. Das Absetzen
von Amiodaron ist differenziert zu betrachten und, wenn überhaupt, überlegt und kontrolliert
durchzuführen. Gerade bei der Typ-2-Hyperthyreose kann das Medikament häufig ohne
negativen Einfluss auf den weiteren Verlauf belassen werden. In Deutschland selten
ist die Amiodaron-induzierte Hypothyreose, die mit Levothyroxin substituiert wird,
mit einem höheren TSH-Zielwert als ansonsten üblich.
Abstract
Amiodarone affects normal thyroid function and may induce thyroid disorders (hyperthyroidism
and hypothyroidism). Our understanding of the pathophysiology of amiodarone-associated
thyroid diseases has improved since the introduction of the drug in 1970. We discern
two types of hyperthyroidism termed type-I- and type-II-hyperthyroidism. Type-I-hyperthyroidism
is caused by the iodine excess brought about by intake of the iodine rich drug in
a patient with a pre-existing thyroid disorder, most frequently a toxic adenoma of
the thyroid. The treatment of choice in type-I-hyperthyroidism is a combination of
a thionamide drug (thiamazole) and an iodine uptake blocker (perchlorate). Type-II-hyperthyroidism
is due to thyroiditis resulting in destruction of thyroid follicles and subsequent
uncontrolled release of thyroid hormones. Therapy favours a wait and see approach
in mild cases that have a good prognosis and tend to spontaneously remit and the use
of steroids in more severe cases. Mixed types may occur and be treated with a combination
of the measures described for each type. Withdrawal of amiodarone has to be planned
carefully. In type-II-hyperthyroidism amiodarone may frequently be continued without
adverse effect on the prognosis of the thyroid disease. Amiodarone-induced hypothyroidism
is rare in Germany compared to other countries (USA). Levothyroxine replacement is
recommended. Dose is individually adjusted aiming at a higher serum TSH than in other
types of hypothyroidism.
Schlüsselwörter
Amiodaron - Iodexzess - Hyperthyreose - Thyreoiditis - Übersicht
Key words
Amiodarone - iodine excess - hyperthyroidism - thyroiditis - review
Literatur
- 1
Auer J, Berent R, Eber B.
Amiodaron in the prevention and treatment of arrhythmia.
Curr Opin Investig Drugs.
2002;
3
1037-1044
- 2
Bartalena L, Martino E, Braverman L E, Aghini-Lombardi F, Brogioni S, Grasso L.
Serum interleukin-6 in amiodaron-induced thyrotoxicosis.
J Clin Endocrinol Metab.
1994;
78
423-427
- 3
Bartalena L, Brogioni S, Grasso L, Bogazzi F, Burelli A, Martino E.
Treatment of amiodaron-induced thyrotoxicosis, a difficult challenge: results of a
prospective study.
J Clin Endocrinol Metab.
1996;
81
2930-2933
- 4
Benbassat C A, Mechlis-Frish S, Cohen M, Blum I.
Amiodaron-induced thyrotoxicosis type 2: a case report and review of the literature.
Am J Med Sci.
2000;
320
288-291
- 5
Bogazzi F, Martino E, Dell'Unto E, Brogioni S, Cosci C, Aghini-Lombardi F, Ceccarelli C,
Pinchera A, Bartalena L, Braverman L E.
Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients
with amiodaron-induced thyrotoxicosis.
J Endocrinol Invest.
2003;
26
635-640
- 6
Drvota V, Sylven C, Haggblad J, Carlsson B.
Amiodaron is a dose-dependent noncompetitive and competitive inhibitor of T3 binding
to thyroid hormone receptor subtype beta-1, whereas disopyramide, lidocaine, propafenone,
metoprolol, dl-sotalol, and verapamil have no inhibitory effect.
J Cardiovasc Pharmacol.
1995;
26
222-226
- 7
Harjai K J, Licata A A.
Effects of amiodaron on thyroid function.
Ann Intern Med.
1997;
126
63-73
- 8
Heufelder A E, Wiersinga W M.
Störungen der Schilddrüsenfunktion durch Amiodaron.
Dt Ärrztebl.
1999;
96
853-860
- 9 Hoermann R. Schilddrüsenkrankheiten. 3. Aufl. Blackwell, Berlin 2001
- 10
Holt D W, Tucker G T, Jackson P R, Storey G CA.
Amiodaron pharmacokinetics.
Am Heart J.
1983;
106
843-847
- 11
Iervasi G, Clerico A, Bonini R, Manfredi C, Berti S, Ravani M, Palmieri C, Carpi A,
Chopra I J.
Acute effects of amiodaron administration on thyroid function in patients with cardiac
arrhythmia.
J Clin Endocrinol Metab.
1997;
82
275-280
- 12
Krenning E P, Docter R, Bernard B, Visser T, Hennemann G.
Decreased transport of thyroxine (T4), 3,33′,5-triiodothyronine (T3) and 3,33′,59-triiodothyronine
(rT3) into rat hepatocytes in primary culture due to a decrease of cellular ATP content
and various drugs.
FEBS Lett.
1982;
140
229-233
- 13
Lee K L, Tai Y T.
Long-term low-dose amiodaron therapy in the management of ventricular and supraventricular
tachyarrhythmias: efficacy and safety.
Clin Cardiol.
1997;
20
372-377
- 14
Leger A F, Massin J P, Laurent M F, Vincens M, Auriol M, Helai O B, Chomette G, Savoie J C.
Iodine-induced thyrotoxicosis: analysis of eighty-five consecutive cases.
Eur J Clin Invest.
1984;
14
449-450
- 15
Martino E, Safran M, Aghini-Lombardi F, Rajatanavin R, Lenziardi M, Fay M, Pacchiarotti A,
Aronin A, Macchia E, Haffajee C, Baschieri L, Pinchera A, Braverman L E.
Environmental iodine intake and thyroid dysfunction during chronic amiodaron therapy.
Ann Intern Med.
1984;
101
28-34
- 16
Martino E, Aghini-Lombardi F, Mariotti S, Lenziardi M, Baschieri L, Braverman L E.
Treatment of amiodaron associated thyrotoxicosis by simultaneous administration of
potassium perchlorate and methimazole.
J Endocrinol Invest.
1986;
9
201-207
- 17
Martino E, Aghini-Lombardi F, Bartalena L, Grasso L, Lovielli A, Velluzzi F, Pinchera A,
Braverman L E.
Enhanced susceptibility to amiodaron-induced hypothyroidism in patients with thyroid
autoimmune disease.
Arch Intern Med.
1994;
154
2722-2726
- 18
Martino E, Bartalena L, Bogazzi F, Braverman L E.
The effects of amiodaron on the thyroid.
Endocr Rev.
2001;
22
240-254
- 19
Mazonson P D, Williams M L, Cantley L K, Daldorf L G, Utiger R D, Foster J R.
Myxedema coma during long-term amiodaron therapy.
Am J Med.
1984;
77
751-754
- 20
Mubagwa K, Macianskiene R, Viappiani S, Gendviliene V, Carlsson B, Brandts B.
KB130015, a new amiodaron derivative with multiple effects on cardiac ion channels.
Cardiovasc Drug Rev.
2003;
21
216-235
- 21
Osman F, Franklyn J A, Sheppard M C, Gammage M D.
Successful treatment of amiodaron-induced thyrotoxicosis.
Circulation.
2002;
105
1275-1277
- 22
Plomp T A, van Rossum J M, Robles de Medina E O, van Lier T, Maes R AA.
Pharmacokinetics and body distribution of amiodaron in man.
Arzneimittelforschung/Drug Res.
1984;
34
513-520
- 23
Rao R H, McReady V R, Spathis G S.
Iodine kinetic studies during amiodaron treatment.
J Clin Endocrinol Metab.
1986;
62
563-567
- 24
Roti E, Braverman L E, Bianconi L, Gardini E, Minelli R.
Thyrotoxicosis followed by hypothyroidism in patients treated with amiodaron. A possible
consequence of a destructive process in the thyroid.
Arch Intern Med.
1993;
153
886-892
- 25
Saller B, Fink H, Mann K.
Kinetics of acute and chronic iodine excess.
Exp Clin Endocrinol Diabetes.
1998;
106 (Suppl 3)
34-38
- 26
Siddoway L A.
Amiodaron: guidelines for use and monitoring.
Am Fam Physician.
2003;
68
2189-2196
- 27
Trip M D, Wiersinga W M, Plomp T A.
Incidence, predictability, and pathogenesis of amiodaron-induced thyrotoxicosis and
hypothyroidism.
Am J Med.
1991;
91
507-511
- 28
Wimpfheimer C, Staubli M, Schadelin J, Studer H.
Prednisone in amiodaron-induced thyrotoxicosis.
Br Med J.
1982;
284
1835-1836
- 29
Wong R, Cheung W, Stockigt J R, Topliss D J.
Heterogeneity of amiodaron-induced thyrotoxicosis: evaluation of colour-flow Doppler
sonography in predicting therapeutic response.
Intern Med J.
2003;
33
420-426
Prof. Dr. med. Rudolf Hörmann
Klinik für Allgemeine Innere Medizin, Endokrinologie und Gastroenterologie · Klinikum
Lüdenscheid
Paulmannshöher Str. 14
58515 Lüdenscheid
Germany
Phone: +49/23 51/46-33 31
Fax: +49/23 51/46-20 82
Email: rudolf-hoermann@t-online.de