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Amiodarone inhibits thyroidal iodide transport in vitro by a cyclic adenosine 5'-monophosphate- and iodine-independent mechanism.

Journal article
Authors Sofia Tedelind
Fredrik Larsson
C Johanson
H C van Beeren
W M Wiersinga
Ernst Nyström
Mikael Nilsson
Published in Endocrinology
Volume 147
Issue 6
Pages 2936-43
ISSN 0013-7227
Publication year 2006
Published at Institute of Medicine, Department of Internal Medicine
Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Institute of Clinical Sciences
Pages 2936-43
Language en
Links dx.doi.org/10.1210/en.2005-1246
Keywords Amiodarone, analogs & derivatives, pharmacology, Animals, Anti-Arrhythmia Agents, pharmacology, Biological Transport, drug effects, Cells, Cultured, Cyclic AMP, physiology, Electrolytes, metabolism, Iodides, metabolism, Iodine, physiology, RNA, Messenger, analysis, Swine, Symporters, genetics, physiology, Thyroid Gland, cytology, drug effects, metabolism, Thyrotropin, pharmacology
Subject categories Medical and Health Sciences

Abstract

Thyroid side effects are common in patients treated for cardiac arrhythmias with amiodarone (AM). A major disturbance is inhibited thyroidal radioiodine uptake in AM-induced thyrotoxicosis, which makes 131I therapy ineffective. On the other hand, failure to escape from the Wolff-Chaikoff effect by down-regulation of the sodium/iodide symporter (NIS) is proposed to explain AM-induced hypothyroidism. However, previously no experimental studies on the possible mechanisms have been conducted. We therefore investigated the early effects of AM on thyroidal iodide transport using bicameral chamber cultures of primary pig thyrocytes that reproduce the three tissue compartments (epithelium, lumen, and extrafollicular space) of the gland. AM dose-dependently (1-50 microm) inhibited the TSH-stimulated transepithelial (basal to apical) transport of 125I- by up to 90%. The inhibitory effect was noticed already after 8 h and was further pronounced after 1-4 d, depending on the AM concentration. The intracellularly accumulated 125I- was reduced by perchlorate but not AM, and quantitative real-time RT-PCR revealed no change in the NIS expression in AM-treated cells. Blocking of cAMP degradation with 3-isobutyl-1-methylxanthine or withdrawal of AM reversed AM-induced changes in electrolyte transport but were unable to recover the suppressed 125I- transport. The iodine-free AM analog dronedarone also inhibited 125I- transport to the same extent as AM. The findings indicate that AM blocks thyroidal iodide uptake by reducing the iodide permeability of the apical plasma membrane of the thyroid epithelial cells. The effect is iodine independent and long-lasting and does not involve impaired function of NIS or the TSH receptor/cAMP signaling pathway.

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