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

Endocrinology
S TedelindM Nilsson

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...Continue Reading

Citations

Feb 12, 2013·Archives of Toxicology·Mee SongJae-Chun Ryu
Nov 26, 2009·Nature Reviews. Endocrinology·Janna Cohen-LehmanIrwin Klein
Nov 28, 2009·Best Practice & Research. Clinical Endocrinology & Metabolism·Silvia A Eskes, Wilmar M Wiersinga
Jun 26, 2009·British Journal of Clinical Pharmacology·Carmelo Lafuente-LafuenteJean-François Bergmann
Aug 30, 2008·Clinical Endocrinology·T S HanM P J Vanderpump
Sep 21, 2006·Clinical Endocrinology·Leandro Arthur DiehlWilmar M Wiersinga
Oct 2, 2007·The American Journal of Medicine·Elizabeth L BatcherUNKNOWN SAFE-T Investigators
Nov 1, 2014·Expert Review of Endocrinology & Metabolism·Kingsley Ibhazehiebo, Noriyuki Koibuchi

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