The Relative Toxicity of Antithyroid Drugs

Trotter, Wilfred

doi:10.1177/009127006200200603

Cited by 57 publications

(21 citation statements)

References 81 publications

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“…Treatment of thyrotoxicosis (including Graves' disease) with 600-2,000 mg potassium perchlorate (430-1,400 mg perchlorate) daily for periods of several months or longer was once common practice, particularly in Europe (7,8). According to Wolff (9), although 400 mg of potassium perchlorate divided into four or five daily doses was used initially and found effective, higher doses were introduced when 400 mg/day was discovered not to control thyrotoxicosis in all subjects.…”

mentioning

confidence: 99%

Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

Greer

Pleus²,

Greer³

2002

Environ Health Perspect

417

575

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Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15.

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mentioning

confidence: 99%

Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

Greer

Pleus²,

Greer³

2002

Environ Health Perspect

417

575

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“…Por outro lado, deve-se reduzir a entrada de iodo na glândula e depletar seu conteúdo em iodo para melhorar a eficácia terapêutica das tionamidas, o que é conseguido com o uso do perclorato de potássio -1g/dia (31,32). A limitação para o uso do perclorato de potássio é a sua toxicidade, particularmente agranulocitose (ocorrência de 0,3%) e anemia aplástica, principalmente com doses superiores a 1g/dia, quando a incidência destas complicações aumenta para 16-18%, (33). A interrupção da administração do perclorato de potás-sio deve ocorrer quando o eutireoidismo for alcançado, geralmente após 6 semanas.…”

Section: Tireotoxicose Induzida Pela Amiodaronaunclassified

A amiodarona e a tireóide

Pavan

Jesus

Maciel

2004

Arq Bras Endocrinol Metab

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RESUMOA amiodarona é uma droga rica em iodo, amplamente utilizada em cardiologia clínica para o tratamento de arritmias cardíacas. O uso crônico da amiodarona está associado a uma série de efeitos colaterais, destacando-se entre eles alterações na função tireoidiana e no metabolismo dos hormônios tireoidianos, levando a indução de hipotireoidismo ou de tireotoxicose. Diversos mecanismos, incluindo distúrbios na auto-regulação tireoidiana em resposta ao excesso de iodo, fatores imunológicos e a citotoxicidade provocada pela droga, estão envolvidos na gênese da disfunção tireoidiana induzida pela amiodarona. Cerca de 50% dos indivíduos em uso crônico de amiodarona desenvolvem alguma anormalidade na função tireoidiana, o que ressalta a necessidade da monitoração das concentrações séricas dos hormônios tireoidianos e do TSH nestes pacientes. Amiodarone is an iodine-rich drug widely used for the management of cardiac arrhythmias. During long-term amiodarone therapy drug toxicity may occur and a substantial proportion of amiodarone-treated patients develop either hypothyroidism or thyrotoxicosis. Several mechanisms are involved in amiodarone-induced thyroid dysfunction: defective thyroid auto-regulatory mechanism in presence of excessive iodine offer, immunological factors and cytotoxicity. Approximately 50% of patients taking amiodarone present abnormal thyroid function. Therefore, for adequate clinical follow up of these patients, it is critical a careful monitoring of thyroid hormones and TSH, before and during treatment. AAMIODARONA FOI INTRODUZIDA na medicina clínica em meados de 1960 como agente anti-anginoso. Posteriormente, estudos de seus efeitos eletrofisiológicos consagraram seu uso como agente antiarrítmico (1,2), sendo de ampla utilização, especialmente nas arritmias refratárias aos tratamentos ditos convencionais (3). Entretanto, o uso de amiodarona está relacionado a uma série de efeitos colaterais tais como: fotossensibilidade, microdepósitos em córneas, toxicidade pulmonar, hepatotoxicidade, neuropatia periférica, hipotireoidismo e tireotoxicose (4).O propósito do presente artigo é revisar os efeitos do uso crônico de amiodarona sobre a função tireoidiana, e sugerir uma conduta adequada no diagnóstico e tratamento das disfunções tireoidianas induzidas pela droga.

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“…Additionally, perchlorate administration displaces non-organified iodide from the thyroid, and the perchlorate discharge test has been used to diagnose iodide organification defects in humans for decades [10]. Perchlorate has been shown to have side effects ranging from rash and fever to several fatal cases of aplastic anemia [13,14], though these effects typically manifest from large bolus doses administered over weeks or months [15]. …”

Section: Introductionmentioning

confidence: 99%

Radioactive Iodide (131I−) Excretion Profiles in Response to Potassium Iodide (KI) and Ammonium Perchlorate (NH4ClO4) Prophylaxis

Harris

Dallas

Rollor

et al. 2012

IJERPH

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Radioactive iodide (131I−) protection studies have focused primarily on the thyroid gland and disturbances in the hypothalamic-pituitary-thyroid axis. The objective of the current study was to establish 131I− urinary excretion profiles for saline, and the thyroid protectants, potassium iodide (KI) and ammonium perchlorate over a 75 hour time-course. Rats were administered 131I− and 3 hours later dosed with either saline, 30 mg/kg of NH4ClO4 or 30 mg/kg of KI. Urinalysis of the first 36 hours of the time-course revealed that NH4ClO4 treated animals excreted significantly more 131I− compared with KI and saline treatments. A second study followed the same protocol, but thyroxine (T4) was administered daily over a 3 day period. During the first 6–12 hour after 131I− dosing, rats administered NH4ClO4 excreted significantly more 131I− than the other treatment groups. T4 treatment resulted in increased retention of radioiodide in the thyroid gland 75 hour after 131I− administration. We speculate that the T4 treatment related reduction in serum TSH caused a decrease synthesis and secretion of thyroid hormones resulting in greater residual radioiodide in the thyroid gland. Our findings suggest that ammonium perchlorate treatment accelerates the elimination rate of radioiodide within the first 24 to 36 hours and thus may be more effective at reducing harmful exposure to 131I− compared to KI treatment for repeated dosing situations. Repeated dosing studies are needed to compare the effectiveness of these treatments to reduce the radioactive iodide burden of the thyroid gland.

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The Relative Toxicity of Antithyroid Drugs

Cited by 57 publications

References 81 publications

Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

A amiodarona e a tireóide

Radioactive Iodide (131I−) Excretion Profiles in Response to Potassium Iodide (KI) and Ammonium Perchlorate (NH4ClO4) Prophylaxis

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