Intrathyroidal Concentrations of Methimazole in Patients with Graves’ Disease*

Jansson, R; Dahlberg, Per Anders; Johansson, Henry; Lindström, Björn

doi:10.1210/jcem-57-1-129

Cited by 110 publications

(41 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Circulating levels were about fourfold higher than the average levels reported for humans (Mortimer et al 1997), but relative differences in tissue levels might also apply to humans where tissue data are scarce. As in humans and rats (Marchant & Alexander 1972, Jansson et al 1983, MMI specifically accumulated in the thyroid gland. About sixfold lower levels were present in the liver, mainly in the reduced form.…”

Section: Discussionmentioning

confidence: 93%

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Herck

Geysens²,

Bald³

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T 4 ) content but an increase in thyroidal 3,5,3 0 -triiodothyronine (T 3 ) content. This resulted in normal T 3 levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T 4 availability was only moderately affected in embryos. Peripheral T 3 levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T 3 content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T 3 content, which is reduced throughout the embryonic development period.

show abstract

Section: Discussionmentioning

confidence: 93%

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Herck

Geysens²,

Bald³

et al. 2013

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…However, patients obtain longterm antithyroid treatment, which may last for years, and the turnover of thionamides is slow in tissue compared with a short plasma half-life (Jansson et al, 1983). This might result in drug accumulation as demonstrated for related agents (Turcant et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

Carbimazole Is an Inhibitor of Protein Synthesis and Protects from Neuronal Hypoxic Damage In Vitro

Lehane

Guelzow

Zenker

et al. 2013

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Oxygen deprivation during ischemic or hemorrhagic stroke results in ATP depletion, loss of ion homeostasis, membrane depolarization, and excitotoxicity. Pharmacologic restoration of cellular energy supply may offer a promising concept to reduce hypoxic cell injury. In this study, we investigated whether carbimazole, a thionamide used to treat hyperthyroidism, reduces neuronal cell damage in oxygen-deprived human SK-N-SH cells or primary cortical neurons. Our results revealed that carbimazole induces an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) that was associated with a marked inhibition of global protein synthesis. Translational inhibition resulted in significant bioenergetic savings, preserving intracellular ATP content in oxygen-deprived neuronal cells and diminishing hypoxic cellular damage. Phosphorylation of eEF2 was mediated by AMP-activated protein kinase and eEF2 kinase. Carbimazole also induced a moderate calcium influx and a transient cAMP increase. To test whether translational inhibition generally diminishes hypoxic cell damage when ATP availability is limiting, the translational repressors cycloheximide and anisomycin were used. Cycloheximide and anisomycin also preserved ATP content in hypoxic SK-N-SH cells and significantly reduced hypoxic neuronal cell damage. Taken together, these data support a causal relation between the pharmacologic inhibition of global protein synthesis and efficient protection of neurons from ischemic damage by preservation of high-energy metabolites in oxygen-deprived cells. Furthermore, our results indicate that carbimazole or other translational inhibitors may be interesting candidates for the development of new organprotective compounds. Their chemical structure may be used for computer-assisted drug design or screening of compounds to find new agents with the potential to diminish neuronal damage under ATP-limited conditions.

show abstract

“…There must be other explanations. Although propylthiouracil has a shorter half-life in serum than has methimazole (55), propylthiouracil and its metabolites are concentrated and retained in human thyroid more than methimazole and its metabolites (56,57). If, for example, the radioprotective effect of the thionamides is distinct from their inhibition of thyroid hormone synthesis, the therapeutic dose of propylthiouracil being 10 times greater than that of methimazole may be significant.…”

Section: Therapy?mentioning

confidence: 99%

Controversies in radioiodine therapy: relation to ophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in large goitres

Bonnema

Bartalena

Toft

et al. 2002

European Journal of Endocrinology

View full text Add to dashboard Cite

In routine use for more than 50 years, radioiodine ( 131 I) is generally considered safe and devoid of major side effects. Therefore, it is surprising that relatively many aspects of radioiodine therapy are controversial, as illustrated by recent international questionnaire studies. Our review aims at highlighting three of these areas -namely, the influence of 131 I on the course of Graves' ophthalmopathy, the possible radioprotective effects of antithyroid drugs, and the use of 131 I in large goitres. 131 I therapy carries a small (but definite) risk of causing progression of Graves' ophthalmopathy. Identification of risk factors (thyroid dysfunction, high level of thyroid-stimulating hormone (TSH) receptor antibodies, cigarette smoking) allows the identification of patients at risk and the institution of concomitant glucocorticoid treatment, thereby hindering progression of eye disease.On the basis, largely, of retrospective data, it appears that carbimazole (or methimazole), if stopped 3-5 days before treatment, does not influence the outcome of 131 I therapy. Simultaneous thyrostatic medication most probably reduces the efficacy of 131 I, as does restarting it within 7 days. Propylthiouracil seems to have a more prolonged radioprotective effect than carbimazole.Surgery is the treatment of first choice in patients with a large goitre. However, in the case of patient ineligibility or preference, 131 I therapy may be an option. The treatment has a favourable effect on tracheal compression and inspiratorycapacity, but the reduction in thyroid volume is only 30-40%. Inpatient treatment, necessitated by the large doses, makes the treatment cumbersome.Controversy related to radioiodine therapy is mainly based on the lack of adequate prospective randomised studies comparing efficacy, side effects, cost and patient satisfaction.

show abstract

Intrathyroidal Concentrations of Methimazole in Patients with Graves’ Disease*

Cited by 110 publications

References 16 publications

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues

Carbimazole Is an Inhibitor of Protein Synthesis and Protects from Neuronal Hypoxic Damage In Vitro

Controversies in radioiodine therapy: relation to ophthalmopathy, the possible radioprotective effect of antithyroid drugs, and use in large goitres

Contact Info

Product

Resources

About