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a substance that exerts some force or effect
a businessman who buys or sells for another in exchange for a commission (同)factor, broker
any agent or representative of a federal agency or bureau (同)federal agent
a representative who acts on behalf of other persons or organizations
an active and efficient cause; capable of producing a certain effect; "their research uncovered new disease agents"
how long something has existed; "it was replaced because of its age"
a time of life (usually defined in years) at which some particular qualification or power arises; "she was now of school age"; "tall for his eld" (同)eld
begin to seem older; get older; "The death of his wife caused him to age fast"
make older; "The death of his child aged him tremendously"
having the effect of counteracting excessive thyroid activity; "antithyroid drugs"

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『代理人』;周旋人 / 働き(作用)を起こすもの;作用物,薬剤 / (政府機関,特にFBI,CIAなどの)部員,機関員
〈U〉(一般に)『年齢』,寿命;〈C〉(個々の)『年齢』,年 / 〈U〉成年(おとなとしての資格・権利を得る年齢;通例18または21歳) / 〈U〉『老齢』;《集合的に》老人たち / 〈U〉(人生の)『一時期』;〈C〉世代(generation) / 〈U〉〈C〉《しばしばA-》(歴史上の)『時代』 / 〈C〉《話》長い間 / 年をとる,ふける;〈物が〉古くなる / 〈年〉'を'とらせる;〈物〉'を'古びさせる

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/01/08 21:57:20」(JST)

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An antithyroid agent is a hormone antagonist acting upon thyroid hormones.

The main antithyroid drugs are carbimazole (in the UK), methimazole (in the US), and propylthiouracil/PTU. A less common antithyroid agent is potassium perchlorate.

Mechanism of action

The mechanisms of action are not completely understood. Some scientists believe that anti-thyroids inhibit iodination of tyrosyl residues in thyroglobulin. It is thought that they inhibit the thyroperoxidase catalyzed oxidation reactions by acting as substrates for the postulated peroxidase-iodine complex, thus competitively inhibiting the interaction with the amino acid tyrosine. Propylthiouracil additionally may reduce the de-iodination of T4 into T3 in peripheral tissues.^[1]

Adverse effects

The most dangerous side-effect is agranulocytosis (1/250, more in PTU); this is an idiosyncratic reaction which generally resolves on cessation of drug. It occurs in about 0.2 to 0.3% of cases treated with antithyroid drugs.^[2] Others include granulocytopenia (dose dependent, which improves on cessation of the drug) and aplastic anemia, and for propylthiouracil severe, fulminant liver failure.^[3] Patients on these medications should see a doctor if they develop sore throat or fever.

The most common side effects are rash and peripheral neuritis. These drugs also cross the placenta and are secreted in breast milk. Lugol's iodine is used to block hormone synthesis before surgery.

Usage in Graves' disease

In Graves' disease, treatment with antithyroid medications must be given for six months to two years, in order to be effective. Even then, upon cessation of the drugs, the hyperthyroid state may recur. Side effects of the antithyroid medications include a potentially fatal reduction in the level of white blood cells.

A randomized control trial testing single dose treatment for Graves' found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthyouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).^[4] But generally both drugs are considered equivalent.

A study has shown no difference in outcome for adding thyroxine to antithyroid medication and continuing thyroxine versus placebo after antithyroid medication withdrawal. However, two markers were found that can help predict the risk of recurrence. These two markers are an elevated level of thyroid stimulating hormone receptor antibodies (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (sensitivity 39%, specificity 98%), a negative TSHR-Ab at the end of antithyroid drug treatment is associated with a 78% chance of remaining in remission. Smoking was shown to have an impact independent to a positive TSHR-Ab.^[5]

References

^ Manna D, Roy G, Mugesh G (2013). "Antithyroid Drugs and their Analogues: Synthesis, Structure and Mechanism of Action". Acc. Chem. Res. 11: 2706–15. doi:10.1021/ar4001229. PMID 23883148.
^ Zambrana, J.; Zambrana, F.; Neto, F.; Gonçalves, A.; Zambrana, F.; Ushirohira, J. (2005). "Agranulocytosis with tonsillitis associated with methimazole therapy". Brazilian journal of otorhinolaryngology 71 (3): 374–377. PMID 16446945. edit [1]
^ Bahn, RS, Burch, HS, Cooper, DS, Garber, JR, Greenlee, CM, Klein, IL, Laurberg, P, McDougall, IR et al. (July 2009). "The Role of Propylthiouracil in the Management of Graves' Disease in Adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration.". Thyroid : official journal of the American Thyroid Association 19 (7): 673–4. doi:10.1089/thy.2009.0169. PMID 19583480.
^ Homsanit M, Sriussadaporn S, Vannasaeng S, Peerapatdit T, Nitiyanant W, Vichayanrat A (2001). "Efficacy of single daily dosage of methimazole vs. propylthiouracil in the induction of euthyroidism". Clin. Endocrinol. (Oxf) 54 (3): 385–90. doi:10.1046/j.1365-2265.2001.01239.x. PMID 11298092.
^ Glinoer D, de Nayer P, Bex M (2001). "Effects of l-thyroxine administration, TSH-receptor antibodies and smoking on the risk of recurrence in Graves' hyperthyroidism treated with antithyroid drugs: a double-blind prospective randomized study". Eur. J. Endocrinol. 144 (5): 475–83. doi:10.1530/eje.0.1440475. PMID 11331213.

External links

Antithyroid agents at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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English Journal

Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?

Weetman AP.Author information Department of Human Metabolism, Faculty of Medicine Dentistry and Health, The Medical School, University of Sheffield, Sheffield, UK.AbstractGraves' disease and other disorders of thyroid function may occur following treatment with novel anticancer agents or during periods of lymphocyte recovery after lymphopenia. There are three main settings for such lymphocyte reconstitution: recovery after a bone marrow or haematopoietic stem cell transplant, alemtuzumab treatment and the use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus infection. The available evidence suggests that Graves' disease behaves as normal in most of these cases and should be treated conventionally, but it may follow a more favourable course in those receiving alemtuzumab or HAART. As spontaneous or drug-induced remission may be more likely in these two settings, first-line treatment should usually consist of an antithyroid drug.
Clinical endocrinology.Clin Endocrinol (Oxf).2014 May;80(5):629-32. doi: 10.1111/cen.12427.
Graves' disease and other disorders of thyroid function may occur following treatment with novel anticancer agents or during periods of lymphocyte recovery after lymphopenia. There are three main settings for such lymphocyte reconstitution: recovery after a bone marrow or haematopoietic stem cell tr
PMID 24528193

Images in clinical medicine. Neonatal thyrotoxicosis.

Bisschop PH1, van Trotsenburg AS.
The New England journal of medicine.N Engl J Med.2014 Mar 27;370(13):1237. doi: 10.1056/NEJMicm1308956.
PMID 24670170

Mechanistic analysis of metabolomics patterns in rat plasma during administration of direct thyroid hormone synthesis inhibitors or compounds increasing thyroid hormone clearance.

Montoya GA1, Strauss V1, Fabian E1, Kamp H1, Mellert W1, Walk T2, Looser R2, Herold M2, Krennrich G1, Peter E2, van Ravenzwaay B3.Author information 1BASF SE, Ludwigshafen, Germany.2metanomics GmbH, Berlin, Germany.3BASF SE, Ludwigshafen, Germany. Electronic address: bennard.ravenzwaay@basf.com.AbstractFor identification of toxicological modes of action (MoAs) a database (MetaMap(®)Tox) was established containing plasma metabolome consisting of approximately 300 endogenous metabolites. Each five male and female Wistar rats per groups were treated with >500 reference compounds over a period of 28 days. More than 120 specific toxicity patterns of common metabolite changes associated with unique MoAs were established. To establish patterns predictive effects on the thyroid, animals have been treated with reference compounds directly acting on the thyroid hormone formation (such as methimazole, ethylenethiourea) as well as liver enzyme inducers leading to an increased excretion of thyroid hormones and therewith to a secondary response of the thyroid (such as aroclor 1254 and boscalid). Here we present the plasma metabolite changes which form the patterns for direct and indirect effects on the thyroid. It is possible to identify metabolites which are commonly regulated irrespective of an indirect or direct effect on the thyroid as well as groups of metabolites separating both MoAs. By putting the metabolite regulations in the context of affected pathways helps to identify thyroid hormone inhibiting MoAs even when the hormone levels are not consistently changed. E.g., direct thyroid hormone synthesis inhibitors affect some enzymes in the urea cycle, increase the ω-oxidation of fatty acids and decrease glutamate and oxoproline levels, whereas indirect thyroid hormone inhibiting compounds interact with the lipid mediated and liver metabolism.
Toxicology letters.Toxicol Lett.2014 Mar 3;225(2):240-51. doi: 10.1016/j.toxlet.2013.12.010. Epub 2013 Dec 24.
For identification of toxicological modes of action (MoAs) a database (MetaMap(®)Tox) was established containing plasma metabolome consisting of approximately 300 endogenous metabolites. Each five male and female Wistar rats per groups were treated with >500 reference compounds over a period of
PMID 24370789

Japanese Journal

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日本口腔外科学会雑誌 59(12), 796-800, 2013
… He was immediately treated with a β -blocker, potassium iodide preparation, and antithyroid agent. …
NAID 130004793875

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高田昌彦,宮本良文
日本呼吸器外科学会雑誌 = The journal of the Japanese Association for Chest Surgery 24(1), 69-73, 2010-01-15
症例は30歳，女性．背部痛および胸骨部痛で近医を受診した際，胸部異常影を指摘され当科紹介受診となった．胸部CT上，前縦隔に腫瘤を認め，さらに甲状腺の腫大を認めた．血液検査でF-T4の上昇とTSHの低下を認め，甲状腺機能亢進症と診断した．前縦隔の腫瘤は，MRI上T1，T2強調像とも内部が均一に描出され，さらに化学シフトMRイメージングを撮影した所，in phaseT1強調像に比べ，out of ph …
NAID 10025954500