An antithyroid agent is a
hormone antagonist ''For the use of hormone antagonists in cancer, see hormonal therapy (oncology)''
A hormone antagonist is a specific type of receptor antagonist which acts upon hormone receptors. Such pharmaceutical drugs are used in antihormone therapy.
External ...
acting upon
thyroid hormones.
The main antithyroid drugs are
carbimazole
Carbimazole (brand names Neo-Mercazole, Anti-Thyrox, etc.) is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from iodin ...
(in the UK),
methimazole (in the US), and
propylthiouracil (PTU). A less common antithyroid agent is
potassium perchlorate.
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
A randomized controlled trial (or randomized control trial; RCT) is a form of scientific experiment used to control factors not under direct experimental control. Examples of RCTs are clinical trials that compare the effects of drugs, surgical t ...
testing single dose treatment for Graves' found methimazole achieved euthyroid state more effectively after 12 weeks than did propylthiouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).
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
The thyrotropin receptor (or TSH receptor) is a receptor (and associated protein) that responds to thyroid-stimulating hormone (also known as "thyrotropin") and stimulates the production of thyroxine (T4) and triiodothyronine (T3). The TSH recep ...
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.
Competitive antagonists of thyroid stimulating hormone receptors are currently being investigated as a possible treatment for Grave's disease.
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.
/ref> Others include neutropenia, granulocytopenia (dose dependent, which improves on cessation of the drug) and aplastic anemia, and—for propylthiouracil—severe, fulminant liver failure.peripheral neuritis
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
. These drugs also cross the placenta
The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
and are secreted in breast milk. Lugol's iodine is used to block hormone synthesis before surgery.
Mechanism of action
The mechanisms of action are not completely understood. Some scientists believe that anti-thyroids inhibit iodination of tyrosyl residues in thyroglobulin
Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment ...
. 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
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
. Propylthiouracil additionally may reduce the de-iodination of T4 into T3 in peripheral tissues.
See also
* H03B code of antithyroid preparations
References
External links
*
{{Thyroid hormone receptor modulators
Antithyroid drugs