Antithyroid agent
Encyclopedia
An antithyroid agent is a hormone antagonist
acting upon thyroid hormone
s.
The main antithyroid drugs are carbimazole
(in the UK), methimazole
(in the US), and propylthiouracil
/PTU. A less common antithyrioid agent is potassium perchlorate
.
s.
(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. Others include granulocytopenia
(dose dependent, which improves on cessation of the drug) and aplastic anemia
, and for propylthiouracil
severe, fulminant liver failure. 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.
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). 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.
Hormone antagonist
For the use of hormone antagonists in cancer, see hormonal therapy A Hormone antagonist is a specific type of receptor antagonist which acts upon hormones....
acting upon thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s.
The main antithyroid drugs are carbimazole
Carbimazole
Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents the thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the...
(in the UK), methimazole
Methimazole
Methimazole is an antithyroid drug, and part of the thioamide group.-Indications:...
(in the US), and propylthiouracil
Propylthiouracil
Propylthiouracil or 6-n-Propylthiouracil is a thioamide drug used to treat hyperthyroidism by decreasing the amount of thyroid hormone produced by the thyroid gland...
/PTU. A less common antithyrioid agent is potassium perchlorate
Potassium perchlorate
Potassium perchlorate is the inorganic salt with the chemical formula KClO4. Like other perchlorates, this salt is a strong oxidizer and potentially reacts with many organic substances...
.
Mechanism of action
Carbimazole, methimazole and propylthiouracil inhibit the enzyme thyroperoxidase, and thereby block the binding of iodine and coupling of iodotyrosines, in turn causing reduced synthesis of thyroid hormoneThyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s.
Adverse effects
The most dangerous side-effect is agranulocytosisAgranulocytosis
Granulopenia, also known as Agranulosis or Agranulocytosis, is an acute condition involving a severe and dangerous leukopenia , most commonly of neutrophils causing a neutropenia in the circulating blood. It represents a severe lack of one major class of infection-fighting white blood cells...
(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. Others include granulocytopenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
(dose dependent, which improves on cessation of the drug) and aplastic anemia
Aplastic anemia
Aplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. The condition, per its name, involves both aplasia and anemia...
, and for propylthiouracil
Propylthiouracil
Propylthiouracil or 6-n-Propylthiouracil is a thioamide drug used to treat hyperthyroidism by decreasing the amount of thyroid hormone produced by the thyroid gland...
severe, fulminant liver failure. 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
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
and are secreted in breast milk
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
. Lugol's iodine is used to block hormone synthesis before surgery.
Usage in Grave's disease
In Grave's 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). 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
Thyrotropin receptor
The thyrotropin receptor is a receptor that responds to thyroid-stimulating hormone and stimulates the production of thyroxine and triiodothyronine...
antibodies (TSHR-Ab) and smoking. A positive TSHR-Ab at the end of antithyroid drug treatment increases the risk of recurrence to 90% (sensitivity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
39%, specificity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
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.