Antithyroid agent

Source: Wikipedia, the free encyclopedia.

An antithyroid agent is a

thyroid hormones
.

The main antithyroid drugs are

methimazole (in the US), and propylthiouracil (PTU). A less common antithyroid agent is potassium perchlorate
.

Classification based on mechanisms of action

The mechanisms of action of antithyroid drugs are not completely understood. Based on their mechanisms of action, the drugs are classified into following six classes.

Thyroid hormone synthesis inhbitors

These drugs probably inhibit the enzyme

iodination of tyrosyl residues in thyroglobulin, and coupling of iodotyrosyl and iodothyronyl residues.[1] 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. The most common drugs in this class are thioamides, which include propylthiouracil, methimazole and its prodrug
carbimazole.

Additionally, propylthiouracil may reduce the de-iodination of

thyroxine (tetraiodothyronine; T4) into triiodothyronine (T3) in peripheral tissues.[2]

thyroid gland).[4]

Iodide uptake inhibitors

They decrease uptake of

transporter protein that co-transports Na+ and I− ions. Iodide transport is a key step in the biosynthesis of the thyroid hormones T4 and T3.[5][6] For example, potassium perchlorate competitively inhibits the active iodide transport mechanism in the thyroid gland, which has the capacity to selectively concentrate iodide against a large concentration gradient.[5][6]

Besides perchlorates, other examples of iodide uptake inhibitors include pertechnetates, thiocyanates, nitrates.[7]

These drugs are no longer used due to high toxicity and adverse effects.[8][9]

Thyroid hormone release inhibitors

They inhibit release (secretion) of thyroid hormones by the thyroid gland. The most studied drug in this class is lithium, which inhibits thyroid hormone secretion by inhibiting iodotyrosine coupling, thyroidal iodide uptake, and alteration in structure of thyroglobulin,[10] a protein which acts as a substrate for the synthesis of thyroid hormones and storage of inactive forms of T3, T4 and iodine within the lumen of thyroid follicular cells.[11] Since lithium is neither metabolized nor protein-bound, its bioavailability usually is close to 100%.[12] Hence, there are risks of serious side effects such as lithium toxicity, hypothyroidism, and diabetes insipidus.[13]

Excess iodine

Excessive iodine intake can temporarily inhibit production of thyroid hormones. This occurs because of the

Wolff-Chaikoff effect, which is a phenomenon of rejection of large quantities of iodine by the thyroid gland, therefore preventing it from synthesizing large quantities of thyroid hormones.[14]

Iodine radiopharmaceuticals

Main articles: Isotopes of iodine and radiopharmaceutical

They are

thyroid tumors.[15]

Thyroid hormone receptor antagonists

Also called TR antagonists, they inhibit action of thyroid hormones by blocking

coactivator interaction inhibitors, which interfere with the interaction between TR receptors and coactivator proteins such as nuclear hormone receptor coregulator (NRC). As a result, the receptors are unable to recruit coactivators, causing stoppage of transcription of target genes, thereby preventing activation of TR receptors, ultimately leading to inhibition of effects of thyroid hormones because they can bind to only inactive TR receptors, and these receptors can't be activated in presence of TR antagonists.[18] Antagonist 1-850 has also been found to inhibit binding of [125I]T3[a] to TRs in intact GH4 cells.[18]

Adverse effects

The most dangerous side effect is

idiosyncratic reaction which generally resolves on cessation of drug. It occurs in about 0.2 to 0.3% of cases treated with antithyroid drugs.[19] Other side effects include granulocytopenia (dose dependent, which improves on cessation of the drug) and aplastic anemia, and in case of propylthiouracil, severe, fulminant liver failure.[20]
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.[21] These drugs also cross the placenta and are secreted in breast milk.[22]

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 euthyroidism (normal thyroid function that occurs within normal serum levels of TSH and T4[23]) more effectively after 12 weeks than did propylthiouracil (77.1% on methimazole 15 mg vs 19.4% in the propylthiouracil 150 mg groups).[24]
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

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.[25]

Competitive antagonists of thyroid stimulating hormone receptors are currently being investigated as a possible treatment for Grave's disease.

See also

Notes

  1. ^ [125I]T3 is a radiopharmaceutical formulation of triiodothyronine having iodine-125 atoms instead of iodine.

References

  1. ^ "Thioamide - an overview | ScienceDirect Topics". www.sciencedirect.com. Archived from the original on 2023-09-27. Retrieved 2023-10-03.
  2. PMID 23883148
    .
  3. PMID 17389702
    .
  4. PMID 16763249
    .
  5. ^ a b Furman, B. L. "Potassium Perchlorate - an overview | ScienceDirect Topics". www.sciencedirect.com. Archived from the original on 2023-10-03. Retrieved 2023-10-03.
  6. ^
    PMID 9549759
    .
  7. PMID 26151950
    .
  8. PMID 13060263
    .
  9. PMID 36339434
    .
  10. PMID 9827658
    .
  11. ^ "TG thyroglobulin [Homo sapiens (human)] – Gene – NCBI". National Center for Biotechnology Information (NCBI). Retrieved 2019-09-16.
  12. PMID 29955448
    .
  13. ^ "Lithium Salts". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 1 December 2015.
  14. PMID 11396709
    .
  15. ^ a b "Iodide I-131". go.drugbank.com. Retrieved 2023-10-03.
  16. PMID 31945059
    .
  17. PMID 32644740
    , retrieved 2023-10-03
  18. ^
    PMID 12777627
    .
  19. PMID 16446945
    .
  20. PMID 19583480
    .
  21. ISSN 0973-0354
    .
  22. S2CID 33852149
    .
  23. ^ "Euthyroidism - an overview | ScienceDirect Topics". www.sciencedirect.com. Archived from the original on 2023-10-03. Retrieved 2023-10-03.
  24. S2CID 24463399
    .
  25. PMID 11331213
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Antithyroid_agent&oldid=1190260440"