Question
An investigator is studying a drug that acts on the thyroid hormone pathway. Levels of serum free T3 and T4 in healthy participants are measured before and after administration of the drug. After administration, there is a decrease in the average serum free T3 level, while the average serum free T4 level is increased compared to initial serum studies. Inhibition of which of the following is the most likely mechanism of action of this drug?
| A. |
Follicular thyroid proteases
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| B. |
Thyroid-stimulating hormone
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| C. |
Follicular iodotyrosine deiodinase
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| D. |
Peripheral 5′-deiodinase
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Show Answer
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Correct Answer � D
Explanation
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Answer D. Peripheral 5′-deiodinase
This is the mechanism of action of propylthiouracil (PTU).
Peripheral 5′-deiodinase
Peripheral 5′-deiodinase converts the less potent T4 into the biologically active T3 (which binds nuclear receptors with significantly higher affinity than T4). Inhibition of 5′-deiodinase results in an increase in the average serum T4 level and a decrease in the average serum T3 level. Drugs that inhibit 5′-deiodinase, such as propylthiouracil, are used in patients with hyperthyroidism. PTU also inhibits thyroid peroxidase.
Follicular thyroid proteases
Thyroid follicular proteases release T3 and T4 from thyroglobulin so that they can enter peripheral circulation and reach peripheral tissues. Inhibition would decrease the average serum levels of both T3 and T4.
Thyroid-stimulating hormone
Thyroid-stimulating hormone (TSH) is synthesized in the anterior pituitary gland and stimulates the release of T3 and T4 from the thyroid gland. An inhibition of TSH (e.g., due to somatostatin) would decrease the average serum levels of both T3 and T4.
Follicular iodotyrosine deiodinase
By catalyzing the deiodination of monoiodotyrosine (MIT) and diiodotyrosine (DIT), iodotyrosine deiodinase is responsible for recycling free MIT and DIT and returning to T3 and T4 synthesis. Inhibiting iodotyrosine deiodinase would decrease the iodide available for thyroid hormone synthesis and therefore eventually decrease serum levels of both T3 and T4.
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