A 22-year-old woman comes to the office due to palpitations, weight loss, and insomnia. She has lost 7 kg (15.4 lb) in the past 3 months. The patient has no other medical problems and takes no medication. She does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/80 mm Hg and pulse is 104/min and regular. The thyroid gland is diffusely enlarged and nontender on palpation. Laboratory studies show markedly decreased serum TSH and elevated thyroxine levels. Methimazole monotherapy is initiated. Two months later, her symptoms had resolved. The treatment most likely improved this patient's condition by directly inhibiting which of the following processes?
Show Explanatory Sources
Thyroid follicular cells take up inorganic iodide (iodide trapping) against a concentration gradient using a sodium-iodide symporter. Iodide is then released into the thyroid follicular lumen, where it is oxidized to iodine radical by thyroid peroxidase. Iodine then binds to tyrosine residues (organification) in thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Coupling of MIT and DIT produces triiodothyronine (T3; MIT coupled with DIT) and thyroxine (T4; two DITs coupled). The thyroid follicular cells then engulf thyroglobulin, which contains the iodinated tyrosine compounds, via pinocytosis. In the thyroid cytoplasm, T3 and T4 (collectively, thyroid hormones) are removed from the rest of the thyroglobulin and secreted from the basolateral border.
This patient with elevated T4 and suppressed TSH has primary hyperthyroidism. Methimazole and propylthiouracil are thioamide drugs used for treating hyperthyroidism. They inhibit thyroid peroxidase, the enzyme responsible for both iodine organification and coupling of iodotyrosines. Propylthiouracil also decreases the peripheral conversion of T4 to the active hormone T3, although methimazole does not have this effect (Choice D).
(Choice A) Colloid is a gelatinous material in the follicular lumen that consists mainly of thyroglobulin. The production of colloid is regulated primarily by TSH; it is not dependent on thyroid peroxidase and is not inhibited by thioamides.
(Choice C) Iodide uptake is upregulated by TSH. Perchlorate and pertechnetate are competitive inhibitors of the sodium-iodide symporter.
(Choice E) Hyperthyroidism is characterized by increased sensitivity to catecholamines due to the thyroid hormone–mediated upregulation of beta-adrenergic receptors. Beta blockers help decrease the target organ effects of thyroid hormones, and certain ones (eg, propranolol) also decrease the peripheral conversion of T4 to T3.
Educational objective:
Thioamides (eg, methimazole, propylthiouracil) decrease the formation of thyroid hormones via inhibition of thyroid peroxidase, the enzyme responsible for both iodine organification and coupling of iodotyrosines. Propylthiouracil also decreases the peripheral conversion of T4 to T3.