A 32-year-old woman comes to the office due to neck swelling. The patient says her neck has gradually gotten larger, and she does not like how it appears in the mirror. She otherwise feels well and has no hoarseness, trouble swallowing, or shortness of breath. There is no history of head and neck irradiation. The patient has no prior medical conditions and takes no medications. She has a sister with vitiligo. Blood pressure is 110/60 mm Hg and pulse is 75/min. On physical examination, the thyroid is diffusely enlarged with no palpable nodules. There is no tracheal deviation. Serum TSH and free thyroxine levels are normal. Antibodies against thyroid peroxidase are present in high titers. The antigenic target of these antibodies is involved in which of the following processes?

Question

A 32-year-old woman comes to the office due to neck swelling.  The patient says her neck has gradually gotten larger, and she does not like how it appears in the mirror.  She otherwise feels well and has no hoarseness, trouble swallowing, or shortness of breath.  There is no history of head and neck irradiation.  The patient has no prior medical conditions and takes no medications.  She has a sister with vitiligo.  Blood pressure is 110/60 mm Hg and pulse is 75/min.  On physical examination, the thyroid is diffusely enlarged with no palpable nodules.  There is no tracheal deviation.  Serum TSH and free thyroxine levels are normal.  Antibodies against thyroid peroxidase are present in high titers.  The antigenic target of these antibodies is involved in which of the following processes?

Quizplus · Accepted Answer

11ec160b_3cb1_d01b_9249_cde39dc0ce5b_MD0001_00 Thyroid follicular cells take up iodide (I⁻), which is then transported into the thyroid follicular lumen, where it is oxidized to iodine (I₂). Following oxidation, in a process referred to as organification, iodine reacts with tyrosine residues in thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT) (iodination). While still attached to thyroglobulin, DIT and MIT participate in 2 coupling reactions: The coupling of 2 DITs results in formation of thyroxine (T4); the combination of 1 DIT and 1 MIT leads to the formation of triiodothyronine (T3). Subsequently, thyroglobulin, which is now attached to multiple iodinated tyrosine compounds (ie, MIT, DIT, T3, T4), is engulfed by the thyroid follicular cells and digested within lysosomes, releasing T3 and T4 into the circulation. Free DIT and MIT are also produced, but only small amounts are secreted because iodotyrosine deiodinase removes the iodine groups from MIT and DIT for recycling (Choice B). Thyroid peroxidase (TPO) is a multifunctional enzyme that catalyzes the oxidation of iodide, the iodination of thyroglobulin, and the coupling reaction between 2 iodized tyrosine residues. Antibodies against TPO can be seen in a variety of autoimmune thyroid disorders, most commonly chronic lymphocytic (Hashimoto) thyroiditis (90% of patients). Hashimoto thyroiditis is a common cause of diffuse goiter, as in this patient. Although most patients develop residual hypothyroidism (low T4, elevated TSH), early in the disease they may be euthyroid (normal T4, normal TSH) or briefly hyperthyroid (elevated T4, suppressed TSH). (Choice A) Uptake of iodide from the blood against its concentration gradient is an energy-dependent process carried out by the sodium-iodide symporter and stimulated by TSH. TPO is not involved in iodide uptake. (Choice D) Thyroglobulin is a high-molecular-weight, glycosylated protein that is the major component of colloid in the thyroid follicle. TPO is involved in iodination, but not synthesis of thyroglobulin. (Choice E) As noted above, the thyroid produces both T3 and T4, although most is in the form of T4. T3, the more active form of thyroid hormone, is produced primarily in peripheral tissues by deiodination of T4. This reaction is catalyzed by iodothyronine deiodinase, not by TPO. Educational objective: Thyroid peroxidase (TPO) catalyzes the oxidation of iodide to iodine, the iodination of thyroglobulin tyrosine residues, and the iodotyrosine coupling reaction that forms T3 and T4. Antibodies against TPO are present in >90% of patients with chronic lymphocytic (Hashimoto) thyroiditis.

A 32-Year-Old Woman Comes to the Office Due to Neck