A 52-year-old, post-menopausal woman comes to the office for a follow-up appointment. Six months ago, the patient was evaluated for recurrent, brief episodes of excessive warmth and sweating, which were interfering with her usual activities. Thyroid hormone levels were normal, and the patient was subsequently diagnosed with menopausal hot flashes. Treatment with estrogen-containing hormone replacement therapy was begun with significant symptom improvement. She has no other medical conditions and takes no other medications. Which of the following most likely occurred in this patient as a result of her medication use?

Question

A 52-year-old, post-menopausal woman comes to the office for a follow-up appointment.  Six months ago, the patient was evaluated for recurrent, brief episodes of excessive warmth and sweating, which were interfering with her usual activities.  Thyroid hormone levels were normal, and the patient was subsequently diagnosed with menopausal hot flashes.  Treatment with estrogen-containing hormone replacement therapy was begun with significant symptom improvement.  She has no other medical conditions and takes no other medications.  Which of the following most likely occurred in this patient as a result of her medication use?

Quizplus · Accepted Answer

11ec160b_3bc0_4457_9249_61a3b9874c1d_MD0001_00 Circulating thyroid hormone consists of 2 fractions: an inert protein-bound fraction and a free fraction that is available to enter target cells via a carrier-mediated mechanism. More than 99% of circulating thyroid hormone is bound to plasma proteins, creating a large circulating reservoir of thyroid hormone. Thyroxine-binding globulin (TBG) accounts for approximately 70% of thyroid hormone binding with an additional share bound by albumin and transthyretin. An increase in estrogen activity (eg, pregnancy, oral contraceptive use, postmenopausal hormone replacement therapy) raises circulating TBG levels, causing a corresponding reduction in free T4 and T3 levels. In patients with a normal hypothalamic-pituitary-thyroid axis, this reduction will result in a transient increase in TSH, leading to increased thyroid hormone production until the additional TBG becomes saturated with thyroid hormone and free T4 and T3 levels are restored (ie, patients remain euthyroid). Therefore, an increase in the TBG level leads to an increase in total T4 and T3 (bound plus free fractions). (Choice A) Estrogen does not affect the peripheral conversion of T4 to T3. Medications that decrease the peripheral conversion of T4 to T3 include propylthiouracil, glucocorticoids, and nonselective beta blockers. (Choices B and C) Thyroid iodine uptake increases transiently due to the temporary rise in TSH that occurs with increased TBG synthesis. However, iodine uptake normalizes once the newly synthesized TBG becomes saturated with thyroid hormone and TSH returns to normal. (Choice D) Increased circulating TBG levels cause a transient drop in free T4 and T3 levels as the existing pool of thyroid hormone becomes more protein-bound. However, free T4 and T3 levels quickly normalize as the thyroid synthesizes an appropriate quantity of new thyroid hormone to saturate the additional TBG. Educational objective: An increase in estrogen activity, as seen in pregnancy or postmenopausal estrogen replacement therapy, increases the level of thyroxine-binding globulin. This leads to an increase in total thyroid hormone levels, but feedback control maintains normal levels of free (biologically active) thyroid hormone.

A 52-Year-Old, Post-Menopausal Woman Comes to the Office for a Follow-Up