Support for the upregulation of serum thyrotropin by estrogens coming from the increased requirement of levothyroxine in one gynecomastic patient with excess of thyroxine-binding globulin secondary to exposure to exogenous estrogens

Abstract

Thyroxine-binding globulin (TBG) is the liver-synthesized and estrogen-upregulated major plasma carrier of thyroid hormones with an affinity binding greater for T4 than T3. It is known that pregnancy, a physiologic state of estrogen-driven elevation of serum TBG, raises the requirement of L-T4 dose in hypothyroid women, especially those with no residual thyroid function. Similar increased requirement was reported for postmenopausal women during estrogen therapy. One known cause of relative hyperestrogenemia, gynecomastia and acquired TBG excess is liver disease, but very rarely chronic liver disease is mentioned as a cause of increased L-T4 requirement. One hypothyroid man with cirrhosis-associated gynecomastia and increased serum levels of both estradiol and TBG was reported recently. His requirement of L-T4 was no longer increased after liver transplantation. We now report the case of a man with primary hypothyroidism under stable replacement therapy with L-T4 until exposure to an exogenous cause of hyperestrogenemia caused increased L-T4 requirement associated to TBG excess. In addition to increased TBG, the high levels of estrogens had caused the appearance of gynecomastia. We fully corrected primary hypothyroidism upon eliminating his exposure to the source of estrogens. Hyperestrogenism can be a cause of increased L-T4 requirement through the rise of circulating levels of TBG also in man with no residual thyroid function. Keywords: Thyroxine-binding globulin, Estrogens, Thyrotropin, Levothyroxine therapy, Refractory hypothyroidism