Euthyroid with high TBG occurs in which situations?

• A. Estrogen therapy, pregnancy, inflammation
• B. Nephrotic syndrome
• C. Cirrhosis
• D. Hyperparathyroidism

Answer: (A)

Thyroxine-binding globulin (TBG) is a liver-made protein that carries thyroid hormones in the blood. When TBG levels rise, more thyroid hormone is bound, so total T4 and T3 increase, but the free (unbound) hormone stays normal, leaving the person clinically euthyroid. Estrogenic states stimulate the liver to produce more TBG, so estrogen therapy increases TBG levels. Pregnancy also markedly raises TBG because of high estrogen levels. In some inflammatory or acute-phase states, TBG production can rise as part of the liver’s response, contributing to higher total thyroid hormone with normal free hormone.

In contrast, conditions like nephrotic syndrome cause loss of proteins (including TBG) in the urine, reducing TBG and lowering total thyroid hormones despite a normal or near-normal free fraction. Cirrhosis can alter hepatic protein synthesis and binding protein levels in various ways, not typically raising TBG. Hyperparathyroidism does not directly affect TBG. Therefore, the scenarios that produce euthyroid physiology with high TBG are estrogen therapy, pregnancy, and inflammation.