An unusual opportunity was afforded to study the effect of endogenous increase in estrogen on thyroxine binding globulin (TBG) throughout pregnancy in a partially TBG-deficient female who conceived subsequent to initial examination. TBG binding of 125I-thyroxine (T4) before and up to four months of pregnancy was low in comparison to normal. Starting from six months and up to the end of pregnancy, TBG activity showed a definite increase although still below normal. TBG binding capacity increased from a low value of 4.2 microgram T4/100 ml ,efore pregnancy to a value 9.3 microgram T4/100 ml in the last month of pregnancy. This was accompanied by an increase in immunoassayable TBG from less than 1 mg/100 ml in the second month of pregnancy to 1.9 mg/100 ml in the last month, and an increase of T4 from 3.1 microgrom/100 ml to 4.3 microgram/100 ml. Two weeks after delivery, TBG binding of 125I-T4 showed a precipitous decline to the abnormally low distribution noted prior to and during the early months of pregnancy. TBG binding activity was normal in the cord blood of the infant. These studies provide the first direct evidence that increase in endogenous estrogen results in detectable increases in TBG concentration in the human with partial TBG deficiency.

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