Thyroxine-Binding by Serum Protein in Pregnancy and in the Newborn

Abstract

Thyroid structure and function in man undergo a number of changes during pregnancy. The thyroid gland may become enlarged and hyperplastic (1, 2), thyroidal uptake of radioiodine is increased (3, 4), "conversion" of blood iodide to organic form is more rapid (4), and the serum proteinbound iodine (PBI) is elevated (5, 6). Although these alterations are like those seen in hyperthyroidism, they appear to be associated, in early pregnancy at least, with an unequivocally euthyroid state. Whereas the PBI rises as early as the first or second month of gestation, and remains at about the same level throughout pregnancy, elevation of the basal metabolic rate (2, 7) begins in the latter half of pregnancy and rises progressively. Circulatory changes, such as increased cardiac output (8), may precede the rise in oxygen consumption but these also change progessively until shortly before term.It has been postulated that alterations in the interaction of thyroid hormone with serum proteins might provide an explanation for these paradoxical findings (6). Inasmuch as circulating thyroxine is largely bound to what appears to be a specific alpha globulin (TBP) (9, 10), attention has been directed toward this protein in pregnancy. It has been demonstrated that TBP in pregnancy has an increased ability to complex thyroxine (10-13).In the present study, the thyroxine-binding capacity of TBP has been quantitated during the course of normal pregnancy and in newborn infants. From these data it has been possible to calculate an approximate concentration of free thyroxine in the serum of these subjects. METHODSSerum was obtained from 16 women during and after uncomplicated pregnancies, usually after an overnight fast, from umbilical vein blood sampled at delivery in three subjects, and from external jugular venipuncture in two infants on the third day after delivery. Mixtures of serum with I13'-labeled L-thyroxine 1 were prepared according to the procedure described previously (14). Prior to use, each of the eight thyroxine preparations employed was tested for radiochemical purity by chromatography, and was repurified, when necessary, to a purity of 90 per cent or better by an extraction procedure (15). Iodine analyses2 were performed by a modification of the method of Zak, Willard, Myers, and Boyle (16). The thyroxine-serum mixtures were subjected to zone electrophoresis on filter paper strips, using barbital buffer, pH 8.6, ionic strength 0.1, and a "reverse-flow" technique (15). This modification of the electrophoresis procedure avoided the inclusion of albumin-bound thyroxine in the alpha globulin zone.For measurement of the thyroxine-binding capacity of TBP, the quantity of thyroxine added to each serum was sufficient to effectively saturate the thyroxine-binding sites on TBP. Actual saturation of these sites is approached asymptotically (15). Analysis of data obtained with normal sera (10), however, had indicated that the amount of thyroxine associated with alpha globulin reaches an effective plateau when less than 60 per cent of t...

Serum Triiodothyronine, Total Thyroxine, and Thyroxine to Triiodothyronine Ratios in Paired Maternal-Cord Sera and at One Week and One Month of Age

“…in maternal blood are in accordance with the reports of other investigators who have found these changes to be characteristic of pregnancy [16,20,22]. The increase in TBG cap.…”

Thyroid Function Studied in Paired Maternal-Cord Sera and Sequential Observations of Thyrotropic Hormone Release during the First 72 Hours of Life

“…Some investigators have found higher mean Plil and bulanol-extracted iodine values in maternal blood at delivery than in cord blood [3, fi, 10, 18]. while others have found no dilference [2,9,17,22,23,25]. We have shown that maternal blood thyroxine levels are slightly, but significantly, higher than those in cord samples.…”

“…), 21,25]; others have found values comparable to those of maternal serum [3]. Because FT., is calculated as the product of total thyroxine and FT.,F in serum, the discrepancies in FT 4 reported from different laboratories can partly be explained by clillerent methods used to estimate thyroxine in serum.…”

11 Hypothyroidism in Pregnancy

“…This increase in TBG level is due to the increase in estrogen concentration, resulting in a rise of TBG production and release by the liver, site of synthesis of the protein [11]. Furthermore, the circulating levels of both albumin and prealbumin remain stable, with only a discrete tendency to decrease near term, consequently to the hemodilution [13]. The respective affinities of the three binding proteins for TH are not significantly modified.…”