Alterations in the thyroid metabolism of hypoxic, fasted, and chronically ill adults and older children have been described. We evaluated the effects of asphyxia on thyroidal indices of term newborns and compared them to those of a control population. Blood was drawn from the cord and then serially at 5 min and 3, 24, and 48 h after delivery in all patients. Seven term healthy newborns (group 1)increased their free thyroxine (FT4) concentrations significantly after delivery from a mean +/- SD baseline of 0.94 +/- 0.13 ng/dl in cord blood to a mean +/- SD peak of 2.6 +/- 0.6 ng/dl 48 h after delivery (p less than 0.001 at 3, 24, and 48 h), while their free triiodothyronine (FT3) levels increased from a mean +/- SD baseline level of 2.3 +/- 0.5 pg/ml in cord blood to a mean +/- SD peak of 3.7 baseline level of 2.3 +/- 0.5 pg/ml 48 h after delivery (p less than 0.001 at 24 and 48 h). Seven term newborns with transient low Apgar scores at birth (group 2) and seven term neonates born to mothers with toxemia or hypertension (group 3) failed to increase their FT4 and FT3 concentrations above baseline during the first 48 h of life. FT4 and FT3 values at 3, 24, and 48 h were significantly higher in the control group than in groups 2 and 3. Cord blood thyroid-stimulating hormone, FT4, and FT3 levels were not statistically different in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

As a model of the changes in peripheral iodothyronine metabolism that occur during ontogeny, we have studied the metabolism of 125I-labeled T4 and several of its partially deiodinated derivatives by the liver of the chick embryo. Homogenates of livers obtained from chicks varying in embryonic age from 8 days to the time of hatching (20-21 days) were incubated with various iodothyronines, all labeled with 125I in their outer or phenolic ring. Rates and products of the reactions were analyzed by paper chromatography of whole homogenates. In livers from embryos of all ages studied, the addition of dithiothreitol (DTT; 2 mM) enhanced the rate of metabolism of the iodothyronines T4, T3, and rT3. Marked age-related changes in the metabolism of the iodothyronines were apparent; these were evident in the absence of DTT, but were most clearly seen in specimens to which DTT had been added. rT3 was degraded very rapidly, even in livers from 8-day-old embryos, but its rate of degradation increased progressively with increasing age of the embryo up to the time of hatching. Outer ring (5'-) monodeiodination, giving rise to 3,3'-diiodothyronine (3,3'-T2), was the predominant, and perhaps the sole, pathway of rT3 metabolism throughout this period of embryogenesis. Age-related changes in the metabolism of T4 and T3 were similar to one another, but differed greatly from those seen in the case of rT3. In specimens enriched with DTT, the rates of metabolism of T4 and T3 were moderately rapid in livers from 12-day-old embryos and then increased abruptly, remaining very rapid in livers from embryos through 18 days of age. Rapid degradation of T4 was not due to 5'-monodeiodination, since very little T3 was generated from T4. In addition, since results obtained were similar during incubations under air and N2, oxidative degradation of T4 was apparently not important. Rather, during this period, inner ring (5-) monodeiodination appeared to be by far the predominmant pathway of metabolism of both T4 and T3, leading to the formation of rT3 from T4 and 3,3'-T2 from T3. In livers from 19- and 20 day-old embryos, the latter obtained just before hatching, the overall metabolism of both T4 and T3 slowed abruptly and progressively owing to a decrease in the rate of 5-monodeiodination. Concomitantly, 5'-monodeiodination of T3 and T4 became more prominent, leading to increased generation of T3 from T4. These maturational changes in T4 and T3 metabolism coincided in time with penetration of the air sac by the embryo's beak and initiation of air breathing, a process termed internal pipping. Premature maturational changes in T4 and T3 metabolism, very similar to those that occurred spontaneously in 19- and especially 20-day-old embryos, were induced within 2 days by the single injection of 200 microgram hydrocortisone onto the allantoic membrane of immature embryos. It is concluded that hepatic iodothyronine metabolism in the immature embryo is directed so as to prevent the accumulation of T3 derived from T4...

All levels of the growth hormone (GH), GH binding protein (GHBP), insulinlike growth factor (IGF) and IGF binding protein (IGFBP) axis are influenced by chronic hypercortisolism. Thus, there is a blunted response to GHRH alone or together with other stimuli associated with a marked suppression of endogenous GH secretion but accompanied by normal GHBP, normal to low IGF-1 and GHBPs 1 and 3 with the correspondent 41.5 and 38.5-kD molecular forms of the latter presenting values similar to normal. These findings may suggest enhanced GH sensitivity with normal or increased IGF-1 bioavailability to the correspondent tissue receptors. In conclusion, the glucocorticoid (GC)-induced target tissue resistance can neither be attributed to the suppression of the GH axis nor to changes in circulating GHBPs 1 and 3. However, it may be related either to the described 12- to-20-kD inhibitor(s) which antagonizes postbinding IGF-1 bioactivity (gene expression) and/or by the downmodulation of activator protein-1 (Fos/Jun) activity by the GC-GC receptor complex.

Immunoglobulin G (IgG) fractions prepared from the serum of patients with Graves' disease (Graves'-IgG) are generally capable of inhibiting the binding of 125 I-labeled bovine TSH ([ 125 I]bTSH) to crude preparations of human thyroid membranes [TSH binding inhibitory (TBI) activity]. In current TBI assays, membranes, [ 125 I]bTSH, and IgG are incubated together, and the extent of inhibition of [ 125 I]bTSH binding produced by Graves'-IgG is compared with that produced by specimens of normal IgG. Such direct TBI assays, as we term them, have only moderate sensitivity, positive results being reported in approximately 50-75% of the actively thyrotoxic patients with Graves' disease. This appears to be owing to the wide ranging and often substantial TBI activity displayed by preparations of normal IgG.Reasoning that the TBI activity of normal IgG might be more readily dissociable from the thyroid membranes than the IgG specific for Graves' disease would be, we modified the TBI assay by first incubating the membranes with or without IgG, washing them thoroughly with buffer, and then incubating them with [ 125 I]bTSH. We term this a residual TBI assay, since it tests the extent of TBI activity that remains associated with the membranes despite the washing procedure. This procedure greatly reduced or eliminated the TBI activity of normal IgG and yielded a 94% frequency of positive responses in studies of 50 specimens of Graves'-IgG. In 31 specimens so tested, values of the residual TBI assay correlated significantly with their ability to increase the cAMP concentration in human thyroid slices.Ensuing experiments were conducted to test the feasibility of applying the principle of the residual TBI assay to the assay of whole serum, rather than IgG. A modification of the washing procedure used in residual TBI assays of IgG was shown to greatly decrease the almost complete inhibitory activity of serum seen in direct TBI assay. In residual TBI assays of 35 specimens of whole serum from patients with Graves' disease, a 77% frequency of positive responses was observed. In 27 samples so studied, a significant correlation was observed between the TBI activity of Graves'-IgG and that of the sera from which they were prepared. Application of the residual assay principle affords promise of greatly simplifying and enhancing the sensitivity of TBI assays. (J Clin Endocrinol Metab 54: 552, 1982) I T IS generally agreed that the thyroid hyperfunction in Graves' disease results from the action on the thyroid of abnormal immunoglobulins (Igs) of the IgG class that interact with the thyroid plasma membrane. As judged from in vitro studies, this interaction variously results in an activation of adenylate cyclase and an inhibition of the binding of TSH to its specific receptor in the plasma membrane, possibly owing to binding of these IgG to the receptor itself. These responses form the basis for the two types of assay most commonly employed at present to detect these disease-specific IgGs. One