CHANGES IN SERUM CONCENTRATIONS OF THYROID HORMONES AND THYROID HORMONE-BINDING PROTEINS DURING EARLY INFANCY Studies in Healthy Fullterm, Small-for-gestational Age and Preterm Infants Aged 7 to 240 Days

Abstract. Serum concentrations of thyrotropin (TSH), thyroxine (T₄), triiodothyronine (T₃), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were determined in 492 blood samples from 127 fullterm (FT), 91 small-for-gestational age (SGA) and 88 preterm (PT) healthy infants aged 7 to 240 days. Serum T ₄ decreased about 20% during the first month of life. In infants aged 7–49 days, serum T₄ concentrations were significantly lower in SGA than in FT infants, and even lower values were found in PT infants. Serum T ₃ increased 50–70% reaching maximal values by 50–79 days of life. Serum T₃ levels were higher in FT than in SGA infants throughout the observation period. In PT infants serum T₃ increased from low values to levels which exceeded those of SGA and FT infants by 120–240 days of life. Serum TSH level did not change with age and was 5 mU/1 in all infants. Serum TBG values were high compared to normal adult values and did not change significantly with age. Comparable serum TBG values were found in FT, SGA and PT infants. Serum TBPA increased with age. Serum TBPA increased gradually in FT infants. In SGA infants serum TBPA increased from low values to levels which by 120–240 days of life exceeded those of PT and FT infants. In PT infants a decrease in serum TBPA appeared before the rise commenced. Serum Alb increased gradually in FT, SGA and PT infants during the observation period. Serum Alb in PT infants aged 30–119 days was lower than those in FT infants with similar ages. These physiological changes in serum concentrations of thyroid hormones and hormone-binding proteins during early infancy should be considered when interpreting thyroid function tests in infants with various maturity.     

Serum concentrations of thyrotropin, thyroid hormones and thyroid hormone-binding proteins during acute and recovery stages of idiopathic respiratory distress syndrome.

A total number of 27 premature infants with idiopathic respiratory distress syndrome (IRDS) and 52 healthy controls with comparable gestational age and body weights were studied during the first month of life. In infants with IRDS a reduced thyrotropin (TSH) response to birth was suggested, as serum TSH was lower in IRDS patients than in controls during the first two days of life. Low serum concentrations of thyroid hormones were found in the acute stage of IRDS reaching minimal values by day 3--5. After that period an increase in thyroid hormone levels occurred. The serum T2 increased to the level of healthy prematures by day 6--10, whereas the serum T4 increased to normal levels by day 21--30. Serum concentrations of thyroxine-binding globulin (TBG) were significantly lower in IRDS patients than in healthy controls; a gradual increase to normal levels occurred during recovery. Serum prealbumin (TBPA) levels in IRDS infants increased rapidly after birth and exceeded levels of healthy infants. Serum albumin values were not significantly different in the two groups of infants. The serum T4/TBG ratios were low during recovery from IRDS.     

Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants.

Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels were found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in fullterm, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was even lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

SERUM CONCENTRATIONS OF THYROXINE-BINDING GLOBULIN, PREALBUMIN AND ALBUMIN IN HEALTHY FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN INFANTS

Abstract. Jacobsen, B. B., Peitersen, B., Andersen, H. J. and Hummer, L. (The University Clinic of Paediatrics, Children's Hospital Fuglebakken and the Departments of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Serum concentrations of thyroxine-binding globulin, prealbumin and albumin in healthy fullterm, small-for-gestational age and preterm newborn infants. Acta Paediatr Scand, 68: 49, 1979.—Simultaneous serum concentrations of thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) were measured in 130 fullterm, 32 small-for-gestational age and 25 preterm infants during their first six days of life. In all infants serum concentrations of TBG were higher and serum TBPA and Alb were lower than in male adults. Even higher serum TBG levels wer found in the mothers. There was no correlation between serum concentrations in paired maternal and cord sera. In infants with birth weights appropriate for gestation serum TBG, TBPA, and Alb concentrations increased progressively with gestational age. In small-for-gestational age infants born at term serum concentrations of TBG and Alb were lower than those in full-term, but higher than those in premature newborns. Serum TBPA in small-for-gestational age babies was evne lower than seen in prematures. A positive correlation was found between thyroid hormones and TBG concentrations, not between serum TBPA and thyroid hormones. The ratios between serum concentration of thyroid hormones and proteins might indicate that more thyroid hormonebinding sites are occupied in fullterm than in low birth-weight newborns. However, the main reason for the different serum levels of thyroid hormones in fullterm, small-for-gestational age and preterm babies is probably the various serum TBG concentrations demonstrated in these infants.     

Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins

Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin (TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentration were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.     

Comparisons between serum concentrations of thyroxine and thyroxine-binding proteins in samples simultaneously obtained from capillary, peripheral vein, central vein and aorta in newborn infants.

A total number of 40 newborn infants with various maturity were studied: 13 babies without perinatal events, 19 infants recovered from transient diseases, 6 infants with idiopathic respiratory distress syndrome and 2 infants with asphyxia indicating artificial ventilation. Comparisons were performed between serum concentrations of thyroxine (T4), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) in capillary versus peripheral vein, aorta versus central vein and, finally, in peripheral versus central veins. In healthy infants serum T4 concentrations in capillary blood and peripheral vein did not differ significantly. Although serum concentrations of thyroid hormone-binding proteins tended to be increased in aortic compared to central venous specimens no statistically significant differences appeared. In infants in good clinical conditions serum T4, TBG, TBPA, and Alb levels were 6--8% higher in peripheral than in central veins, possibly primarily due to a hemo-concentrating effect of venous stasis. Therefore, in evaluation of the thyroid variables in newborn infants the technique of blood sampling must be considered. In most infants with idiopathic respiratory distress syndrome and in one asphyxiated baby a remarkable tendency to a low serum TBG and T4 concentration in peripheral compared to central vein samples were observed.     

SERUM CONCENTRATIONS OF THYROTROPIN, THYROID HORMONES AND THYROID HORMONE BINDING PROTEINS DURING ACUTE AND RECOVERY STAGES OF IDIOPATHIC RESPIRATORY DISTRESS SYNDROME

Abstract. A total number of 27 premature infants with idiopathic respiratory distress syndrome (IRDS) and 52 healthy controls with comparable gestational age and body weights were studied during the first month of life. In infants with IRDS a reduced thyrotropin (TSH) response to birth was suggested, as serum TSH was lower in IRDS patients than in controls during the first two days of life. Low serum concentrations of thyroid hormones were found in the acute stage of IRDS reaching minimal values by day 3–5. After that period an increase in thyroid hormone levels occurred. The serum T₃ increased to the level of healthy prematures by day 6–10, whereas the serum T₄ increased to normal levels by day 21–30. Serum concentrations of thyroxine-binding globulin (TBG) were significantly lower in IRDS patients than in healthy controls; a gradual increase to normal levels occurred during recovery. Serum prealbumin (TBPA) levels in IRDS infants increased rapidly after birth and exceeded levels of healthy infants. Serum albumin values were not significantly different in the two groups of infants. The serum T₄/TBG ratios were low during recovery from IRDS.     

Postnatal thyroid function in low birth weight infants: A cross-sectional assessment of free thyroxine and thyroid hormone binding globulin

To investigate the significance of low serum thyroxine in premature infants, serum FT4, T4, TSH and TBG were measured in 7 infants with BW<1000 g, 8 infants with BW 1001 to 1350 g, 9 infants with BW 1351 to 2499 g, and 11 full-term infants.FT4 concentrations were lower in the LBW infants than in the FT infants. Percent FT4 values in the infants with BW<1000 g were the highest in the groups studied, so that FT4 concentrations in those infants did not fall proportionally with the marked T4 decrease. TBG concentrations were lower in the VLBW infants (相似文献   

特发性肾病综合征患儿血清游离甲状腺激素检测的临床意义

探索特发性肾病综合症（ＩＮＳ）患儿血清游离甲状腺激素（ＴＨ）、甲状腺激素结合球蛋白（ＴＢＧ）的变化情况及其变化的机理和临床意义。对１６例ＩＮＳ患儿及１５例正常儿童对照,用放免法测Ｔ３、Ｔ４、ＦＴ３、ＦＴ４,化学发光酶免疫分析法测ＴＳＨ、ＴＢＧ,放射配基单点饱和饱和结合分析法测糖皮质激素受体（ＧＣＲ）。结果：①ＩＮＳ患儿Ｔ３、Ｔ４、ＦＴ３、ＦＴ４均低于对照组,ＴＳＨ升高,差异非常显著。②ＴＢＧ降低,ＴＢＧ与ＴＨ呈正相关。③ＩＮＳ患儿ＧＣＲ升高,ＴＨ与ＧＣＲ未见相关性。提示对糖皮质激素（ＧＣ）治疗敏感的ＩＮＳ患儿,虽然其ＴＨ是降低的,但其ＧＣＲ是升高的。     

Developmental changes in pituitary-thyroid function in the human fetus and newborn

Maturation of the hypothalamic pituitary thyroid axis as reflected in cord serum thyroid hormone concentrations was assessed in premature and full term infants born between 26 and 43 weeks gestation. Measurements of thyroxine (T4), free T4 (FT4), thyrotropin (TSH) and thyroxine binding globulin (TBG) in cord sera were correlated with gestational age, sex and birthweight and compared to similar measurements in well two month old infants and adults.There were significant increases in T4, FT4, and TBG with increasing gestational age (GA) between 26 and 33–35 weeks (P < 0.001). After 34 weeks, none of these parameters varied with GA. When the infants were separated on the basis of sex the linear regression curves describing the relationships between hormone and TBG concentrations and GA were not different from the curves in the total population. The mean FT4/TSH ratio increased significantly with age throughout gestation (P < 0.01) and was significantly lower in cord blood samples than in blood samples from the 2-month-old infants or the adults.The results suggest that the set point for negative feedback control of TSH secretion at the pituitary level is changing between 26 weeks GA and 2 months of life. Thyroid gland sensitivity to TSH stimulation also appears to be increasing between 26 and 33 weeks GA.     

SERUM LEVELS OF THYROTROPIN, THYROXINE AND TRIIODOTHYRONINE IN FULLTERM, SMALL-FOR-GESTATIONAL AGE AND PRETERM NEWBORN BABIES

Abstract. Simultaneous serum concentrations of TSH, total thyroxine (T₄) and triiodothyronine (T₃) were determined in 93 fullterm (FT), 37 small-for-gestational age (SGA) and 38 preterm (PT) babies with a postnatal age from 2 to 144 hours. In addition, TSH, T₄ and T₃ concentrations were measured in cord sera from 27 FT, 4 SGA and 5 PT babies and in venous blood from 20 mothers at delivery. Cord blood concentrations of TSH were higher and T₄ and T₃ concentrations were lower than seen in the mothers. Serum concentrations of TSH were high during the first day of life followed by a decline. There was no statistically significant difference between serum TSH concentrations of the three groups of newborns. On the 5th day of life no elevated serum TSH values were found in any of the groups (TSH<5mU/l). Serum concentrations of thyroid hormones increased after birth and reached maximum levels within 24 hours in all groups. The relative increases above cord level were of the same magnitude in the newborns: Two times for serum T₄ and six times for serum T₃. The thyroid hormone concentrations in blood samples from FT babies decreased from the second day of life, whereas in low birth weight newborns the decreases were more variable. The serum levels of T₄ and T₃ were significantly different in the three groups of newborns, the highest values were seen in FT and the lowest values in PT babies. In contrast, the ratios between molar serum concentrations of T₄ and T₃ were found to be highest in PT, lower in SGA and lowest in FT babies, approaching maternal values during the first week of life. The data are discussed with regard to hormone secretion, thyroxine-binding capacity and peripheral T₄ to T₃ conversion in the three groups of newborns. It is concluded that from day 5 after birth serum TSH determinations, alone or in combination with serum T₄, seem to be the method of choice in screening for congenital hypothyroidism.     

Thyroid function in thalassaemia major.

Serum concentrations of T4, T3, rT3, and TSH were measured by radioimmunoassay in 45 patients suffering from beta-thalassaemia. A TRH stimulation test was performed and the binding capacity of TBG and TBPA for T3 and T4 measured by reverse flow zone electrophoresis in a group of these patients. Mean T4 serum concentration was lower in thalassaemic patients than controls; T3, rT3, TSH levels, and the pituitary response to TRH were normal. TBPA binding capacity for thyroxine was greatly decreased, probably due to iron overload impairing the liver function. The decreased circulating total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration total thyroxine might be explained by the reduced TBPA capacity, serum free thyroid hormone concentration values being normal. It is concluded that thalassaemic children are euthyroid, despite often having low-normal or subnormal thyroxine levels.     

Thyroid function at birth in infants of 30 to 45 weeks' gestation.

Serum T4 was measured in cord blood of 2,683 infants of gestational ages 30 to 45 weeks and birth weights of 1,460 to 5,250 gm. In addition, serum TBG was measured in 180, and serum TSH in 125 of these infants. Mean serum T4 increased with gestational age from 9.4 microng/dl at 30 weeks to 11.7 at 45 weeks. TBG varied from 3.1 to 11.4 mg/dl but showed no correlation with gestational age. There was a positive correlation between T4 and TBG. Serum TSH levels showed a significant negative correlation with gestational age, decreasing from 15 micronU/ml at 30 weeks to 7 micronU/ml at 45 weeks, while the serum T4/TSH ratio increased from 0.6 to 1.6. The results indicate that cord, T4 varies mainly with TBG, and to a lesser extent with gestational age.     

THYROXINE-BINDING GLOBULIN DEFICIENCY IN EARLY CHILDHOOD

ABSTRACT. Jacobsen, B. B., Hansted, L. C, Brandt, N. J., Haahr, J., Hummer, L., Munkner, T. and Sorensen, S. S. (Department of Paediatrics, Viborg Hospital, Children's Hospital Fuglebakken, Department of Paediatrics, Section of Clinical Genetics and Department of Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark). Thyroxine-binding globulin deficiency in early childhood. Postnatal changes in serum concentrations of thyroid hormones and thyroid hormone-binding proteins. Acta Paediatr Scand, 70:155, 1981. –Serial determinations of serum thyroxine (T4), triiodothyronine (T3), thyrotropin(TSH), thyroid hormone-binding globulin (TBG), prealbumin (TBPA) and albumin were performed in a euthyroid girl with TBG deficiency and in her mother for a period of 22 months after delivery. At 8 days old the child had a serum TBG concentration around 50% of normal level which remained essentially unchanged during infancy. Total serum T4 and T3 concentrations were low, the free serum T4, free serum T3 and serum TSH concentrations were normal. The mother had received thyroid hormone from the age of 15 years. Her serum TBG level at 6 weeks post partum was similar to that of non-pregnant adults but decreased to about 50% of normal level, indicating a TBG deficiency. She remained euthyroid after withdrawal of T4 therapy. Serum TBPA and albumin concentrations were normal in mother and child. An X-linked inheritance of the TBG deficiency was suggested from a study of the family.     

Investigation of the relationship between low Apgar scores and early neonatal thyroid function

BACKGROUND: The aim of the present study was to assess the effects of low Apgar scores on perinatal thyroid function. METHODS: Forty full-term infants delivered by the normal spontaneous vaginal route were enrolled into the study. All babies had 1 and 5 min Apgar scores below 4. The control group consisted of 26 full-term healthy neonates. Cord blood and serum tri-iodothyronine (T3), thyroxine (T4), reverse tri-iodothyronine (rT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid-binding globulin (TBG) determinations were performed by an enzyme immunoassay method. RESULTS: The mean values of FT4 and T4 observed in the cord blood of the study group were significantly lower compared with matched controls, whereas the mean TSH values were significantly higher. There were no differences in concentrations of T3, rT3 and TBG between the two groups. CONCLUSIONS: These results demonstrate the existence of transient hypothyroidism at birth in babies with Apgar scores below 4 delivered by the spontaneous vaginal route.     

The thyroid hormone system in mucoviscidosis

Endocrine disorders do not represent primary manifestations in children with cystic fibrosis. Abnormal thyroid gland function is commonly observed in patients with chronic nonthyroidal illnesses. Serum concentrations of TSH, T4 and T3 were measured and a TRH-stimulation test (200 micrograms Relefact per kg body weight) was performed in 24 patients with CF 6 to 16 1/2 years of age. As compared to the controls, CF patients had increased basal TSH and lower T4 and T3 concentrations. Finally they exhibited higher TRH-stimulated TSH and decreased peripheral T4 and T3. There was no correlation to the nutritional status or the Shwachman scores. In all patients with CF albumin, TBG and TBPA were also normal. Our results indicate a subclinical hypothyroidism in CF. Routine therapy with thyroid hormones is neither necessary nor recommended.     

Thyroid function in premature infants of different gestational age during the first month of life (author's transl)

To assess the function of the thyroid gland in premature infants of different gestational ages during the first month of life we determined simultaneously TSH, T4, T3, and rT3 serum concentrations in 116 preterm infants (gestational ages 31st to 38th week) during each of the first 30 days of life. The serum concentrations of TSH, T3, and rT3 changed significantly during this period. The TSH and rT3 values were highly increased on the first day and decreased thereafter. The T3 values, however, increased significantly during this period. During the first month of life the T4 values remained roughly unchanged independent of the age of the children. There was no significant influence on serum concentrations of thyroid hormones by gestational age. The 65 preterm infants with adaptational disorders showed no difference in their patterns of TSH and thyroid gland activity during the first month of life compared with 51 healthy premature infants. From the 4th to the 6h day of life -- a recommended period for the screening of congenital hypothyroidism -- the differences of TSH values measured were insignificant (16-18 muU/ml). The T4 values on these days remained all above 6.8 microgram/dl.     

Thyroid function in children with cystic fibrosis

Serum concentrations of T4, T3, reverse T3 (rT3), TSH, Thyroxine binding globulin (TBG) and Thyroxine binding prealbumin (TBPA) were measured and a TRH-stimulation test was performed in 10 iodide untreated children affected by cystic fibrosis (CF) and in 84 controls.As compared to the controls, CF patients had lower T4 and rT3, similar T3 and TBG and increased T3:T4 ratios. They also had lower TBPA, but this could not account for the low T4. Finally they had higher basal and TRH-stimulated TSH. Our results indicate subclinical hypothyroidism in CF. The mechanisms responsible for this situation are not elucidated by our data.Presented in part at the 41st Meeting of the Italian Society of Pediatrics, October, 22–25, 1981, Bologna, Italy     

Thyroid function in fetus and mother during the second half of normal pregnancy

Thyroid hormones, thyroxine-binding globulin (TBG) and thryrotropin (TSH) concentrations were measured in 46 paired fetal and maternal blood samples collected between 17 and 36 weeks of gestation. The samples were selected retrospectively from fetuses that had undergone cordocentesis for prenatal diagnosis, had been found to be unaffected and confirmed healthy at birth. In maternal serum, total thyroxine (TT4) and triiodothyronine (TT3) concentrations were high, but free thyroxine (FT4) and free triiodothyronine (FT3) were within normal adult ranges; reverse T3 (RT3) increased and TSH levels decreased towards term. Fetal TT4, FT4, TT3, FT3, TBG and TSH levels significantly increased whereas RT3 sharply decreased with gestational age. The ratio of fetal TSH/FT4 significantly decreased, suggesting that the set point for negative feedback of pituitary TSH secretion is changing while the sensitivity of the thyroid gland to TSH increases throughout gestation. There was no significant correlation between the maternal and fetal TBG, TSH, TT4 and FT4, whereas maternal TT3 was positively correlated with fetal TT4, FT4, TT3 and FT3. Normal reference values for maternal and fetal iodothyronines, TBG and TSH throughout the second half of gestation provide insight into fetal thyroid development and may be useful for prenatal diagnosis.     

COMPARISONS BETWEEN SERUM CONCENTRATIONS OF THYROXINE AND THYROXINE-BINDING PROTEINS IN SAMPLES SIMULTANEOUSLY OBTAINED FROM CAPILLARY, PERIPHERAL VEIN, CENTRAL VEIN AND AORTA IN NEWBORN INFANTS

Abstract. Jacobsen, B. B. and Peitersen, B. (University Clinic of Paediatrics, Children's Hospital, Fuglebakken, Copenhagen, Denmark). Comparisons between serum concentrations of thyroxine and thyroxine-binding proteins in samples simultaneously obtained from capillary, peripheral vein, central vein and aorta in newborn infants. Acta Paediatr Scand, 68: 43, 1979.—A total number of 40 newborn infants with various maturity were studied: 13 babies without perinatal events, 19 infants recovered from transient diseases, 6 infants with idiopathic respiratory distress syndrome and 2 infants with asphyxia indicating artificial ventilation. Comparisons were performed between serum concentrations of thyroxine (T₄), thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin (Alb) in capillary versus peripheral vein, aorta versus central vein and, finally, in peripheral versus central veins. In healthy infants serum T₄ concentrations in capillary blood and peripheral vein did not differ significantly. Although serum concentrations of thyroid hormone-binding proteins tended to be increased in aortic compared to central venous specimens no statistically significant differences appeared. In infants in good clinical conditions serum T₄, TBG, TBPA, and Alb levels were 6–8% higher in peripheral than in central veins, possibly primarily due to a hemo-concentrating effect of venous stasis. Therefore, in evaluation of the thyroid variables in newborn infants the technique of blood sampling must be considered. In most infants with idiopathic respiratory distress syndrome and in one asphyxiated baby a remarkable tendency to a low serum TBG and T₄ concentration in peripheral compared to central vein samples, were observed.