Effects of anticonvulsant drugs on thyroid hormones in epileptic children.

Serum total and free thyroid hormones, reverse T3 (rT3), thyroxin binding globulin (TBG) and thyroid stimulating hormone (TSH) concentrations were measured in 35 epileptic patients receiving anticonvulsants (phenobarbitone, phenytoin). There was a significant reduction found in total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), free triiodothyronine (FT3) and rT3 in the group treated with, phenytoin. The thyroid hormone levels were within normal limits in the group receiving phenobarbitone.     

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.     

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   

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.     

Familial thyroxin-binding globulin excess with ichthyosis: a case report.

Thyroxin (T4) binding globulin (TBG) the major thyroid hormone transport protein in humans. Congenital or acquired problems lead to TBG excess. Inheritance of TBG excess follows an X-linked pattern. A 21-month-old boy with ichthyosis was referred to the Pediatric Endocrinology Clinic with high levels of thyroid hormones (TT3 = 325 ng/dl, TT4 23 microg/dl, FT3 = 3.49 pg/dl, FT4 = 1.44 ng/dl, TSH = 2.48 microIU/ml). He was clinically euthyroidic. Thyroid gland was normal in size and homogeneous. Thyroid autoantibodies were negative. TSH responded normally to thyroid releasing hormone (TRH) stimulus. TBG was elevated (56 microg/ml). Family investigation revealed high levels of TBG in mother grandfather, and an uncle. To our knowledge, no other TBG excess with ichthyosis has been reported in the literature.     

Thyroid function tests in preterm infants born to preeclamptic mothers with placental insufficiency

OBJECTIVE: Since preeclampsia causes placental insufficiency, it can be hypothesized that it decreases placental passage of thyroxine (T4) from mother to infant and thus may deepen the transient hypothyroxinemia seen in preterm infants after birth. The aim of this study was to compare thyroid function tests of preterm infants born to preeclamptic mothers with placental insufficiency with preterm infants born to mothers without placental insufficiency. METHODS: Thirty-one preterm infants born to preeclamptic mothers with placental insufficiency were included in the study (group I) and 31 preterm infants born to mothers without placental insufficiency were included as the control group (group II). Thyroid hormone levels were assayed from blood samples obtained from the women before birth and thereafter from the infants at delivery (cord) and on the 1st, 3rd, 7th, and 21st days of life. RESULTS: Cord blood triiodothyronine (T3), free T3 (FT3) and free thyroxine (FT4) levels in group I were lower than in group II, whereas thyrotropin (TSH) and thyroxine binding globulin (TBG) levels were higher. No statistical difference in hormone levels studied at postnatal 1st, 3rd, 7th, and 21st day was found between the two groups. CONCLUSION: Low levels of thyroid hormones and high level of TSH in cord blood in premature infants born to preeclamptic mothers with placental insufficiency suggest intrauterine hypothyroidism. Increase in TSH and thyroid hormone concentrations after birth reveal that the hypothalamic-pituitary-thyroid axis is intact.     

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.

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 T4 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 T3 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 less than or equal to 5 mU/l 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.     

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.     

Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone.

We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.     

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。     

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.     

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.     

Reverse triiodothyronine, thyroid hormone, and thyrotrophin concentrations in placental cord blood.

Reverse triiodothyronine (rT3), triiodothyronine (T3), thyroxine (T4), thyroxine binding globulin (TBG), and thyrotrophin (TSH) were measured in sera from placental cord blood in an unselected series of 272 deliveries. In this series the concentrations of rT3 (mean 3.33 nmol/l, 95% confidence limits 1.6--7.0 nmol/l), were log normally distributed and did not overlap the adult normal range (0.11--0.44 nmol/l). There were no correlations between the cord blood concentrations of rT3, T3, T4, and TSH. The cord serum rT3 concentration was not influenced by maturity, birth-weight, or neonatal risk factors, whereas these factors did affect the concentrations of T3, T4, AND TBG. There is no arteriovenous rT3 concentration difference across the placenta, therefore the cord rT3 reflects the systemic rT3 concentration in the baby at birth. As rT3 in the neonate largely, if not entirely, derives from thyroxine from the fetal thyroid, measurement of the cord rT3 concentration may be a good immediate screening test for neonatal hypothyroidism.     

Thyroid hormone levels and their relationship to survival in children with bacterial sepsis and septic shock

OBJECTIVES: Reported studies have showed alternations of thyroid hormones in critical illness mostly in adults and some in children. In this study, we aimed to measure thyroid hormone levels in children with sepsis and septic shock and investigate the relationship of these hormones with clinical state and survival. PATIENTS AND METHODS: Thyroid hormone levels of children with sepsis and septic shock, and age- and sex-matched controls were measured. RESULTS: There were 51 children in sepsis (group S), 21 children in septic shock (group SS) and 30 in the control (group C) group. Total triiodothyronine (TT3) levels were (nmol/l): 0.91 +/- 0.22, 0.64 +/- 0.23, 2.11 +/- 0.59; free triiodothyronine (FT3) (pmol/l): 0.027 +/- 0.006, 0.018 +/- 0.007, 0.049 +/- 0.010; total thyroxine (TT4) (nmol/l): 100.62 +/- 21.93, 65.79 +/- 19.35, 109.65 +/- 19.35; free thyroxine (FT4) (pmol/l): 18.06 +/- 3.87, 10.32 +/- 1.29, 19.35 +/- 3.87; and thyroid stimulating hormone (TSH) (mIU/ml): 5.0 +/- 2.0, 4.8 +/- 2.4, 5.2 +/- 3.0, in children with sepsis, septic shock, and controls, respectively. The TT3, FT3, TT4, and FT4 levels of group SS were significantly lower than those of groups S and C. The TT3 and FT3 levels of group S were lower than in group C, but there was no significant difference between TT4, and FT4 levels of groups S and C. TSH levels were slightly decreased in both sepsis and septic shock, but the difference was not significant. Eleven (21.6%) children with sepsis and 15 (71.4%) children with septic shock died (p < 0.001). The levels of TT3, FT3, TT4 and FT4 were markedly lower in non-survivors of groups S and SS compared to survivors (p < 0.001). CONCLUSIONS: These changes in the hypothalamo-pituitary-thyroidal axis may suggest a possible prognostic value of thyroid hormone levels in children with sepsis and septic shock. To the best of our knowledge, this report is the first study to compare thyroid hormone levels in a large number of patients with sepsis and septic shock with those in healthy controls in childhood.     

Reference values for the concentration of free triiodothyronine (FT3), triiodothyronine (TT3), free thyroxine (FT4), thyroxine (TT4), thyrotropin (TSH) and thyroxine-binding globulin (TBG) in umbilical cord blood. Method: luminescence-enhanced enzyme immunoassay]

Physiological concentrations of FT3, TT3, FT4, TT4, TSH and TBG were determined using the luminescence enhanced enzyme immunoassay method in cord blood serum (n = 100). The results are presented in Table 1.     

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.     

Pediatric thyroid testing issues

Thyroid problems are common in children. While serum thyroid function tests lead to an accurate diagnosis in most patients, unique patient situations can produce misleading results. Total T4 measurements can incorrectly suggest hypothyroidism in congenital thyroid binding globulin (TBG) deficiency and hyperthyroidism in TBG excess, as seen in high estrogen states. Free T4 (FT4) measurement techniques involve either physical separation of unbound thyroxine from serum binding proteins or estimation of FT4 levels in the presence of binding proteins. These estimation techniques are susceptible to under- or over-estimation of FT4 levels when binding proteins are low or high. Other complicating factors arise in the setting of prematurity or systemic non-thyroidal illness (NTI), simulating central hypothyroidism. Thyroid stimulating hormone (TSH) levels in children have a wider normal range than in adults and are affected by drugs and NTI. Additionally, heterophile and anti-T4 or anti-TSH antibodies can interfere with accurate T4 or TSH measurement.     

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.     

Thyroid function and dysfunction in premature infants

During the past four decades major advances in the management of premature infants have led to progressive reduction in mortality. During this period mortality in very low birth weight infants (VLBW, <1500 grams and <30 weeks gestation age) has decreased, and more than 50% of infants less than 24 weeks gestation age now survive, increasing the population of VLBW infants in intensive care nursery environments. Thyroid function in these infants is characterized by decreased TSH and T4 responses to parturition, low serum total T4 and TSH levels and variable free T4 concentrations during the first 2-4 postnatal weeks of life. These features reflect a state of transient hypothalamic-pituitary or central hypothyroidism. There is a high prevalence of morbidity in these infants, as well, often associated with further reductions in serum total T4, T3, TBG and TSH concentrations and variable levels of free T4 and reverse T3, resembling the non-thyroidal illness (NTI) syndrome in adults. The etiologic roles of thyroid system immaturity and NTI in the transient hypothyroxinemia of prematurity (THOP) and the impact of THOP on the subsequent neurological deficits in VLBW infants remains unclear. Several thyroxine supplementation trials have been conducted with inconclusive results. Further studies are planned or in progress.     

Smoking during pregnancy--effects on the fetal thyroid function

Infants delivered at term by mothers smoking at least 10 cigarettes daily during pregnancy (n = 46) were found to be growth retarded compared to infants of non-smoking mothers (n = 49), birthweights 3,445 +/- 385 (SD) g and 3,667 +/- 392 g respectively (p less than 0.05) in the two groups. Cord serum thyrotropin (TSH) was significantly decreased (8.2 +/- 4.0 U/l vs. 10.3 +/- 4.9 U/l) and free thyroxine index (FT4I)/TSH ratio significantly increased (18.8 +/- 9.0 vs. 14.4 +/- 7.6) (p less than 0.05) in the smoking group compared to infants of non-smokers. Cord serum thyroxine (T4) and FT4I were higher in the smoking group (149.0 +/- 22.4 nmol/l and 125.5 +/- 14.9 respectively) compared to infants of non-smoking mothers (140.6 +/- 21.6 nmol/l and 120.0 +/- 16.5 respectively), with borderline statistical significance (0.05 less than p less than 0.10). The results indicate that infants of smoking mothers may have a hyperfunction of the thyroid gland at birth compared to infants of non-smokers, with a negative feed-back on TSH production from the pituitary gland. Increased metabolic rate and oxygen consumption caused by fetal thyroid hyperfunction may be pathogenetic factors for the fetal growth retardation caused by maternal smoking.