Transient secondary hypothyroidism and thyroxine binding globulin deficiency in leukemic children during polychemotherapy: An effect of L-asparaginase

Recently it has been observed that L-asparaginase causes transient thyroxine binding globulin (TBG) deficiency in adults. In the present study we investigated the influence of L-asparaginase on the pituitary-thyroid axis and on the synthesis of TBG. 14 children with acute lymphoblastic leukemia were treated with a combination of L-asparaginase, vincristine, prednisone and daunomycin for remission induction. Thyroid function was monitored by measuring total T₄, free T₄, total T₃, TSH and TBG with specific radioimmunoassays before, during and after treatment. Within 3 weeks of L-asparaginase therapy total T₄ fell significantly from 10.7±1.6 to 2.9±1.8 g/100 ml, free T₄ from 1.77±0.4 to 0.94±0.35 ng/100 ml, total T₃ from 0.99±0.23 to 0.35±0.2 ng/ml and TBG from 29.4±3.6 to 8.0±3.8 g/ml. Basal TSH values tinuation of L-asparaginase, but following further treatment with other antileukemic agents, all values became normal within 2–4 weeks. In 6 patients with hypothyroid free T₄ values TRH induced TSH release was totally blocked during L-asparaginase therapy. Our data clearly demonstrated that L-asparaginase caused a transient TBG deficiency. Total T₄ and T₃ were in the hypothyroid range because of low TBG concentrations. In addition to TBG deficiency transient, secondary hypothyroidism occurred in approximately 40–50% of all patients treated with L-asparaginase. These alterations were most likely caused by drug induced inhibition of protein synthesis. Under certain circumstances thyroid hormone replacement might be life-saving in severely ill patients suffering from transient, drug induced hypothyroidism.Presented in part at the 19th Meeting of the European Society for Pediatric Endocrinology, August 31–September 3, 1980, Bergamo/Italy     

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.     

Changes in thyroid function tests induced by 2 month carbamazepine treatment in l-thyroxine-substituted hypothyroid children

In five l-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T₄) and free T₄ (FT₄) significantly (P<0.01) decreased following 2 months of carbamazepine (CBZ) administration (20 mg/kg per BW per day) from mean (±SD) values of 12.7±1.1 g/dl and 15.5±1.8 pg/ml to mean values of 7.5±2.3 and 10.1±1.7, respectively. In all but one patient important changes in both serum total and free triiodothyronine (T₃, FT₃) were not observed; consequently T₃T₄ and FT₃FT₄ ratios significantly (P<0.05) increased in the whole series. Three subjects had post-treatment serum TSH that rose to hypothyroid levels parallel to a T₄ decrease. The negligible thyroid hormone secretion and the unmodified T₃-uptake (T₃U) or T₄-binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings observed, instead, might be due to accelerated T₄ metabolic clearance together with augmented T₄ to T₃ conversion rate, as previously demonstrated for diphenylydantoin. The sharp reduction in T₄ and FT₃ concentrations is the peripheral display of this event, which is associated with a decompensation of the metabolic status, as indicated by serum TSH enhancement. In all cases a supplement of l-thyroxine by itself was able to restore euthyroid TSH serum concentrations, suggesting that hypothyroidism in patients with partial epilepsy to whom CBZ had been administered requires a higher l-T₄ substitutive regimen.Abbreviations CBZ carbamazepine - DPH phentoin - T₄ thyroxine - T₃ triiodothyronine - TSH thyrotropin - FT₄ free T₄ - FT₃ free T₃ - rT₃ reverse T₃ - TBG thyroxine binding globulin - T₃U T₃ uptake - RIA radioimmunoassay Presented in part at the 23rd Annual Meeting of the European Society for Pediatric Endocrinology (Heidelberg, September 2–5, 1984) [5]     

Circulating thyroid antibodies and thyroid function studies in children and adolescents with insulin-dependent diabetes mellitus

Significant high titres (1400–125,600) of circulating thoroid microsomal antibodies (MCHA) were found in the sera of 5 out of 59 non-ketoacidotic, insulin-dependent diabetic (IDDM) patients (mean age 14.5 years). Among these five patients (four females, one male), all of whom were over 11 years, two also had thyroglobulin antibodies. Increased thyrotropin (TSH) response to TRH was found in 3/5 MCHA positive patients and in 3/54 without circulating MCHA. Serum thyroxine (T₄) and free T₄ (FT₄) average values were significantly lower (P<0.01 and P<0.001) in diabetics (7.1±1.8g/dl and 10.2±3.1 pg/ml, x±SD) as compared to normal sex and age matched controls (8.9±1.9 g/dl and 12.2±2.2 pg/ml, respectively). T₄ and FT₄ values were inversely related to the duration of the disease. Subnormal T₄ values were found in six (five females and one male) patients, four of whom had subnormal FT₄ values. No patient had low triiodothyronine (T₃) and high reverse T₃ (rT₃) values, i.e. none displayed the biochemical pattern of the low T₃ syndrome described with ketoacidotic status. This indicates also a satisfactory compensation of IDDM in all the patients. At the time of study no patient (including also those with circulating MCHA and TGHA and with TSH hyper-response to TRH) showed either thyroid size enlargement or clinical features of thyroid dysfunction including impaired growth and bone age retardation.Abbreviations MCHA thyroid microsomal antibodies - IDDM insulin-dependent diabetes mellitus - TSH thyrotropin - T₄ serum thyroxine - FT₄ free T₄ - T₃ triiodo thyronine - FT₃ free T₃ - rT₃ reverse T₃ - TGHA thyroglobulin antibodies - TRH thyrotrophin releasing hormone     

3,3′,5′-Triiodothyronine (reverse T3) in amniotic fluid and cord serum

3,3,5-triiodothyronine (reverse T₃, rT₃) was measured in 122 samples of amniotic fluid obtained between the 29th–40th weeks of gestation, and in the blood of 37 newborn and their mothers. The mean rT₃ concentration in amniotic fluid was 0.769±0.47 ng/ml, with a slight decrease from the 29th–40th weeks of gestation which was not statistically significant. Because of the great scatter of rT₃ concentrations in amniotic fluid, its estimation does not seem to be useful in prenatal diagnosis of hypothyroidism. The mean rT₃ concentration in cord blood (2.62 ng/ml; range 1.4–4.9 ng/ml) was greatly elevated in comparison to the mean maternal level at delivery (0.34 ng/ml; range 0.08–0.69 ng/ml). The possible use of rT₃ measurements in cord blood as a screening test for congenital hypothyroidism is discussed.

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Zusammenfassung 3,3,5-Trijodthyronin (Reverse T₃, rT₃) wurde in 122 Frucht-wasserproben aus der 29.–40. Schwangerschaftswoche und im Blut von 37 Neugeborenen sowie deren Müttern bestimmt. Der mittlere rT₃-Gehalt der Fruchtwasser lag bei 0,769±0,47 ng/ml; ein leichter Abfall der rT₃-Konzentrationen bei steigendem Gestationsalter war statistisch nicht zu sichern. Aufgrund der großen Streuungen scheint das rT₃ zur praenatalen Hypothyreosediagnostik ungeeignet. Die mittlere rT₃-Konzentration im Nabelschnurblut von 2,62 ng/ml war gegenüber dem durchschnittlichen rT₃-Spiegel der Mutter unter der Geburt von 0,34 ng/ml stark erhöht. Die mögliche Verwendung der rT₃-Messung im Nabelschnurblut zum Hypothyreose-Screening wird diskutiert.

     

Thyroid function in healthy normal,low birthweight and preterm infants

To delineate more precisely the role of gestational age, weight at birth and thyroid status at birth on the postnatal changes in thyroid hormone levels, serum T₄, T₃, TSH and in some cases FT3I were measured at birth and at 3–4 h, 24–30 h, 6–9 days and 13–20 days.Subjects studied were healthy appropriate-for-date (AFD) and small-for-date (SFD) term neonates and healthy AFD and SFD preterm children. At birth T₄ and T₃ are related to both gestational age and weight with T₄ and T₃ showing lower values in preterm and SFD term neonates than in AFD term children. After birth T₄ and T₃ concentrations show a better correlation with gestational age than with weight at birth.For TSH no correlation was found at birth, a positive correlation at 24–30 h, no correlation at 6–9 days and a negative correlation at 13–20 days both with gestational age and weight at birth. In term and close-to-term infants (36 weeks) individual T₄ levels at 6–7 days show a colse relationship with those at birth; in the younger children (34 and 35 weeks) lower T₄ values are found, despite equal cord blood values. The individual cord blood FT3I/TSH values correlate well with those at 6–7 days of age.It is concluded that after birth all children have changing T₄ and T₃ values, but the pattern and level are influenced by the maturity of the child and its thyroid status at birth measured by T₄ and by the FT3I/TSH ratio. Weight at birth influences T₄ at birth, but during the 1st week the weight of the child influences the T₄ and T₃ levels in only a minor way.Abbreviations AFD appropriate for date - SFD small for date - CHT congenital hypothyroidism     

Neonatal screening for congenital hypothyroidism in a developing country: problems and strategies

Neonatal screening in India poses more organisational and socio-economic rather than medical challenges. Based on the pilot study of 450 cord sera, the plan for screening considered cord TSH<30 μU/ml as normal, 30 to 80 as borderline with recall by letters and >80 as indicative of hypothyroid state, with recall by home visits. Of the 17,240 live births only 12,407 cord sera were collected. Envisaging follow-up difficulties, T₄ was assayed in cord sera when TSH was>30 μ U/ml. 2·81% (350) babies needed recall. Only 30% of 302 (2·43%) babies with cord TSG 30 to 80 responded, to recall letters and were normal; availability of both cord TSH and T₄ helped in excluding hypothyroidism in majority of non-respondents. Forty-eight (0·38%) newborns had TSH>90 μU/ml; 80% of this group and 100% with TSH> 100 μU/ml were traced by home visits. Hypothyroidism was confirmed in 5/48, biochemically and by thyroid scan. All five hypothyroids had cord TSH>300 μU/ml. The incidence in this nonendemic region of India was 1∶2481. Thus false elevation of cord TSH 30 to 300 μU/ml was noted in 0·34% with a chance of detecting a hypothyroid 1 in 10 when TSH>80 μU/ml. Screening strategies in a developing country must ensure meticulous clerical assistance, co-operation and education of nurses and parents, precise and cost effective technics and facilities for continued surveilance of detected hypothyroids.     

Evaluation of the pituitary-thyroidal axis in newborns undergoing exchange transfusion

To evaluate whether the hypothyroxinaemia, previously noted in hyperbilirubinaemic newborns immediately after exchange transfusion for Rh or AB0 incompatibility, was due to impairment in the secretion of thyroid stimulating hormone (TSH) by the pituitary, we studied the thyroid hormone response to thyrotropin releasing hormone (TRH) and compared this response to that seen in a control population of healthy neonates. All infants studied responded with a brisk TSH increase; 30 min after TRH injection the mean TSH concentration of the hyperbilirubinaemic patients was 37 U/ml, ten times their basal level, which was not different from the value noted in the control population.No significant change in total thyroxine (T₄), 3,5,3 triiodothyronine (T₃), free thyroxine (FT₄) or 3,3,5 triiodothyronine (rT₃), (FT₄) or (rT₃) was noted after TRH administration in either group of neonates. In addition the effect of exchange transfusion on the thyroid axis of hyperbilirubinaemic newborns was evaluated. Before the exchange transfusion TSH, T₄, rT₃, T₃ and FT₄ levels were higher in the hyperbilirubinaemic newborns than in donor blood; immediately post-exchange transfusion TSH and T₄ concentrations of the hyperbilirubinaemic neonates decreased significantly and remained significantly below pre-exchange values 30h later.Newborns undergoing an exchange transfusion respond appropriately to TRH stimulation and seem to have an intact pituitary-thyroidal axis.Abbreviations T₄ total thyroxine - FT₄ free thyroxine - T₃ (Ru) T₃ resin uptake - T₃ 3,5,3 triiodothyronine - rT₃ 3,3,5triiodothyronine - TSH thyroid stimulating hormone - TRH thyrotropin releasing hormone - RIA radioimmunoassay     

Influence of Mode of Delivery on Fetal Pituitary-Thyroid Axis

We measured the cord serum levels of thyroid-stimulating hormone (TSH), thyroxine (T4) and triiodothyronine (T3) in 922 neonates delivered by mothers who had no thyroid disorders. The T4 and T3 levels increased progressively from the 27th to the 40th week of gestation. However, the TSH levels varied widely and had no correlation with gestational age, because they were affected by the mode of delivery. The mean cord serum TSH level in neonates delivered by vacuum extraction was 16.3 ±10.0 µUml (n = 30), which was significantly higher than the level following normal vaginal delivery (9.5 ± 6.0 µ U/ml, n = 622) (p < 0.005). The mean cord serum TSH level following elective caesarean section was 6.5 ± 3.1 µ U/ml (n = 79), and this was significantly lower than after normal vaginal delivery (p< 0.005). TSH levels in high-risk neonates were significantly higher than in neonates without risk factors. A significant positive correlation was found between the duration of the second stage of labor and the cord serum TSH level (r = 0.45, n = 412, p<0.01). However, there was no correlation between the cord serum TSH level and the congenital hypothyroidism screening TSH level (r = 0.01, n = 468). We conclude that the cord serum TSH level reflects delivery stress and that an elevated level does not influence the congenital hypothyroidism screening TSH test in which blood is obtained at five days of life.     

Thyroid function in fullterm and preterm newborns

The development of the hypothalamic-pituitary-thyroid system in the fetus occurs through three phases: thyroid pituitary embryogenesis, maturation of hypothalamus, maturation of thyroid system, neuroendocrine control and T₄ tissue deiodination. Defects in early phases I and II lead to permanent disorders whereas abnormalities in phase III result in transient functional immaturities especially in preterms. Cord serum TSH, T₄ and T₃ were estimated in 450 newborns (390 full term>36 wk gestation and 60 preterms<36 wk). The mean cord TSH of 5·069±7·4 μ U/ml in full term was lower than 7·88±3·77 μ U/ml in preterms (P<0·01). The mean cord T₄ and T₃ were significantly higher (P<0·01) 9·716±6·44 μg/dl and 0·425±0·17 ng/ml in full term as compared to preterms 6·46±3·4 and 0·355±0·16 respectively. There was significant negative correlation of serum TSH (r=−0·84 and P<0·05) and positive correlation of serum T₄ (r=0·97, P<0·001) and T₃ (r=0·89, P<0·05) with gestational age. The relationship of these hormones to weight irrespective of gestational age was more significant when compared in newborns >3 kg and <2 kg rather than in all intermediate groups. No significant differences in these hormones were evident amongst the AGA and SGA infants above and below 36 weeks gestation. Transient hypothyroxinemia, and hyper-thyrotropinemia, transient primary hypothyroidism and low T₃ syndromes are some of the transient abnormalities of thyroid function and are more commonly encountered in preterms.     

Cord blood thyroid‐stimulating hormone and free T4 levels in Turkish neonates: Is iodine deficiency still a continuing problem?

Background: The objectives of this study were to determine the cord blood thyroid‐stimulating hormone (TSH) and free T₄ (FT₄) levels in Turkish neonates and to determine whether these variables reveal iodine deficiency. Methods: We collected 818 cords from healthy mothers at parturition and measured levels of FT₄ and TSH. We also measured cord blood FT₄ and TSH levels in different stages of gestation and gender. We grouped the neonates according to cord serum TSH levels, either being less (Group A) or greater (Group B) than 10 mIU/L. Group A included 589 neonates (300 girls [51%] and 289 boys [49%]) and Group B included 229 neonates (105 girls [45%] and 124 boys [55%]). Results: The percentage of subjects with cord blood TSH < 10 mIU/L and >10 mIU/L was 72% and 28%, respectively. Although cord TSH levels in Group B were greater than those in Group A (P < 0.001), cord blood FT₄ levels in Group B were lower than those in Group A (P < 0.05). There was no difference between both sex in terms of birthweight and maternal age. TSH and FT₄ levels did not vary according to neonate sex during gestation, except for from week 37 to 41. TSH levels of male neonates at the 41st week of gestation were higher than those of female neonates (P < 0.05). There were no effects of birthweight on TSH and FT₄ levels if the neonate was lighter than 2500 g at birth. TSH levels of male neonates were higher than those of female neonates when their birthweights were <2500 g (P < 0.05). There was no significant difference in TSH levels according to birthweights in male neonates. Conclusion: Our data provide the normative data for cord blood TSH and FT₄ levels in Turkish neonates and show that iodine deficiency is a still a public health problem in Turkey. These measurements can be useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism as well as evaluation of the success of the iodination program.     

Neonatal hypothyroxinemia

Serum thyroxine (T₄) and thyroid stimulating hormone (TSH) were estimated in 25 well term and 30 well preterm neonates in blood samples collected from cord blood and subsequently at 24 hours and 72 hours of age. Cord blood serum T₄ concentration was higher in term than preterm babies. Reverse pattern was observed for serum TSH concentration. Both serum T₄ and TSH showed a rise at 24 hours and a fall at 72 hours of age. None of the neonates had primary hypothyroidism. The incidence of transient hypothyraxinemia in term babies was 4% at birth, nil at 24 hours, and 16% at 72 hours of age. The corresponding values for preterm babies were 63.3%, 3.3% and 23.3%.     

Organisation and implementation of neonatal hypothyroid screening programme in India—a primary health care approach

An objective, sensitive, sophisticated and inexpensive method of estimating thyroxine (T₄) and thyroid stimulating hormone (TSH) has been applied for the neonatal hypothyroid screening programme in India. The cord blood samples were collected at the time of delivery on a No 3 Whatman filter paper strip, and despatched to the central laboratory, in a specially designed pre-paid envelope. The samples were sent by the auxillary nurse midwives and traditional birth attendants, in the framework of existing infrastructure of primary health centres of our country, who also participated in the treatment of detected hypothyroid children.     

Thyroid function in fullterm and preterm newborns

The development of the hypothalamic-pituitary-thyroid system in the fetus occurs through three phases: thyroid pituitary embryogenesis, maturation of hypothalamus, maturation of thyroid system, neuroendocrine control and T₄ tissue deiodination. Defects in early phases I and II lead to permanent disorders whereas abnormalities in phase III result in transient functional immaturities especially in preterms. Cord serum TSH, T₄ and T₃ were estimated in 450 newborns (390 full term>36 wk gestation and 60 preterms<36 wk). The mean cord TSH of 5·069±7·4 μ U/ml in full term was lower than 7·88±3·77 μ U/ml in preterms (P<0·01). The mean cord T₄ and T₃ were significantly higher (P<0·01) 9·716±6·44 μg/dl and 0·425±0·17 ng/ml in full term as compared to preterms 6·46±3·4 and 0·355±0·16 respectively. There was significant negative correlation of serum TSH (r=?0·84 and P<0·05) and positive correlation of serum T₄ (r=0·97, P<0·001) and T₃ (r=0·89, P<0·05) with gestational age. The relationship of these hormones to weight irrespective of gestational age was more significant when compared in newborns >3 kg and <2 kg rather than in all intermediate groups. No significant differences in these hormones were evident amongst the AGA and SGA infants above and below 36 weeks gestation. Transient hypothyroxinemia, and hyper-thyrotropinemia, transient primary hypothyroidism and low T₃ syndromes are some of the transient abnormalities of thyroid function and are more commonly encountered in preterms.     

Effect of perinatal asphyxia on thyroid-stimulating hormone and thyroid hormone levels

AIM: To compare serum concentrations of thyroid hormones--T4, T3, free T4 (FT4) and reverse T3 (rT3)--and thyroid-stimulating hormone (TSH) found in the umbilical cord blood of term newborns with and without asphyxia and those found in their arterial blood collected between 18 and 24 h after birth. A further aim of the study was to assess the association between severity of hypoxic-ischemic encephalopathy and altered thyroid hormone and TSH levels, and between mortality and FT4 levels in the arterial blood of newborns between 18 and 24 h of life. METHODS: A case-control study was carried out. The case group comprised 17 term newborns (Apgar score < or = 3 and < or = 5 at the first and fifth minutes; umbilical cord blood pH < or = 7.15) who required bag and mask ventilation for at least one minute immediately after birth. The control group consisted of 17 normal, term newborns (Apgar score > or = 8 and > or = 9 at the first and fifth minutes; umbilical cord blood pH > or = 7.2). Cord blood and arterial blood samples were collected immediately after birth and 18 to 24 h after birth, respectively, and were used in the blood gas analysis and to determine serum concentrations of T4, T3, FT4, rT3 and TSH by radioimmunoassay. All newborns were followed-up until hospital discharge or death. RESULTS: Gestational age, birthweight, sex, size for gestational age, mode of delivery and skin color (white and non-white) were similar for both groups. No differences were found in mean levels of cord blood TSH, T4, T3 and FT4 between the groups. In the samples collected 18 to 24 h after birth, mean levels of TSH, T4, T3 and FT4 were significantly lower in the asphyxiated group than in the control group. Mean concentrations of arterial TSH, T4 and T3 between 18 and 24 h of life were lower than concentrations found in the cord blood analysis in asphyxiated newborns, but not in controls. In addition, asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy presented significantly lower mean levels of TSH, T4, T3 and FT4 than those of controls. None of the asphyxiated newborns with FT4 > or = 2.0 ng/dl died; 6 out of the 11 asphyxiated newborns with FT4 < 2.0 ng/dl died. CONCLUSIONS: Serum concentrations of TSH, T4, T3 and FT4 are lower in asphyxiated newborns than in normal newborns between 18 and 24 h of life; this suggests central hypothyroidism secondary to asphyxia. Asphyxiated newborns with moderate/severe hypoxic-ischemic encephalopathy present a greater involvement of the thyroid function and consequently a greater risk of death.     

A case of familial thyroxine binding globulin excess associated with growth hormone deficiency

A 7 years 3 months old Japanese boy with familial thyroxine binding globulin (TBG) excess associated with growth hormone (GH) deficiency is reported. The patients height was 106.4 cm (- 2.86 s.d.) and his bone age was 5 years and 3 months. He had no goiter and his developmental milestones were normal. The serum thyroid stimulating hormone (TSH) was 2.8 μU/mL, triiodothyronine (T₃) 3.1 ng/mL, thyroxine (T₄) 23.4 μg/dL and free T₄ 1.8 ng/dL. The serum TBG level was beyond 80.0 μg/mL, with normal TSH response to the thyrotropin-releasing hormone (TRH) test. Familial study revealed that his grandmother, mother, uncle, younger sister and younger brother had high TBG and T₃ levels, thus an X-linked co-dominant transmission was suggested. The peak GH responses to insulin and clonidine hydrochloride were 5.8 and 8.2 ng/mL, respectively. The mean nocturnal GH concentration was 2.5 ng/mL. His growth velocity increased from 4.8 to 8.4 cm/year and his serum TBG levels decreased gradually after human growth hormone (hGH) treatment.     

The effect of intra-partum and intra-uterine asphyxia on placental transfusion in premature and full-term infants

Blood volume and its components were estimated using ¹²⁵iodinated human serum albumin in 194 newborn infants with 26 to 41 week gestations. Umbilical cords were ligated 15 seconds after vaginal delivery (n=141) and within 5 seconds after delivery by Caesarean section (n=53). The infants were divided into four groups according to the mode of delivery and presence of prenatal complications: group I: vaginal deliveries (n=96) and group II: Caesarean section (n=25) without preceding complications; group III: infants with intra-uterine asphyxia (n=56); group IV: infants with tight umbilical cord loops around neck (n=17). Subgroups were established with respect to gestational age and to one-minute Apgar scores. Significantly different blood volume (BV) and red cell mass (RCM) values between the subgroups were only found in group I with respect to different Apgar scores: Ia Apgar>5: BV 77.9±6.2; RCM 37.5±5.1 ml/kg; Ib Apgar<6: BV 70.0±4.4; RCM 29.6±2.9 ml/kg (P<0.005). Intra-partum asphyxia did not affect BV (71.3±4.8 ml/kg) and RCM (31.2±3.6 ml/kg) in group II. BV and RCM were significantly (P<0.005) lower than in group Ia. In group III, BV (90.4±7.0 ml/kg) and RCM (46.9±6.3 ml/kg) were significantly (P<0.005) higher than in group I, irrespective of the mode of delivery and Apgar scores. The infants of group IV had the lowest volumes (BV 67.5±5.7; RCM 27.4±2.7 ml/kg). Values obtained in premature and full-term infants were similar in the respective groups. These results indicate that infants with intra-partum asphyxia and with tight nuchal cords do not participate in placental transfusion or even lose some blood into the placenta. However, infants with intrauterine asphyxia (excepting those with tight nuchal cords) receive marked placental transfusion in utero.Supported by Deutsche Forschungsgemeinschaft, SFB 147     

Treatment of patients with Ullrich-Turner syndrome with conventional doses of growth hormone and the combination with testosterone or oxandrolone: Effect on growth,IGF-I and IGFBP-3 concentrations

Thirty-nine girls with Ullrich-Turner syndrome (UTS) (median age 9.5 years) were treated with growth hormone (GH) with either 12 or 18 IU/m² per week for 12 months followed by combination therapy with either oxandrolone (Ox) (0.0625 mg/kg/day po) or low-dose testosterone (T) (5 mg im every 2 weeks). Growth velocity improved significantly after 12 IU/m² per week (6.4±1.7 cm/year vs 4.0±1.3 cm/year, x±SD,P<0.001) and 18 IU/m² per week of GH (6.5±1.3 cm/year vs 4.5±1.4 cm/year,P<0.001). Ox, but not T was effective in maintaining growth velocity during the 2nd year of therapy (6.9±1.3 vs 5.3±1.5 cm/year). Basal insulin-like growth factor-I (IGF-I) concentrations were in the lower normal range and increased significantly in patients treated with 18 IU/m² per week (357±180 ng/ml vs 160±84 ng/ml) and 12 IU/m² per week (273±121 ng/ml vs 140±77 ng/ml). IGF-I concentrations increased further after addition of Ox (533±124 ng/ml,P<0.001) or T (458±158,P<0.05). IGFBP-3 concentrations were in the upper normal range before therapy and increased only moderately in both GH dosage groups. However, IGF binding protein-3 (IGFBP-3) concentrations were not affected by additional Ox or T treatment.Conclusions 1. Conventional GH doses are effective in increasing growth velocity in UTS, especially, when combined with Ox. This additive effect is not evident when GH is combined with low dose T. 2. Changes in growth velocity are accompanied by an increase of the IGF-I/IGFBP-3 ratio. 3. Ox obviously acts by increasing IGF-I levels independent of the GH status.     

Influence of long-term carbamazepine treatment on thyroid function

We have studied the effects of carbamazepine on thyroid function in sixteen recently diagnosed epileptic children and thirteen epileptic children receiving long-term carbamazepine therapy and compared these findings with the thyroid function of thirteen healthy control subjects. Thyrotropin (TSH), tri-iodothyronine (T₃), thyroxine (T₄), free tri-iodothyorinine (FT₃) and free thyroxine (FT₄) serum levels were determined in both recently diagnosed but as yet untreated epileptic children and normal controls. These hormone levels were determined again after 2 months of treatment and 12 months of treatment in epileptic children. No statistically significant difference was found in the endocrine parameters of untreated epileptic children and the normal control group. After both 2 months and 12 months of carbamazepine therapy, serum levels of T₄, FT₄ and FT₃ were found to be low, but the serum T₃ concentration was unaffected. Baseline TSH levels were not changed during carbamazepine therapy either. Serum TSH levels increased rapidly after thyrotropin-releasing hormone stimulation in both the before and 12 months after carbamazepine treatment groups, but the response was higher in the 12 months treatment group. The findings of the present study suggest that accelerated hormone metabolism is responsible for hormonal changes found in patients treated with carbamazepine. Carbamazepine also had effects on the function of the hypothalamo-pituitary axis.     

Serum thyroxine and triiodothyronine levels in newborns: effect of gestational age

Serum T₄ and T₃ were measured in 31 newborns of gestational ages 32–43 weeks. Out of 31, 11 were term, 12 preterm and 8 postterm. Blood samples were taken from cord blood and from peripheral vein at 24 and 72 hours of age. Serum T₄ and T₃ values were low in cord blood samples, raised in 24 hours samples and then declined in 72 hour samples. In pretern newborns cord T₄ and T₃ values were significantly lower and there was a blunted rise and fall in 24 and 72 hours samples as compared to term newborns. In post term newborns cord serum T₄ and T₃ values were significantly raised while in peripheral vein samples difference was statistically insignificant as compared to term newborns. This high incidence of low cord values and transient hypothyroxinemia observed in preterm and postnatal surge of T₄ may give rise to false results while screening for hypothyroidism.