B. Brock Jacobsen

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.

PITUITARY‐THYROID RESPONSIVENESS TO THYROTROPIN‐RELEASING HORMONE IN PRETERM AND SMALL‐FOR‐GESTATIONAL AGE NEWBORNS

Abstract. A dose of 40 μg TRH was injected intravenously in 12 preterm (PT) and 15 small‐for‐gestational age (SGA) babies (with advanced gestational ages) between 5 and 167 hours after birth. Serum‐thyrotropin (TSH) was measured prior to and 30 and 180 min after TRH; serum‐thyroxine (T4) and serum‐triiodothyronine (T3) were measured prior to and 180 min after TRH. The percentage increase in serum‐TSH in PT and SGA babies was comparable to that of fullterm newborns. The serum‐TSH 30 min after TRH in SGA newborns was significantly correlated to basal TSH values, such a correlation could not be shown in the preterms. One SGA and four PT babies had a repeat TRH‐test performed later in infancy: In all but one PT with a gestational age of 27 weeks the TSH rise was lower than in the neonatal period. The thyroid hormone responses after TRH were similar in the two groups of babies. The percentage increase above basal levels were: Median serum‐T3 increase about 46% and median serum‐T4 increase about 14%. It is concluded that in low‐birth‐weight newborn babies the pituitary TSH response to exogenous TRH was like that detected in fullterm newborns and more pronounced than later in infancy. The effect of endogenous TSH as measured by thyroid hormone increases was of the same magnitude as observed in fullterms and in adults.

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, Childrens 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.

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.

X-LINKED CONGENITAL ADRENAL HYPOPLASIA A Study of Five Generations of a Greenlandic Family

ABSTRACT. In a Greenlandic family comprising 171 descendants in 5 generations, 11 boys had died with a clinical picture of adrenocortical insufficiency within three weeks of birth. Three treated male patients, who survived, were closely studied. The adrenal glands could not be identified by computed tomography. The clinical picture and biochemical studies were consistent with congenital adrenal hypoplasia. The pedigree indicates X‐linked recessive inheritance. The pubertal development was delayed in two patients aged 14 years. LHRH stimulation yielded a significant rise in LH and FSH in at least one of the patients, adrenal androgen values were very low. A family instruction programme has been set up.

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 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 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.

COMBINED TEST OF HYPOTHALAMIC‐PITUITARY FUNCTION IN GROWTH RETARDED CHILDREN TREATED WITH GROWTH HORMONE I. Secretion of Growth Hormone and Somatomedin before and after Treatment

Abstract. Kastrup, K. W., Andersen, H., Eskildsen, P. C., Jacobsen, B. B., Krabbe, S. and Petersen, K. E. (Childrens Hospital, Fuglebakken and Herlev Hospital, Copenhagen, Denmark). Combined test of hypothalamic—pituitary function in growth retarded children treated with growth hormone. Acta Paediatr Scand, Suppl 277: 9, 1979.—In 23 growth retarded children two consecutive insulin tolerance tests (ITT) were performed to establish a diagnosis of growth hormone (GH) deficiency. Nine children did not respond (GH peak value less than 8 mU/l), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/l). All were treated for an average period of 40 months with human growth hormone (HGH). In a combined stimulation test at the end of the treatment period 9 children demonstrated a persistent GH deficiency, whereas a normal response was found in 14 of the previous partial GH deficient children. During treatment the monthly growth rate rose from 0.21 cm to 0.58 cm in the GH deficient children and from 0.31 cm to 0.70 cm in the partial deficient children, in most of whom spontaneous pubertal development occurred during treatment. Somatomedin (SM) values were decreased in the GH deficient children before and after treatment but increased to normal levels during treatment. Growth velocity in these children during treatment was correlated to SM values before treatment. In the partial GH deficient children SM values were subnormal before but normal after treatment. This supports the assumption that in some children with constitutional delay in puberty a reversible functional hypopituitarism exists, which is normalized after the onset of puberty, due to androgens sensitizing growth hormone releasing mechanisms. Treatment with HGH may induce increased growth velocity in some of these patients.

COMBINED TEST OF HYPOTHALAMIC-PITUITARY FUNCTION IN GROWTH-RETARDED CHILDREN TREATED WITH GROWTH HORMONE: II. Secretion of LH, FSH, TSH, Prolactin and ACTH

Abstract. P. C. Eskildsen, B. B. Jacobsen, K. W. Kastrup, S. Krabbe, P. E. Lebech and K. E. Petersen (The Childrens Hospital Fuglebakken, Herlev Hospital and Frederiksberg Hospital, Copenhagen, Denmark). Combined test of hypothalamic‐pituitary function in growth‐retarded children treated with growth hormone. Acta Paediatr Scand, Suppl. 277: 14, 1979.—A total number of 23 patients treated with human growth hormone were retested by use of a combined pituitary stimulation test. Plasma concentrations of GH, FSH, LH, TSH, T4, T3, prolactin (PRL), ACTH and cortisol were measured before and after stimulation with hypoglycemia, TRH and LHRH. The test was performed in patients with persistent GH deficiency (group A) and patients with transitory GH deficiency (group B). In group A a normal pubertal development was found in three patients, whereas in prepubertal subjects the FSH/LH responses were smaller than those of prepubertal patients in group B. Also plasma ACTH increase was less pronounced in group A patients than in group B. In contrast, the plasma TSH and PRL responses were more sustained in group A than in group B. The secretory pattern of TSH and PRL was comparable in the two groups of patients. Thus, in patients with persistent GH deficiency additional multiple disturbances of the hypothalamic‐pituitary function often appeared whereas in most patients with transitory GH deficiency the combined pituitary test was normal at the reinvestigation.

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, Childrens 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.

Congenital primary hypothyroidism and HLA.

ABSTRACT. Previous studies have suggested an association between congenital hypothyroidism and HLA‐Aw24 or B18 antigens. The frequencies of HLA‐A, B and C antigens were studied in 33 unrelated Danish patients with congenital hypothyroidism (5 with aplasia of the thyroid gland, 16 with ectopic thyroids and 8 with thyroid hyshormonogenesis). HLA‐Aw24 only appeared in patients with ectopic thyroids and HLA‐B18 was only seen in patients with dyshormonogenesis. However, the frequencies of HLA antigens in patients and in a large number of controls did not differ statistilly significantly. We conclude that HLA typing is without any predictive value in determining the risk of developing or giving birth to a child with congenital hypothyroidism.