Pituitary-thyroid responsiveness to thyrotropin-releasing hormone in preterm and small-for-gestational age newborns.

A dose of 40 microgram 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 that 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.     

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.     

THYROTROPIN RESPONSE TO THYROTROPIN-RELEASING HORMONE IN FULLTERM, EUTHYROID AND HYPOTHYROID NEWBORNS

Abstract. The serum concentration of thyrotropin (TSH) and the TSH response following thyrotropin-releasing hormone (TRH) were studied in 16 euthyroid babies from 16 to 172 hours after birth and in 2 primary hypothyroid babies, 3 and 28 days of age. Serum-TSH was measured before an intravenous injection of 40 μug TRH and after 30 and 180 min. In the euthyroid babies increased basal levels of TSH were seen shortly after birth, followed by a pronounced decline. The extent of TSH increase after TRH could be correlated with the basal levels, and the relative increase was comparable to that which occurs in adults. In the hypothyroid babies very high basal levels of serum-TSH were seen, 125 and 400 μ/ml respectively, with no further increase following TRH stimulation. It was concluded that in euthyroid fullterm newborn, the relative response of serum-TSH to TRH was equal to that of adults, in spite of elevated thyroid hormone concentrations. In the hypothyroid newborn very high levels of serum-TSH were seen and a supplementary TRH-test seems without diagnostic value in congenital hypothyroidism.     

EFFECT OF LONG-TERM GH ADMINISTRATION ON PITUITARY-THYROID FUNCTION IN IDIOPATHIC HYPOPITUITARISM

Abstract. Twenty-four euthyroid children with idiopathic pituitary dwarfism were studied. The euthyroid state for seven of these patients was determined by negative physical examinations, normal plasma T₄ assays and normal ¹³¹I uptakes. For the other children, thyroid function was evaluated with T₃ and T₄assays and on the basis of the TRH test. Each of the children was treated with HGH in one of three different ways. The first group (five cases) was given a HGH dose, ranging from 12.4 to 17.2 IU/m²/week. The second and third groups (nine and ten cases, respectively) were treated with 10 and 20 IU/m²/week, respectively. Treatment was carried out for periods ranging from 6 months to 6 years. After no less than 6 months of treatment, and at intervals of 6 months (or some multiple of 6 months) plasma T₃ and T₄ assays, as well as a TRH test were performed in each patient. In some patients one of the indices was once beyond the upper or lower limit of the normal range (none of the children presented simultaneous abnormal levels of more than one index during the controls). This value, however, returned to within normal limits at the following control. There was no correlation between T₃, T₄ and TSH with the duration of HGH therapy. There was no significant difference between the groups of children treated with the different HGH doses. These data seem to demonstrate that the risk of inducing an alteration in thyroid function in hypopituitary patients during HGH treatment is very slight, and that the irregularly abnormal thyroid indices observed in some of the children during one of the controls might be an expression of their metabolic status at that moment.     

Subclinical Thyroid Hormone Abnormalities in Type I Diabetic Children and Adolescents. Relationship to Metabolic Control

ABSTRACT. The serum levels of thyroid hormones and thyroid stimulating hormone were compared in 64 type I diabetic children and adolescents without ketosis and in 28 age matched normal subjects. Only T₃ levels were significantly different in the diabetic patients (2.38±0.41 nmol/1) than in controls (2.64±0.52 nmol/1) (p<0.01) confirming the existence of the'low T₃ syndrome'in diabetic children. A negative correlation was found between T₃ and blood glucose as well as glycosylated haemoglobin suggesting that short-term hyperglycaemia could regulate T₃ concentration. Thyroid function was not different in diabetic children with or without thyroid antibodies. We conclude that serum T₃, level is influenced by the degree of metabolic control and that thyroid function in diabetic children should be assessed by the measurement of the serum concentration of T₄, FT₄ and TSH.     

Syndrome of Generalized (Peripheral Tissue and Pituitary) Resistance to Thyroid Hormone

Generalized resistance to thyroid hormone (GRTH), or Refetoff syndrome, is a disease in which peripheral tissues show resistance to thyroid hormone. Three patients with this disease were investigated. Cases 1 and 2 involved identical 7-year-old female twins and case 3, a 5-year-old girl. All three patients had goiters, and cases 1 and 2 had sensorineural deafness. In all three, the blood levels of T₄, free T₄, and T₃ were high, while the blood levels of TSH were normal or slightly elevated. The responses shown by blood levels of the thyroid hormone and TSH to administration of propylthiouracil and T₃ suggest that the regulating mechanism in the hypothalamic-pituitary-thyroid system was functional. Upon administration of T₃, no sign of hyperthyroidism was observed.     

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.     

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.     

High and low dose initial thyroxine therapy for congenital hypothyroidism

Objective : To assess factors influencing thyroxine (T₄ levels 1 month after initiating replacement therapy for congenital primary hypothyroidism.
Methodology : A retrospective review of 41 children with congenital hypothyroidism who received either high or low dose initial T₄ therapy. Thyroid scintiscan was performed, and T₄ levels determined before starting treatment and after 1 month.
Results : T₄ levels at 1 month were correlated ( r ²=0.38, P <0.001) with the pretreatment T₄ level ( r = 0.48), as well as with the T₄ dose ( r = 0.46). Suboptimal treated T₄ levels (<130nmol/L) were seen with greater frequency in infants with thyroid agenesis (7/11) rather than ectopia (7/28, P <0.03), despite receiving similar doses of thyroxine. Infants with suboptimal treated T₄ levels had lower pretreatment T₄ levels than those with optimal levels (21±7 vs 48±34nmol/L, P <0.02). Biochemical hyperthyroidism (T₄ >216nmol/L) occurred in six patients: four of six had ectopia.
Conclusions : These data suggest that infants with little residual thyroid function should receive higher initial T₄ doses than those with significant ectopia.     

Serum lecithin: cholesterol acyltransferase activity and HDL2 and HDL3 composition in small for gestational age newborns

The aim of this study was to determine serum lecithin: cholesterol acyltransferase (LCAT) activity in parallel with HDL₂ and HDL₃ composition in cord sera of small for gestational age (SGA) newborns, and to compare them with those obtained from appropriate for gestational age (AGA) newborns. LCAT activity was assayed by conversion of [³H]cholesterol to labelled cholesteryl ester. HDL₂ and HDL₃ were separated by ultracentrifugation. Serum cholesteryl ester, apolipoprotein (apo) A-I concentrations and LCAT activity were significantly lower (-47%, -18% and -56%, respectively), whereas serum triglyceride amounts were twofold higher in SGA newborns than in AGA newborns. In SGA newborns, HDL₂ and HDL₃ levels were low, and HDL₃ and HDL₂ phospholipid and HDL₂-cholesteryl ester contents were diminished. HDL₃-apo A-I, A-fl, C-III and E values were lower in SGA newborns. In HDL₂, apo A-I, A-II and E concentrations were decreased. Therefore, in SGA newborns, the reduced LCAT activity was associated with quantitative and qualitative changes in HDL₂ and HDL₃ particles.     

Subclinical hypothyroidism in in vitro fertilization babies

Aim: Assisted reproduction technology is used widely all over the world. There is a great concern about the morbidity of in vitro fertilization (IVF) babies, but investigations are mostly related to mechanical conditions that are attributed to multiparity. This paper aimed to investigate the effect of IVF on thyroid functions in newborns. Methods: A total of 98 healthy, term IVF newborns were evaluated between postnatal 2–4 weeks of age by screening of thyroid functions between July 2006 and April 2008. Ten subjects were assessed as a study group whose thyroid‐stimulating hormone (TSH) levels were higher than 6.5 mU/L. Control group consisted of randomly selected 10 naturally conceived infants with hyperthyrotropinemia (whose TSH levels were higher than 6.5 mU/L but under 15 mU/L) with the same age. All children were thoroughly examined, and serum fT4, TSH, anti‐thyroid peroxidase and anti‐thyroglobulin antibodies were measured, and a thyrotropin‐releasing hormone (TRH) test was performed in all subjects in both groups. Results: Euthyroid hyperthyrotropinemia was diagnosed in approximately 10% of IVF babies. Exaggerated TSH levels to TRH were obtained in all IVF babies (subclinical hypothyroidism) but in none of the controls. A significant difference was noted in the concentration of TSH at the 20th min between the two groups (p < 0.001). Besides, sustained and delayed TSH responses were observed in IVF babies. Neonatal screening tests were negative in both of the groups. Conclusion: In IVF babies, despite normal neonatal screening tests, subclinical hypothyroidism might be observed that suggests the need for screening in this respect.     

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.     

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 Children's 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.     

EFFECT OF CYPROTERONE ACETATE (CA) ON GROWTH AND ENDOCRINE FUNCTION IN PRECOCIOUS PUBERTY

Abstract. Stahnke, N., Ilicki, A. and Willig, R. P. (Department of Paediatrics, University Hospital, Hamburg, West Germany). Effect of cyproterone acetate (CA) on growth and endocrine function in precocious puberty. Acta Paediatr Scand, Suppl. 277: 32, 1979.–16 girls with precocious puberty have been studied. Following low dosage cyproterone acetate (CA) therapy (mean daily dosage 65 mg/m² BSA) a beneficial effect on growth and skeletal maturation was observed. During high dosage therapy (150 mg/m² per day) endocrinological studies were performed in 10 of these patients. There was no significant difference in HGH levels (insulin-and arginine-test), T₃ and TSH values (TRH-test) between patients and controls, T₄ concentration was significantly increased. Basal prolactin levels and prolactin response to TRH was definitely elevated. Oral glucose load and arginine infusion resulted in a significantly enhanced insulin release. There was a significant reduction in basal LH levels and an increase in FSH response to LH-RH. Basal and diurnal plasma cortisol values were markedly reduced and the cortisol release due to corticotrophin injection, (lsinevasopressin (LVP) injection and insulin-hypoglycemia as well. A definite increase in basal ACTH levels was observed, during LVP-and insulin-hypoglycemia test ACTH concentrations were within or significantly above normal range. In our patients a primary adrenocortical insufficiency due to CA treatment was evident.     

TRI-IODOTHYRONINE AND THYROXINE IN HUMAN MILK

ABSTRACT. The concentration of tri-iodothyronine (T₃) and thyroxine (T₄) in human milk was determined by radioimmunoassay (RIA). The analysis of T₃ was performed on unextracted milk and on ethanol extracts of defatted milk. Analysis of unextracted milk was complicated by artifacts. Reliable and reproducible results were achieved only with the milk extracts. In 10 colostral milk samples the mean T₃ levels ± SD were 0.80 ± 0.52 nmol/l before feeding (early milk) and 0.93 ± 0.62 after feeding (hind milk). The T₃ concentration in colostrum did not change significantly during the feeding to the infant. In 12 mature milk samples collected between infant feedings, the mean T₃± SD was 1.19 ± 0.42 nmol/l. T₄ was not detected in any of the samples analysed (detection limit 3 nmol/l).     

Thyroid gland volume as measured by ultrasonography in preterm infants

The volume of the thyroid gland was determined by ultrasonography in 30 preterm infants (27-36 weeks' gestation) born in Madrid. Thyroid gland volume significantly increased (p < 0.01) with postnatal and postmenstrual age and was very well correlated with body weight, height and surface area (p < 0.01). Serum thyroid hormones 3,5,3'-triiodothyronine (T₃) and free thyroxine (FT₄) were linearly correlated with postnatal and postmenstrual age, thus T₃ and FT₄ levels were also correlated with thyroid gland volume (p < 0.05). We report measurements of the thyroid gland volume obtained by ultrasonography in this group of preterm infants. Quantitative determination of thyroid gland volume is more accurate for the diagnosis of goitre than clinical criteria. It is also interesting to determine the thyroid gland volume in the neonatal period when the thyroid is particularly hypersensitive to the effects of iodine deficiency and excess.     

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.     

Fetal hypopituitarism: perinatal endocrine and morphological studies in two cases

We report two infants with congenital absence of the anterior pituitary gland, documented by magnetic resonance imaging (MRI) or autopsy. In cord plasma obtained at birth from both infants, prolactin (PRL), pituitary growth hormone (hGH), placental growth hormone (hPGH) and thyrotropin (TSH) were undetectable; cortisol was low; thyroxine (T₄) was 31 nmol/l in one infant and 85 nmol/l in the other infant who had been treated prenatally with intra-amniotic L-T₄ administration. In maternal plasma at birth, PRL, hPGH and T₄ were normal and hGH was undetectable. These observations suggest that plasma hGH and PRL in the fetus are exclusively of fetal pituitary origin, hPGH is secreted into the maternal circulation and is not transferred to the fetus and fetal growth can be normal in the absence of hGH, hPGH and PRL in fetal plasma.     

PLACENTAL TRANSFER OF MATERNAL ANTI-RABBIT IgG CAUSING FALSELY ELEVATED TSH LEVELS IN NEONATES

Abstract. Larsson, A., Hedenborg, G. and Carlström, A. (Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, and the PKU Section, Department of Bacteriology, National Bacteriological Laboratory, Stockholm, and the Department of Clinical Chemistry, Karolinska Institute, Danderyd's Hospital, Danderyd, Sweden). Placental transfer of maternal anti-rabbit IgG causing falsely elevated TSH levels in neonates. Acta Paediatr Scand, 70:699,.–Two infants were found to have markedly increased TSH levels, 104 and 154 mU/l of plasma, respectively, in a routine screening programme for congenital hypothyroidism. The recall limit used was 50 mU/l of plasma. On follow-up, both infants were clinically euthyroid and had normal serum T₄ and T₃. The elevated TSH levels were confirmed only with some commercial radioimmunoassay kits–but not with others. Similar results were obtained in TSH assays of samples from their mothers, who had no other biochemical or clinical evidence of thyroid dysfunction. Both mothers had intense contact with rabbits over long periods. The apparent TSH activity was found to be associated with the IgG fraction. It was neutralized by the addition of normal rabbit serum to the samples and was caused by antibodies to rabbit immunoglobulin. The activity was eliminated from the circulation of both infants with a half-life of approximately one month. Apparently, the heterophilic antibodies were of maternal origin and were transferred to the foetus via the placenta. Infants with so-called transient hyperthyrotropinaemia identified in screening programmes have to be reevaluated to exclude false TSH elevations of this type.     

Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibiting immunoglobulin

Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibitor immunoglobulin (TBII), a thyroid-stimulating hormone (TSH)-receptor blocking antibody, is described in three male siblings born to a mother with autoimmune thyroiditis. These cases are believed to be the first described in Australia. The first child was found to have a serum TSH of 565 mU/L and had a negative thyroid scan when presented for neonatal screening. He was treated with thyroxine but became thyrotoxic at 3 months of age when he was on a dosage of 85 μg/m² of body surface area. He was euthyroid 6 months after discontinuation of therapy. Nine years later a second hypothyroid sibling was born, with a serum TSH of 709 mU/L on day 4. Both mother and child were demonstrated to be strongly positive for TBIl. Again this child was able to cease therapy by the age of 9 months. A third sibling, also TBIl positive, was born 12 months after the second. His TSH was 90 mU/L and his serum thyroxine (T₄) was 169 nmol/L. On this occasion, thyroid stimulation-blocking antibody was found to be present in the serum of both mother and child. Thyroxine therapy was ceased at 1 month. The family present a picture of varying degrees of transient neonatal hypothyroidism due to the transplacental passage of a maternal receptor blocking antibody. The condition is self-limiting, resolving when the immunoglobuiin is cleared from the infant's circulation.