SCREENING FOR CONGENITAL HYPOTHYROIDISM

ABSTRACT. Larsson, A., Ljunggren, J. G., Ekman, K., Nilsson, A. and Olin, P. (Departments of Paediatrics and Child Psychiatry, Karolinska Institute, St. Goran's Children's Hospital; the Department of Medicine, St. Göran's Hospital; and the PKU Section of the Department of Bacteriology, National Bacteriological Laboratory, Stockholm, Sweden). Screening for congenital hypothyroidism. I. Laboratory results of a pilot study based on dried blood samples collected for PKU screening. Acta Paediatr Scand, 70:141, 1981. – A pilot study was performed to establish optimal conditions for nation-wide screening for congenital hypothyroidism in Sweden. The levels of T₄ and TSH were determined by automated radioimmunoassay in the dried blood spots, routinely collected for PKU screening on the fifth postnatal day, from all 1979, 2 infants born in the Stockholm area during a 14-month period. To identify safe minimum recall criteria for routine use, infants were recalled if the TSH level was more than 30 mU/l of plasma or–if they were not preterm–the T₄ concentration was less than -2 S.D. of the mean. Altogether 160 infants were recalled. Seven newborns with congenital hypothyroidism were identified, 6 with primary and one with secondary hypothyroidism. Five infants had decreased levels of thyroxine-binding globulin. The results of the follow-up analyses from recalled infants showed that determination of the reverse-T₃ level may be of diagnostic value around the 23rd day of life. The results of the clinical investigation of recalled infants are reported in a subsequent paper and a programme for nation-wide screening for congenital hypothyroidism is proposed.     

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.     

TSH AND THYROXINE IN STORED NEONATAL FILTER-PAPER BLOOD SAMPLES FROM PATIENTS WITH CONGENITAL HYPOTHYROIDISM

ABSTRACT. Filter paper blood samples collected neonatally from infants with congenital hypothyroidism were analysed retrospectively for TSH ( n = 41) and thyroxine ( n = 16). The patients were detected by clinical signs and symptoms and treatment was started during the first two years of life. Similar blood samples from control infants were analysed for comparison. All CH patients would have been detected neonatally if screening had been based on TSH analyses with a cut-off limit corresponding to 50 mU of TSH/I of plasma. A screening programme involving analyses of thyroxine would require considerably higher recall frequency to yield 100% sensitivity. These results support a nationwide CH screening program based on TSH analyses of PKU filter paper blood samples using 50 mU/I of plasma as the cut-off limit.     

CONGENITAL HYPOTHYROIDISM IN SWEDEN Incidence and Age at Diagnosis

ABSTRACT. A total number of 112 children with congenital hypothyroidism were diagnosed in all Children's Hospitals and Pediatric Wards in Sweden during the 7-year period 1969–1975. Since it may be assumed that all cases of congenital hypothyroidism, which were diagnosed during that period were seen in one of these hospitals, the incidence of congenital hypothyroidism in Sweden can be calculated to be 1:6900 live births. In spite of an efficient National Health Care Program for Infants the diagnosis was delayed until after an age of three months in 52% of the cases. This fact supports the view that mass screening of newborns for congenital hypothyroidism has to be introduced in Sweden. However, the beneficial effects of such a program cannot be fully elucidated until it has been considered whether earlier instituted treatment would have improved the outcome of children in whom a diagnosis was made after 3 months of age.     

CONGENITAL HYPOTHYROIDISM IN SWEDEN Psychomotor Development in Patients Detected by Clinical Signs and Symptoms

Abstract. Aim, J., Larsson, A. and Zetterström, R. (Department of Paediatrics, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden). Congenital hypothyroidism in Sweden: Psychomotor development in patients detected by clinical signs and symptoms. Acta Paediatr Scand, 70: 907, 1981. Thirty-nine children at 7 to 9 years of age with congenital hypothyroidism have been studied with respect to their intellectual, neurological and social functions. Their intellectual achievement as assessed by the WISC test, was significantly lower than in a reference population (mean IQ88, range 50–113). In children who showed signs and symptoms of hypothyroidism during their first four weeks of life, there was a negative correlation between the age when therapy was started and intellectual development. No such correlation was found in children who showed signs and symptoms after the first four weeks of life. Nine children of 26 with signs of hypothyroidism in the neonatal period, were found to have neurological abnormalities consisting of fine and gross motor disturbances. The neurological abnormalities seriously affected daily life in only the two most severely mentally retarded. No correlation was found between the age when the therapy was started and neurological abnormalities. Three children attended special schools because of mental retardation and six attended normal schools but required additional teaching assistance for learning disabilities. Our results suggest that the risk of future intellectual handicaps may be reduced by early treatment in children with hypothyroidism presenting during the neonatal period.     

TRANSIENT CONGENITAL HYPOTHYROIDISM IN AN INFANT WITH CONGENITAL NEPHROSIS OF FINNISH TYPE

ABSTRACT. Congenital hypothyroidism was detected on routine neonatal screening in an infant with congenital nephrosis of Finnish type and followed up for 3 years. The hypothyroidism was transient; clinical and biochemical signs and symptoms disappeared after a 20-month period of thyroid replacement therapy and partial improvement of nephrotic symptoms.     

GROWTH AND DEVELOPMENT IN A GIRL WITH PSEUDOHYPOPARATHYROIDISM AND HYPOTHYROIDISM

ABSTRACT. Statural growth, physical and skeletal development of a girl with pseudohypoparathyroidism and primary hypothyroidism were analysed in a longitudinal study, which lasted for 12 years from the age of 0.8 years. Growth in height, which slowed down when thyroid therapy was withheld, was within the normal range. Still, as a result of early puberty, the girl became a small adult. Skeletal age was advanced over chronological years by an average of 2.7 years. This rapid skeletal development was more pronounced in the tubular bones than in the round bones of the hand. Two of the five metacarpals of the left hand grew more slowly than the others. This became clinically apparent at the age of 5.6 years. In all five metacarpals growth ceased at the same time, indicating that the abnormally short size of the two metacarpals did not result from early epiphyseal closure.     

CEREBELLAR-ATAXIC SYNDROME IN CHILDREN AND ADOLESCENTS WITH HYPOTHYROIDISM UNDER TREATMENT

ABSTRACT. Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7–24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20 %) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospecitvely, these data might permit a more accurate prognosis of further mental development in hypothyroid children.     

Congenital Hypothyroidism

Availability of sensitive radioimunoassays for T₄ and TSH has simplified the detection and treatment of congenital hypothyroidism. Early diagnosis by newborn screening and prompt treatment should minimize the serious complications of mental retardation. Absence of clear cut signs and symptoms early in the life requires laboratory testing for early diagnosis. The high cost effectiveness of the screening programme has resulted in the implementation of mass screening in many countries. Several studies indicate a favourable IQ with initiation of treatment before the age of 3 months. Neonatal laboratory screening programs have made it possible to initiate treatment before one month of age. This may further improve the outcome of this common cause of preventable mental retardation.     

CONGENITAL HEART DISEASE AND ITS ASSOCIATION WITH OTHER CONGENITAL MALFORMATIONS FOUND AT AUTOPSY

The objective was to determine if a study of other malformations found at autopsy in patients with congenital heart disease would contribute to an understanding of the mechanisms involved in the formation of these anomalies. In a large general hospital autopsies in children with congenital heart disease were selected, and the different cardiopathies were divided into 3 groups: those with isolated heart lesions, those with single gene mutants, as well as chromosome malformations, and those with idiopathic malformations not associated with a genetic syndrome. Because the cardiopathies most often associated with genetic syndromes were the septal defects in general (p = .001), it was presumed that these are influenced to a considerable extent by genetic factors. The association of left heart hypoplasia and coarctation of the aorta with multiple idiopathic malformations, particularly in the lower half of the body (p = .002), suggests that the latter may be due to vascular disruptions, because of the interruption of the flow of oxygenated blood in the embryo-fetus produced by these heart defects. Cranial defects were not associated with left heart obstruction, and are therefore unlikely to be produced by vascular disruption.     

Neonatal screening for congenital hypothyroidism in the Federation of Bosnia and Herzegovina: eight years’ experience

This report demonstrates the prevalence of primary congenital hypothyroidism (CH) in the Federation of Bosnia and Herzegovina and summarizes the laboratory data. Neonatal thyroid-stimulating hormone (TSH) was measured in whole blood drawn between the 3rd and 5th days of life and spotted on filter paper using the fluorometric assay. Among the 87,061 neonates, 22 had CH, 13 dysgenetic forms, and nine with thyroids in situ. No differences were found between the two types in terms of TSH and total T4 concentrations. However, thyroglobulin was significantly lower in patients with dysgenetic thyroid tissue (p = 0.0023). We conclude that the prevalence of CH in the Federation of Bosnia and Herzegovina is 1:3,957 newborns.     

CONGENITAL HYPOTHYROIDISM AND CHANGES IN THE ENAMEL OF DECIDUOUS TEETH

ABSTRACT. Deciduous teeth from children with congenital hypothyroidism were collected and ground sections were prepared. The sections were analysed by means of polarised light and microradiography. The enamel in ground sections of deciduous teeth from children with congenital hypothyroidism showed an increase in areas with elevated pore volume distribution in both the pre- and postnatal enamel. The findings suggest that thyroid hormone influences enamel maturation. Further, alterations in enamel structure, presumably due to prenatal thyroid deficiency, were found to be more common among children with neurological abnormalities at the age of 7 to 9 years.     

CONGENITAL HYPERPARATHYROIDISM AND VITAMIN D DEFICIENCY SECONDARY TO MATERNAL HYPOPARATHYROIDISM

Abstract. A new case of congenital hyperparathyroidism secondary to maternal hypoparathyroidism is described. Neonatal roentgenograms of the skeleton showed severe bone demineralisation and the distal metaphyses of the long bones were spread, frayed and cupped. Elevated levels of serum immunoreactive parathormone (iPTH) were found at the age of 41 days=270 μlEq/ml (Normal: <50 μlEq/ml). A very low plasma 25-OH-D concentration (<4 ng/ml) was found at the same time in spite of previous administration of 600 units of vitamin D every day for 18 days and in spite of healing of the bone lesions. At the age of 3 months, 15 mg of vitamin D was given orally: iPTH levels which remainded high 3 weeks before (210 μlEq/ml) were found to be normal one week after this vitamin D load (37 μlEq/ml). It is suggested that in congenital hyperparathyroidism secondary to maternal hypoparathyroidism, hyperparathyroidism increases the infants needs for vitamin D. This could result in a state of vitamin D deficiency which in turn would maintain the parathyroid hyperactivity.     

PRIMARY AND SECONDARY MATERNAL CYTOMEGALOVIRUS INFECTIONS AND THEIR RELATION TO CONGENITAL INFECTION

ABSTRACT. 4382 new mothers were examined retrospectively with the enzymelinked immunosorbent assay (ELISA) for IgG activity to cytomegalovirus (CMV) during pregnancy. Some of them were also studied with the indirect immunofluorescence (IIF) test for CMV-IgM antibodies. All the infants had been studied for CMV excretion within the first week of life. Nineteen of them had been shown to be congenitally infected with CMV. 1218 (28 %) women lacked CMV-IgG activity at their first antenatal visit (usually in months III-IV). Fourteen of them seroconverted before parturition (primary infection). Thirteen of the seroconverters were shown to develop CMV-IgM activity. In 6 (43 %) cases the primary infection was transmitted to the offspring. The remaining 13 congenitally infected infants were born to mothers with a positive IgG-test at their first antenatal control. Only one of these mothers had a clearly positive IgM-test. She was shown to lack CMV-antibodies before conception (primary infection during the first trimester). Preconceptional sera were obtained from further 4 of the 13 seropositive mothers of congenitally infected infants; all 4 had CMV antibodies before pregnancy (secondary infection during pregnancy). The combined studies of the mothers and infants revealed that 21–63 % of the congenital infections could have been caused by secondary maternal infections. Prospectively performed, the study would only have disclosed one of the three fetal CMV infections that resulted in neurological sequelae.     

北京市20年新生儿疾病筛查回顾性分析

目的分析北京市1989—2009年新生儿先天性甲状腺功能减退症（CH）和苯丙酮尿症（PKU）的筛查结果,为进一步提高新生儿疾病筛查的管理水平及干预措施提供依据。方法 采集出生72h后、正常哺乳的新生儿足跟血于特定滤纸上,进行CH及PKU筛查。PKU筛查检测指标为血苯丙氨酸（Phe）浓度,分别采用细菌抑制法（1989—2003年）和荧光法（2004—2009年）;CH筛查检测指标为血促甲状腺激素（TSH）水平,分别采用放免法（1989—2003年）及时间分辨荧光免疫分析法（DELFIA）（2003—2009年）。结果 1989—2009年,北京市共筛查新生儿1745998名,筛查率由1989年的14.01%提高到2009年98.16%,可疑患儿复诊率由1991年的65.85%提高到2009年的92.18%,共确诊CH482例,发病率1：3622;PKU192例,发病率1：9094。结论 新生儿疾病筛查是包括管理、筛查、随访、诊治、评估、教育等多个环节的系统服务工程,各部门的协调配合是提高筛查管理质量的有效措施,完善的新生儿疾病筛查工作可有效降低残疾儿的发生。     

Congenital Hypothyroidism: Physiological and Psychological Factors in Early Development

Children diagnosed as congenitally hypothyroid and treated from a very early age were followed up at 1 and 3 years. At 1 year they seemed to be developing normally, unless they were undertreated or had an additional disorder. There were no significant correlations between biochemical or social factors and psychological outcome at 1 year. At 3 years, however, those children whose T4 and/or T3 had been very low initially had significantly lower IQ scores than both other hypothyroid children and matched controls. Children with only moderately low initial T4 and/or T3, however, were doing just as well as their matched controls. Initial levels of TSH, the number of symptoms at first clinical interview and the age at the start of treatment were not good indicators of ability at 3 years. Undertreatment was rare but did appear to affect ability. Psychological outcome at 3 years was also correlated with social class (for both cases and controls). Multiple regression analyses indicated that both low initial T4 (less than 20 nmol/l) and social class contributed significantly to outcome.     

PRIMARY HYPOTHYROIDISM, GROWTH HORMONE DEFICIENCY AND CONGENITAL MALFORMATIONS IN A CHILD WITH THE KARYOTYPE 46, XY, del(l)(q25q32)

Abstract. Primary thyroidal hypothyroidism, growth hormone deficiency, congenital malformations and mental retardation occurred in a child with an interstitial deletion of one of the No. 1 chromosomes. Two bands were missing, so that the karyotype could be written: del(l)(pter→q25::q32→qter). The possible relationship between the clinical features and chromosomal deletion are discussed.