Hypothalamo-pituitary hypothyroidism detected by neonatal screening for congenital hypothyroidism using measurement of thyroid-stimulating hormone and thyroxine

The optimal strategy in neonatal screening for congenital hypothyroidism is still a subject of controversy. In Kanagawa Prefecture in Japan, simultaneous thyroid-stimulating hormone (TSH) and T4/fT4 determination has been used, while the results of our program may provide valuable information. Cumulative findings were analysed to determine the type and frequency of thyroid disorders in infants detected by simultaneous TSH and T4/fT4 determination, and the TSH and T4/fT4 screening strategy was validated. A total of 1284130 neonates were screened between October 1979 and September 1997 and infants followed because of low T4/fT4 without elevated TSH (T4 < 51.5 nmol/L or fT4 < 9 pmol/L and TSH < 15 mU/L) were retrospectively analysed. The first survey was carried out within 6 mo of birth and the second in 1998; 258 infants were diagnosed with congenital hypothyroidism at the first medical evaluation, 15 of them with hypothalamo-pituitary hypothyroidism. However, in the second survey, only 8 children were confirmed as having hypothalamo-pituitary hypothyroidism, therefore the incidence detected by the present strategy was 1/160516. Of 8 children with hypothalamo-pituitary hypothyroidism, mental retardation was prevented in 3 owing to early treatment. CONCLUSIONS: Simultaneous measurement of TSH and T4/fT4 is a useful strategy for detecting hypothalamo-pituitary hypothyroidism, but more studies are needed to show the cost-benefits of using this strategy.     

Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism

Heyerdahl S, Kase BF, Stake G. Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism. Acta Prediatr 1994;83:618–22. Stockholm. ISSN 0803–5253
The aim of this investigation was to study if bone age development (assessed by the Greulich & Pyle atlas) was related to L-thyroxine treatment in 47 children with congenital hypothyroidism, treated early and according to general recommendations. In spite of frequent delay in skeletal maturation at diagnosis, the delay in mean bone age at a mean chronological age of 1.5 years was slight (0.5 months), and 30% of the variation in bone age SD score (SDS) at 1.5 years was accounted for by the dose of L-thyroxine and serum thyroxine during the first year. The children with a bone age within ± 1 SDS had a prescribed mean dose of L-thyroxine per kg body weight from 3 to 12 months of age of 5.4 ± 1.7 pg/kg/day, and their mean serum thyroxine concentration during the first year was 175 ± 29 nmol/l. We conclude that bone age at 1.5 years of age was positively correlated with the dose of L-thyroxine and the serum thyroxine concentration during the first year. This supports the general use of bone age assessments as a complement to other treatment variables in the follow-up of children with congenital hypothyroidism.     

Significance of elevated serum thyrotropin during treatment of congenital hypothyroidism

Serum thyrotropin concentrations are frequently elevated during treatment of children with congenital hypothyroidism. It is unclear if elevated thyrotropin during early treatment indicates non-optimal treatment. In a cohort of 49 children with congenital hypothyroidism, we studied the decline in serum thyrotropin concentration after initiating L-thyroxine treatment, the relationship between elevated thyrotropin and treatment variables, and non-compliance with the treatment as a possible cause of elevated thyrotropin. The initial mean dose of thyroxine was 8.5 (SD 3.3) μg/kg body weight/day: 71 % of the serum samples obtained 15-21 days after the start of treatment had serum thyrotropin concentrations < 10 mU/1. Six children had no samples with serum thyrotropin < 10 mU/1 during the first 3 months of treatment. These children had a lower thyroxine dose prescribed, and serum thyrotropin was normalized when the dose was sufficiently increased. During treatment, from 6 weeks of age, serum thyrotropin > 10 mU/1 was related to a lower dose of thyroxine and lower serum thyroxine, and was not due to non-compliance with treatment.     

Linear growth in early treated children with congenital hypothyroidism

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment ( r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine <40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment ( r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year ( r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.     

Screening for congenital hypothyroidism in France

Misdiagnosed cases of congenital-hypothyroidism (CH) during the first 9 years of the French screening program were analysed. A total of 50 cases were missed (3% of total diagnosed) which represents a severe failure of the system. Failures were caused by technical errors of sample collection or TSH assay (n=27) or due to normal TSH (n=22) or T₄ (n=1) concentrations in the newborn blood specimens. We conclude that screening methods should be improved and that physicians should remain alert to clinical signs of hypothyroidism.     

Screening for congenital hypothyroidism in Turkey

Abstract A pilot study was performed to determine the incidence of congenital hypothyroidism (CH) in Turkey and to build a model for nationwide screening. From December 1991 to December 1992, 30097 newborns were screened for CH using a primary measurement of thyroid stimulating hormone in capillary blood on days 3–5 of life. Samples were obtained in collaboration with the ongoing nationwide phenylketonuria screening programme. Eleven cases of primary CH were detected giving the incidence of 12736. Recall rate was 2.3%. Replacement therapy withl-thyroxine was started after the confirmation of diagnosis. The median age at the initiation of replacement therapy was 23 days (range 7–35 days).Conclusion The incidence of CH is notably higher in Turkey than reported in most other countries. Iodine deficiency and/or dyshormonogenesis might contribute to this high incidence. This result emphasizes the necessity of a nationwide screening programme.     

Thyrotrophin-blocking antibodies in congenital hypothyroidism

The role of transplacental transfer of maternal thyrotrophin (TSH)-blocking antibodies causing congenital hypothyroidism in Southern Chinese children was examined in this study. Twenty-two mothers of 24 patients with congenital hypothyroidism were studied 3-5 years after delivery. None of them had thyroid dysfunction at delivery or at the time of study. None had antithyroglobulin or antimicrosomal antibody. Only one mother was found to have TSH-binding inhibitory immunoglobulin (TBII), and her child had agenesis of the thyroid. This women had Graves disease in remission for 2 years before delivery. None had TSH-stimulated cAMP response inhibitory immunoglobulin (TSII). Ten of the 24 congenital hypothyroid children had transient neonatal hypothyroidism, seven had agenesis of the thyroid, six had dyshormonogenesis and one had a sublingual thyroid. As none of the mothers who had children with transient neonatal hypothyroidism had blocking antibodies at the time of study, the aetiology of the transient neonatal hypothyroidism remains unclear. These data suggest that maternal TSH-blocking antibodies do not play a role in most cases of sporadic congenital hypothyroidism.     

Neonatal screening for congenital hypothyroidism and phenylketonuria in China

Background  Neonatal screening is helpful to prevent serious disabitily and sufferings caused by congenital or inherited disease. This study was to review the status of neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) in China. Methods  We analyzed data of neonatal screening for CH and PKU in the past two decades which were obtained from the national network of neonatal screening centers collected by the National Center for Clinical Laboratory. Results  Of 18.8 million newborns screened from 1985 to 2007, 9198 were identified with CH, giving a prevalence of 1/2047. In 19.0 million newborns screened in the same period, 1638 had PKU, with a prevalence of 1/11 572. An increasing number of neonates have been subjected to neonatal screening in China annually during this period. Data from Zhejiang Neonatal Screening Center showed that the recall rate of neonates suspected with CH and PKU was 95.52% in 2007. Confirmatory tests were performed and treatments were initiated in most of the neonates with CH and PKU within a month after birth. Conclusions  More governmental support at different levels is needed to make neonatal screening more efficient. The screening should be improved with a satisfactory control system including shorter time of report and a higher recall rate.     

Permanent and transient congenital hypothyroidism in preterm infants

Aim: Transient fluctuations in thyroid function are well recognized in preterm infants. We wanted to assess TSH variation in babies with transient and permanent congenital hypothyroidism (CHT). Methods: Whole bloodspot TSH data in preterm infants (<35 weeks; 2005–2010) were assessed, and infants with bloodspot TSH values >6 mU/L identified. Permanent CHT was defined as a requirement for thyroxine beyond 3 years of age. Results: A first TSH sample was obtained from 5518 infants (median gestational age, 32 w; range, 22–35), with a second sample obtained from 5134 infants (median gestational age, 32 w; range, 22–35). Five infants had raised TSH concentrations on both occasions. Three of the five infants had a serum TSH >80 mU/L on second screen but two came off thyroxine beyond 3 years of age. All preterm babies with permanent or transient hypothyroidism were detected by the first TSH cut‐off of 6 mU/L. Only one infant with a birth weight <1500 g remains on thyroxine treatment beyond 2 years of age. Conclusions: The incidence of permanent CHT in preterm infants is similar to term infants. Profound abnormalities of thyroid function can occur in preterm babies with transient hypothyroidism but both categories of hypothyroidism can be detected by a ‘once‐only’ TSH screening strategy with a relatively low cut‐off.     

Screening for congenital hypothyroidism in Hong Kong

A pilot cord blood TSH screening program for congenital hypothyroidism was commenced in Hong Kong in April 1982. By April 1984, 14 411 neonates born in two hospitals were screened for this disorder. Five cases of primary hypothyroidism and two cases of transient hypothyroidism were detected. The detection of cases of congenital hypothyroidism with only moderately elevated cord blood TSH values means that the recall rate will remain high.     

Transient congenital hypothyroidism after amniofetography

A newborn infant who presented with goitrous congenital hypothyroidism is described. Thyroid dysfunction was due to amniofetography performed 4 days before delivery, during which a total of 5.22 g of iodine as water- and lipid-soluble contrast medium was injected. After oral l-thyroxine treatment hypothyroidism disappeared rapidly. Thyroid function remained normal when treatment was withdrawn after 28 days, underlining the transient character of hypothyroidism.     

Psychomotor development in congenital hypothyroidism

In 1979 a national screening programme for congenital hypothyroidism (CH) was introduced in Greece. Treatment with l-thyroxine was started immediately after confirmation of the diagnosis, at a median age of 28 days. A standardized development test (Griffiths) was given to a group of CH infants and to healthy controls at the ages of 5–7, 11–13, 17–19, and 23–25 months. Thirty-three infants with CH were also studied at the age of 35–37 months. The mean developmental quotient of CH infants was 103.8±12.0, 100.9±10.1, 103.3±7.1 and 99.8±10.2 from the ages of 5–7 to 23–25 months, and was not statistically different from those of the controls. Statistical analysis showed no significant differences between athyreotic children and those with an ectopic gland. Our findings show that the prognosis for psychomotor development of children with CH is quite good, provided that treatment starts in the first 6 weeks of life.Abbreviations (CH) congenital, hypothyroidism - (PD) psychomotor development - (T₄) thyroxine - (TSH) thyrotropin - (DQ) developmental quotient - (SD) standard deviation     

替代治疗后先天性甲状腺功能减低症患儿的气质特征初步探讨

目的探讨替代治疗后先天性甲状腺功能减低症患儿的气质特征。方法2004—2005年采用中国婴儿气质量表对在深圳市妇幼保健院确诊的25例替代治疗后先天性甲状腺功能减低症患儿和145例正常儿童进行测查。结果先天性甲状腺功能减低症患儿组D型、S型和中间型比例较多,与对照组间差异有显著性。在活动水平、节律性、适应性、持久性、注意分散、反应阈6个维度的得分上与对照组比较差异存在显著性。结论替代治疗后先天性甲状腺功能减低症患儿的气质有其独特性,其气质类型比正常儿童消极,应针对患儿的气质特点进行综合治疗。     

Audit of neonatal screening programme for phenylketonuria and congenital hypothyroidism

The performance of the neonatal screening programme was audited against clinical standards in the Bath clinical area from 1 April 1994 to 31 March 1996. The standards and policy were agreed by local service provider representatives of the screening and were audited, using laboratory and child health computer systems and medical records. Two annual reports were produced with recommendations for improvement communicated to representatives of the service. Thus the first audit loop has been completed.  The audit shows that the coverage of the service is excellent, with all eligible babies being offered screening; those with congenital hypothyroidism or phenylketonuria receive appropriate treatment by the 28 day standard. The process works extremely well, although areas for improvement have been identified, to increase the efficiency of the service.  It is concluded that an effective and efficient audit cycle can be established, to monitor and improve the performance of the neonatal screening service.