Increased incidence of congenital hypothyroidism due to iodine deficiency

BACKGROUND: The incidence of congenital hypothyroidism (CH) is expected to be elevated in iodine-deficient areas. In this study, the authors aimed to determine the incidence of transient and permanent CH in a large city which is known to be in the zone of moderate iodine deficiency. METHODS: Newborn babies in Bursa, Turkey, were screened by measurement of serum thyroid-stimulating hormone (TSH) obtained by heel prick. The babies who had a serum TSH >20 mIU/L were recalled for measurement of T4 and TSH in venous serum. RESULTS: A total of 11 770 newborns were screened over a period of 9 years. The incidence of CH was found to be 1/840. However, after excluding the transient cases, permanent CH was diagnosed in 1/2354. It was impossible to distinguish transient patients from permanent CH by initial laboratory tests (P > 0.05). The estimated power of the study in determining the incidence of CH in the population was 90% (P < 0.05). CONCLUSION: The authors conclude that the incidence of CH is very high in their population which warrants a country-wide neonatal screening program. Since transient cases cannot be distinguished and untreated transient hypothyroidism may also cause mental retardation, treatment must be started as early as possible with frequent monitoring to optimize the outcome and identify the transient patients.     

Higher incidence of thyroid agenesis in Mexican newborns with congenital hypothyroidism associated with birth defects

Background

Congenital hypothyroidism (CH) is the most common endocrine system disorder in newborns. Ectopic thyroid and agenesis are the most frequent thyroid structural malformations. Several reports have shown that CH is associated with birth defects (BD) ranging from congenital heart disease to ocular and gastrointestinal anomalies.

Aims

We investigated how many and what types of BD were associated with CH in Mexican children.

Study design

Cross-sectional study conducted in patients with confirmed CH.

Setting

Highly specialized government pediatric center in Mexico City.

Subjects

We included 212 patients with permanent CH identified by newborn screening.

Results

We found that 24% of patients with CH also had BD, and that there was a higher prevalence of thyroid agenesis in the group of patients with CH associated with BD (CH + BD) versus the isolated CH group (p = 0.007). There were more females than males in both groups. The most common BD were congenital heart diseases, especially those of the atrial septum, followed by patent ductus arteriosus, found as a single malformation or as part of a complex congenital heart disease. In this study, we found Hirschsprung disease, Beckwith-Wiedemann syndrome, Pierre Robin sequence, Albright's osteodystrophy, VATER association, and frontonasal dysplasia associated with CH.

Conclusions

In this study population, there was a high prevalence of BD in patients with permanent CH. Thyroid agenesis was the main etiological cause of CH in patients with associated congenital malformations. The high prevalence of CH + BD underlines the need for a comprehensive clinical diagnostic approach of the patients with CH.     

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.     

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.     

Outcomes of neonates with congenital heart disease

One of the most important advances of the past 10 to 15 years in the field of pediatric cardiology is the improvement in prognosis for neonates with complex congenital heart disease. During the past 18 months, several publications have addressed outcomes in neonates with congenital heart disease. Many of these reports demonstrate continuing improvement in preoperative, early postoperative, and late postoperative survival among patients with complex neonatal heart defects. Other reports shed substantial new light on late functional outcome, especially neurodevelopmental status. In addition to data on survival, morbidity, and functional status, we discuss developments in perioperative evaluation and management that are likely to further the trend toward improved outcome for neonates with complex congenital heart disease.     

Definitive diagnosis in children with congenital hypothyroidism

OBJECTIVES: To investigate the definitive diagnosis and underlying causes of congenital hypothyroidism (CH) in eligible children through the use of a standardized protocol. STUDY DESIGN: Children > or =3 years of age with CH without an identified permanent cause underwent a diagnostic algorithm. Eligible subjects had an anatomically normal thyroid or had not undergone imaging studies. After thyroxine was discontinued for 4 weeks, thyroid function tests and a thyroid ultrasound were obtained. An abnormal ultrasound was followed by a (99m)Tc thyroid scan. A perchlorate washout test was performed in subjects with a normal ultrasound but abnormal thyroid function tests. Children with normal results were followed for 1 year. RESULTS: Of 33 children, 17 were boys. Nine (27%) had an absent or ectopic thyroid, 12 (36%) had dyshormonogenesis, and 12 (36%) had transient CH. Average thyroxine dose before medication discontinuation was 2.9 +/- 0.83 microg/kg in permanent cases versus 2.0 +/- 0.53 microg/kg in transient (P <.002). No complications from discontinuation of thyroxine occurred. CONCLUSIONS: A significant percentage of children with CH have a transient requirement for thyroid hormone. A standardized protocol with thyroid ultrasonography is a safe and sensitive approach to a trial off of thyroxine in select patients.     

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     

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.     

The screening programme for congenital hypothyroidism in Greece: evidence of iodine deficiency in some areas of the country

Newborn screening for Congenital Hypothyroidism, using TSH measurement in dried blood spots, was started in Greece in 1979. A total of 1,274,000 neonates have been screened and 377 cases of Congenital Hypothyroidism were detected, for an incidence of 1:3370. Employing a cut-off point of 30mU/L of TSH in whole blood, 0.3% of the infants were recalled for repeat examination. The sensitivity of the screening test was 0.99 and the predictive value of a positive test 0.1. The frequency of "false positive" cases in the different geographic regions of Greece showed wide variation between the south and the north areas of the country. We suggest that these differences reflect the degree of iodine deficiency in the population and may be used as an epidemiological indicator of this deficiency.     

Thyroid disorders in neonates: A practical approach to congenital hypothyroidism and thyrotoxicosis

Congenital hypothyroidism is one of the most common causes of preventable intellectual disability in the UK and worldwide. Early diagnosis is critical to allow for early intervention. At present, 1 in 2000 to 1 in 3000 babies born in the UK have congenital hypothyroidism. Of these, most will not display any clinical manifestations or symptoms in the first few weeks of life. In short, babies will develop intellectual disability if they go undiagnosed. It is therefore no surprise that the day 5 blood spot is essential for good outcomes and harm reduction. Diagnosis of thyroid disorder is based on measuring the thyroid hormones and thyroid stimulating hormone levels. The most common cause of congenital hypothyroidism is an abnormality in thyroid gland development (dysgenesis) but it may also be the result of a defect in thyroid hormonogenesis or may be temporary as a result of maternal medications passing through the placenta, maternal blocking antibodies or iodine excess or deficiency. Rarely, it is the result of pituitary or hypothalamic abnormality when it is called central or secondary/tertiary hypothyroidism. This short article offers practical advice on how to diagnose and treat congenital hypothyroidism and how to interpret the results of available biochemical tests.     

Use of saphenous vein allografts for aortopulmonary artery anastomoses in neonates with complex cyanotic congenital heart disease

Summary A saphenous vein allograft was used to create an aortopulmonary communication in 16 infants with cyanotic congenital heart disease and ductus-dependent pulmonary blood flow. These grafts measured from 3 to 8 mm in diameter and were placed between the aorta and main pulmonary artery in eight patients, between aorta and right pulmonary artery in eight, and between aorta and left pulmonary artery in one (one child had two grafts). Before heparin was used, early in the series, four of these grafts occluded and three of the four infants died during attempted revision. Another infant died early from renal failure. Late mortality has claimed four: one from cerebral hemorrhage, two from hypoxia, and one at open-heart surgery for repair. There are eight late survivors (50%).Most of the allografts were used before small diameter Gore-Tex was available; in more recent patients, 4- to 6-mm Gore-Tex grafts have been used. In our most recent patient, however, the attempt to place a Gore-Tex graft was unsuccessful, but the more pliable saphenous vein graft was readily placed and an adequate shunt obtained. Both the saphenous vein graft and the Gore-Tex have the advantage of providing pulmonary flow without the higher risk of congestive failure or pulmonary hypertension seen in patients with a Waterston or Potts anastomosis. They are easier to perform, require less anesthesia time than the Blalock-Taussig shunt, last as long as the Blalock-Taussig when done under similar conditions, and are easy to take down at the time of total repair.     

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.     

暂时性甲状腺功能减低伴甲状腺肿大患儿DUOX2基因突变的研究

目的 研究暂时性先天性甲状腺功能减退伴甲状腺肿大患者DUOX2基因突变情况.方法 对5例暂时性甲状腺功能减低伴甲状腺肿大患者DUOX2基因的全部外显子进行基因突变筛查,基因突变类型和特点.结果 在1例先天性甲状腺功能减低症( Congenital Hypothyroidism,CH)患儿中发现DUOX2基因一个等位基因的杂合性突变,为第10外显子cDNA的1329位点发生C＞T的突变(c.C1329T),导致第376密码子精氨酸突变为色氨酸(p.Arg376Trp).其他4例CH患儿均没有发现DUOX2基因突变.结论 在先天性甲状腺功能减退患儿中也发现了DUOX2基因的p.Arg376Trp突变,该突变的单个等位基因剂量的改变可能导致先天性甲状腺功能减退.     

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.     

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。     

Incidence of iodine deficiency in Turkish patients with congenital hypothyroidism

Background: Turkey is located in an area of mild to moderate iodine deficiency. The aim of the present study was to investigate the incidence of iodine deficiency in patients with congenital hypothyroidism.
Methods: Twenty five patients with a median age of 12 days (6 days–6 months) at diagnosis and followed for a median time of 7 months (1–60 months) were enrolled in the study. Thyroid function tests, thyroid scintigraphy, ultrasonography and urine iodine measurements of the patients and mothers were performed.
Results and conclusion: Congenital hypothyroidism was diagnosed within postnatal day 13, between days 13 and 30, and after 30 days of age in 68%, 20% and 12% of the patients, respectively. At the time of diagnosis mean serum thyroid-stimulating hormone and total T4 were 85.3 ± 27.6 mIU/L and 3.9 ± 2.8 μg/dL, respectively. Incidence of iodine deficiency was 36% in the patients (median, 110 μg/L) and 88% in the mothers (median, 40 μg/L). Thyroid scintigraphy and ultrasound were normal in all of the patients with iodine deficiency. At scintigraphic evaluation, thyroid gland was not visualized in 28% of patients; in the patients whose thyroid glands were not visualized scintigraphically thyroid ultrasonography indicated agenesis in 57%, and hypoplasia in 43%. In all the patients with thyroid agenesis or hypoplasia iodine levels were normal. In 36% of the patients imaging studies of thyroid gland and urine iodine measurements were normal. Despite salt iodization program, incidence of iodine deficiency is still high in patients with congenital hypothyroidism and mothers. National measures are urgently required for correction of iodine deficiency in Turkey.