先天性甲状腺功能减低症治疗时机的疗效评估

目的 探讨小儿先天性甲状腺功能减低症(以下简称先天性甲低)治疗时机评估及其与预后情况.方法 对1998年5月至2008年12月在广东省深圳市人民医院儿科内分泌专科门诊就诊的68例治疗随访时间超过2年的先天性甲低患儿的体格检查和智能测定进行分析,以评估不同治疗时机对其预后的影响.筛查组47例,开始治疗年龄13～59 d;非筛查组21例,开始治疗年龄6个月至14岁.结果 先天性甲低患儿的身高、体重与智能发育筛查组与非筛查组比较差异有统计学意义(P均<0.01),遗留智能残疾的发生率两组比较差异亦有统计学意义(P<0.01).结论 对先天性甲低患儿实施治疗的时间越旱,智能发育和体格发育越好,遗留智能残疾的发生率越低.     

A case of congenital hypothyroidism in PHACE syndrome

Although hemangiomas, benign tumors of vascular origin, are very common among children and represent the most frequent benign tumor at that age, their association with other malformations constitutes a rare neurocutaneous disorder called PHACE syndrome. This condition is characterized by posterior fossa anomalies, hemangioma of the face, arterial alterations, cardiac defects, and eye anomalies (as represented by the acronym PHACE); sternum defects, endocrinopathies, and thyreopathies may be present as well. In this report, we describe a case of congenital hypothyroidism due to an empty thyroid site, as demonstrated by ultrasound, in an Italian child.     

Umbilical cord blood TSH levels in term neonates: a screening tool for congenital hypothyroidism

This study was conducted to find normative values for thyroid stimulating hormone (TSH) in 1200 cord blood samples of term babies whose mothers were not on any thyroid medications. TSH was estimated within 24 hrs by enzyme immunoassay. A full thyroid profile, viz, T3, T4, TSH, fT3 and fT4 was done at 7-10 days of age in all babies with cord TSH >20 mIU/L. The mean, median and standard deviation for the TSH values for the cohort were 6.13 mIU/L, 5.8 mIU/L and 4.523 respectively. 22 babies with TSH values >20 mIU/L were given repeat tests. Hypothyroidism was confirmed in two of these babies. We conclude that a cut off value of TSH >20 mIU/L is adequate for neonatal thyroid screening in Indian settings.     

Intellectual development at 10 years in early treated congenital hypothyroidism.

Fifty nine children born between 1978 and 1981 with congenital hypothyroidism detected by neonatal screening were assessed at 10 years using the Wechsler intelligence scale for children, together with 59 matched classroom controls. Thirty one children with severe hypothyroidism who had pretreatment plasma thyroxine concentrations of 40 nmol/l or less had a mean (SD) full scale IQ score of 104.7 (15.1), compared with a mean (SD) score of 114.6 (16.3) for the 28 less severely affected children who had pretreatment thyroxine levels greater than 40 nmol/l, and mean (SD) scores of 114.5 (12.8) and 114.8 (13.8) respectively for the 31 and 28 control children. In the hypothyroid children the IQ scores at 10 years were closely related to the IQ scores at 5 years and at 3 years. It is concluded that the deficit in IQ score found at 3 and 5 years in children with severe hypothyroidism is still evident at the age of 10 years.     

Intelligence,motor skills and behaviour at 5 years in early-treated congenital hypothyroidism

The cognitive functioning, motor skills and behaviour of 5-year-old children with early-treated congenital hypothyroidism was assessed. The study group was 57 children with congenital hypothyroidism (CH) diagnosed by neonatal screening in N.E. and N.W. Thames regions between 1978 and 1981 along with 51 non-affected controls matched for age, sex, social class and language background. Small differences in I.Q. and behaviour between the patients and the controls were not statistically significant. However, children with CH showed significant deficits in motor skills (M 79.9 SE 3.7) compared to the controls (M 99.8 SE 4.0) (P=0.0003). Deficits were particularly marked for balance. In addition, children with more severe hypothyroidism at diagnosis (Plasma thyroxine <20 nmol/l) did significantly less well in respect to I.Q. and motor skills than those with less severe hypothyroidism (plasma thyroxine >60 nmol/l). These findings provide further evidence for the importance of the severity of hypothyroidism in determining the outcome for intelligence and motor skills in children with early-treated congenital hypothyroidism. Deficits in motor skills, particularly in relation to balance, suggest that early impairment of the vestibular system may occur despite early treatment.     

甲状腺相关基因突变与先天性甲状腺功能低下症

先天性甲状腺功能低下症(CH)是引起儿童生长和神经发育障碍的常见内分泌疾病,主要由先天性甲状腺发育异常或甲状腺激素合成异常所致。近年来研究发现,部分CH患者存在甲状腺发育或甲状腺素合成相关基因的突变,文章就上述基因的生物学功能,基因突变患者的临床特征作一介绍。     

Etiologic diagnosis of congenital hypothyroidism and plasma thyroglobulin

Plasma thyroglobulin (Tg) measurement at the time of screening has a great value in the classification of congenital thyroid defects. Tg was measured in a group of 100 children with congenital hypothyroidism (athyreosis n = 15, ectopic n = 59, eutopic n = 26). Tg was undetectable in athyreosis. These values were significantly different (2.46 +/- 2.52 ng/ml) from those in the group of ectopic (111 +/- 139 ng/ml) and in the group of eutopic (196 +/- 312.1 ng/ml). Four patients with eutopic glands had non measurable Tg and may represent cases with congenital Tg defect.     

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.     

Microfollicular thyroid adenoma and congenital goitrous hypothyroidism.

Three patients with congenital goitrous hypothyroidism are reported. They were treated with adequate thyroxine replacement and developed well defined microfollicular thyroid adenomas despite being euthyroid clinically and biochemically throughout their clinical course. Patients with congenital goitrous hypothyroidism appear to be at increased risk of developing thyroid adenoma in childhood despite the use of replacement thyroxine treatment in physiological doses.     

Thyroxine hair content in congenital hypothyroidism and hyperthyroidism

Using the determination of thyroxine (T4) hair content, we studied 16 hypothyroid newborns diagnosed by means of our regional screening program, and five hypothyroid infants, undetected at birth, at diagnosis and after 3 months of substitutive therapy (8-10 microg/kg/day L-thyroxine in newborns; 15 microg/kg/day in infants), and 13 hyperthyroid adults. Hair T4 content was similar at diagnosis in hypothyroid newborns (2.6 +/- 2.3 pg/mg hair) and in infants undetected at birth (2.4 +/- 1.7 microg/mg hair), but very high only in the latter after therapy (23.2 +/- 3.9 microg/mg hair). Untreated hyperthyroid adults surprisingly evidenced lower hair T4 (0.4 +/- 0.2 microg/mg hair) than controls (1.5 +/- 0.3 microg/mg hair). We suggest these findings are due to differential tissue storage of thyroid hormone, related to the different blood T4 concentration. Therefore, T4 hair assay could be a non-invasive method to further assess thyroid status.     

Outcome of ventilated infants born at term without major congenital abnormalities

The longer-term outcome of term-born infants without congenital anomalies requiring ventilation in the first 24 h after birth has rarely been reported. Our aims were to determine the mortality and long-term morbidity of such infants and identify risk factors for adverse outcome. The outcomes of 43 of 45 infants born at term consecutively requiring mechanical ventilation were reviewed. The infants had: meconium aspiration syndrome (n = 11), hypoxic ischaemic encephalopathy (HIE) (n = 11), respiratory depression (n = 12), sepsis (n = 5), persistent pulmonary hypertension of the newborn (n = 3) and middle cerebral artery infarction (n = 1). Eleven infants developed seizures (26%), 13 (30%) had abnormal electroencephalograms and 11 (26%) had abnormal MRI scans; 26% had an adverse outcome: six died, and five had severe neurodisability at 2 years. The infants with congenital toxoplasmosis and a middle cerebral artery infarction were excluded from the prediction analysis. In the remaining 41 patients, requirement for anticonvulsants (relative risk, RR = 4.44, 95% CI = 1.48 to 12.70; p = 0.014) and prolonged ventilation (longer than 3 days) (RR 4.83, 95% CI 1.51 to 15.64) predicted adverse outcome. Infants with HIE had an increased risk of adverse outcome (relative risk 5.45, 95% CI 1.01 to 33.85), but an adverse outcome occurred in infants with other diagnoses. Conclusion: Mortality and neurodisability at follow-up were common in infants born at term without major congenital anomalies who required mechanical ventilation in the first 24 h after birth, particularly in those who developed seizures requiring treatment and prolonged ventilation.     

A ten-year temporal analysis of primary congenital hypothyroidism in Israel.

It was previously shown that some congenital malformations present seasonal variations, suggesting a seasonal etiology such as viral infections. Some earlier studies have shown a certain degree of variation in the incidence rates of congenital hypothyroidism. As from April 1978 all infants born in Israel were screened for congenital hypothyroidism (CH) in one central laboratory at the Sheba Medical Center Tel-Hashomer. During the 10-year screening period (April 1978 to March 1988) 303 infants were found to have primary CH, which constitutes an overall incidence of 1/3192 live births. The annual and monthly birth incidence was calculated for the 120 months of the screening period. The annual CH incidence was significantly low in 1978 and 1979 and significantly high in 1985. There were wide and significant variations in the individual monthly incidences of CH. The average monthly incidence showed a low peak in August; however the autocorrelation analysis of the monthly incidences of CH showed no significant periodicity. This was supported by the Fourier analysis which showed no distinctive frequency peak. The last menstrual period was calculated for 138 of the infants' mothers and an autocorrelation analysis of these dates showed no significant periodicity. These results support a non-periodic etiology for sporadic primary CH in Israel.     

A high prevalence of consanguineous and severe congenital hypothyroidism in an Iranian population

To determine the incidence of permanent congenital hypothyroidism (CH) in Tehran and Damavand, cord blood spots were collected from February 1998-August 2002 and infants with TSH > or =20 mU/l were recalled. CH was confirmed in neonates (aged > or =7 days) with serum TSH >10 mU/l and T4 <84 nmol/l. Cases were followed up until September 2003. Dysgenesis was detected by thyroid imaging. In eutopic cases, serum TSH and T4 measurements following levothyroxine discontinuation (2-3 years of age) confirmed dyshormonogenesis and transient CH. Of 35,067 neonates, 373 (1.06%) were recalled and 25 (1:1,403 births) had permanent CH (six had transient CH and four remain unknown). Dysgenesis was detected in 18 (1:1,948 births) and dyshormonogenesis in seven (1:5,010 births) infants. Parental consanguinity was present in 10 (55.6%) dysgenetic, three (42.9%) dyshormonogenetic, and overall 6,648 (28.6%) of 23,227 screened infants. Odds ratio (95%CI(OR)) of consanguinity in permanent CH and dysgenesis was 2.75 (1.17-6.47) and 3.74 (1.33-10.52), respectively. The high prevalence of parental consanguinity in infants with permanent CH warrants genetic assessment.     

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.