High prevalence of congenital hypothyroidism in the Greek Cypriot population: results of the neonatal screening program 1990-2000

OBJECTIVE: To evaluate the results of the screening program for congenital hypothyroidism (CH) in the Greek Cypriot population. CHILDREN AND METHODS: During 1990-2000, 109,532 neonates were screened by TSH determination. Permanent CH was proven with biochemical findings after discontinuation of treatment for scintigraphy at the age of 3 years. RESULTS: Permanent CH was diagnosed in 61 infants, incidence 1/1800, with female/male ratio 2.05/1. The most common clinical findings were omphalocele (61%), large anterior fontanelles (49%) and edema of the eyelids (34%). The more delayed the bone maturation, the lower were initial T4 levels (p = 0.005). Bone maturation tended to be more advanced in thyroid hypoplasia and more delayed in thyroid agenesis (p = 0.049). Scintigraphy of the thyroid with TC99 revealed ectopia in 38%, thyroid agenesis in 36%, thyroid hypoplasia in 24% and dyshormonogenesis in 1.7%. Children with transient CH had significantly lower T4 and higher TSH values initially compared to those with permanent CH after birth; initial TSH level, however, failed to predict the nature of CH. Children with transient CH required less thyroxine dosage to maintain normal thyroid hormone levels and they had a normal thyroid gland on scintigraphy. The TSH level was normalized before the age of 2 months with a starting L-thyroxine dose of 10 microg/kg/daily. CONCLUSIONS: The incidence of primary CH in Greek Cypriots is 1/1800 live births. The most common etiology is thyroid dysgenesis. Initial T4 levels correlated with the degree of skeletal maturation and the etiology. Initial TSH level, although lower in children with transient CH, could not predict the nature of CH.     

The use of L-T4 as liquid solution improves the practicability and individualized dosage in newborns and infants with congenital hypothyroidism

Dosage recommendations for the initial therapy of congenital hypothyroidism (CH) in newborns vary between 8 microg/kg/d and 10-15 microg/kg/d. AIM: To evaluate the practicability of LT4 in liquid form and to define the initial dosage for optimal treatment. METHODS: Liquid LT4 solution was administered to 28 consecutive newborns with primary CH. We measured TSH, T3, T4, free T3 and free T4 before therapy and during follow-up up to 2 years. After 2 years a standardized developmental test (Griffith) was performed. RESULTS: The median dosage at start of therapy was 12.3 microg LT4/kg/d and decreased to about 5 microg LT4/kg/d after 9 months. The median time of normalization of TSH (< or =6 mU/l) was 2 weeks. In 21 patients, who received a median starting dosage of 12.7 microg LT4/kg (range 9.8-17.1 microg/kg), TSH levels normalized within a median of 1 week. Seven patients receiving only 10.1 microg LT4/kg normalized their TSH only after a median of 2 months. CONCLUSIONS: Newborns with CH should normalize their TSH within 1-2 weeks. The initial dose necessary to normalize TSH is not lower when a liquid solution is used. The higher dose used in tablets is not due to inefficient absorption, but rather reflects the increased demand for thyroid hormone in the first weeks of life.     

Central Congenital Hypothyroidism Detected by Neonatal Screening in Sapporo, Japan (2000–2004): It’s Prevalence and Clinical Characteristics

In Sapporo, Japan, a neonatal screening program for congenital hypothyroidism (CH) has employed measurement of free thyroxine (T4) and TSH in the same filter-paper blood spot. This system has enabled us to identify primary CH and central CH during the neonatal period. The aim of this study was to clarify the prevalence and clinical characteristics of central CH. For this purpose, the screening program requested serum from infants with free T4 concentrations below the cut off value regardless of the TSH levels. Between January 2000 and December 2004, 83,232 newborns were screened and six central CH patients were detected as a result of follow-up of low free T4 and non-elevated TSH screening (1:13,872). This frequency is higher than in other studies. Four patients showed multiple pituitary hormone deficiency with pituitary malformations on magnetic resonance imaging. One patient was diagnosed as having Prader-Willie syndrome. The remaining patient was considered to have isolated central CH. Our study demonstrated that the frequency of central CH is 1:13,872. Free T4 measurement would also be advantageous in early recognition of multiple pituitary hormone deficiency.     

Initial treatment dose of L-thyroxine in congenital hypothyroidism

OBJECTIVES: To determine the optimal initial treatment dose of L-thyroxine in congenital hypothyroidism (CH) by evaluating the time course of rise of thyroxine (T(4)) and free T(4) concentrations into an established "target range" and normalization of thyroid-stimulating hormone (TSH) and to reevaluate the "target range" for T(4) and free T(4) concentrations during the first 2 weeks of CH treatment. STUDY DESIGN: Infants of birth weight 3 to 4 kg with CH (n = 47) detected by newborn screening were randomly assigned into three L-thyroxine treatment dose arms: 37.5 microg/day (group 1); 62.5 microg/day for 3 days, then 37.5 microg/day (group 2); and 50 microg/day (group 3). Serum T(4), free T(4), triiodothyronine (T(3)), free T(3), and TSH were measured before treatment and at 3 days and 1, 2, 4, 8, and 12 weeks after treatment. RESULTS: T(4) and free T(4) concentrations increased into the target range (10 to 16 microg/dL) by 3 days of therapy in infants in groups 2 and 3 and by 1 week in group 1; 50 microg/day (average 14.5 microg/kg/day) provided the most rapid normalization of TSH by 2 weeks. With the use of linear regression analysis of T(4) versus TSH or free T(4) versus TSH plots, the intercept at the lower range of normal for TSH (1.7 mU/L) showed T(4) = 19.5 microg/dL and free T(4) = 5.23 ng/dL. CONCLUSIONS: Initial dosing of 50 microg/day (12-17 microg/kg per day) raised serum T(4) and free T(4) concentrations to target range by 3 days and normalized TSH by 2 weeks of therapy. We recommend consideration of a somewhat higher "target range" of 10 to 18 microg/dL for T(4) and 2 to 5.0 ng/dL for free T(4) during the first 2 weeks of L-thyroxine treatment. After 2 weeks of treatment, the target range drops to 10 to 16 microg/dL for T(4) and 1.6 to 2.2 for free T(4).     

Tc]-99m thyroid scintigraphy in congenital hypothyroidism screening program

The aetiology of congenital hypothyroidism (CH) may be important in determining disease severity, outcome and treatment schedules because athyroid patients need higher treatment doses and close monitoring particularly early in life. The aim of this study was to evaluate thyroid scintigraphy (TS) findings in infants with CH and to determine the relationship of serum TSH and T4 values with thyroid agenesia, in an attempt to identify factors that may detect thyroid agenesia before treatment. Since August 2002 to April 2005, screening program for CH was carried out in the Isfahan University of Medical Sciences and Health Services, Isfahan, Iran. Screening was performed by measuring both the serums T4 and TSH concentration at day 3-7 of birth. Full-term newborns were recalled based on a serum TSH >20 mIU/l or serum T4 < 6.5 microg/dl and premature newborns based on T4 level by weight and TSH level by age. After repeating the laboratory test and clinical evaluation, Tc-99m TS was recommended for all infants with suspected CH before thyroxin replacement therapy. On the basis of Tc-99m TS, the thyroid gland was classified as normal scan, ectopic, goiter and athyrosis. TS results were compared with serum T4 and TSH levels. Of 93 381 newborns screened over a period of nearly 3 years, 262 neonates were found to have CH. The overall incidence of CH was 1 : 357 live births with a female/male ratio (F/M) of 1.4/1. Thyroid scan was performed on 116 (54%) of the infants with CH; of them, 33 cases (28.4%) were athyrotic (F/M = 0.8/1) while seven infants (6%) had ectopic thyroid (F/M = 1.3/1) and 76 cases (65.6%) had a normal thyroid scan (F/M = 1.5/1). Infants with the absence of thyroid in TS had significantly higher TSH value in comparison with those with ectopic or normal TS (116.3 +/- 109.64 vs. 108.10 +/- 62.92 or 55.35 +/- 48.26 mIU/l, respectively, P < 0.0001). Although not statistically different, the mean T4 level was higher in normal TS group than in ectopic and athyrotic groups (8.03 +/- 3.48 vs. 6.36 +/- 5.57 or 5.04 +/- 3 microg/dl, respectively, P = 0.09). We conclude that Tc-99m TS is a useful diagnostic tool for the initial investigation of suspected CH and considering the correlation of TS results with blood TSH levels, proper management and close monitoring of hypothyroid infants with severe hormonal alterations is necessary for the detection of thyroid agenesia.     

Congenital hypothyroidism. Therapeutic strategy at the early stage of treatment

The aim of this work was to determine the optimum dosage of L-thyroxine (L-T4) given to infants with congenital hypothyroidism (CH). Thirty seven hypothyroid infants diagnosed through the French screening programme for CH have been treated in our clinic. The study analysed the biochemical parameters (TSH, FT4, FT3) and the L-T4 doses during the first year of life. Treatment was started at 23 days of age (range: 13 to 37). A dose of 7.5 micrograms/kg/d of L-T4 was given at diagnosis. After 2 weeks of treatment, FT3 was normal and FT4 at the upper limit of the normal values. At that time, TSH plasma levels were normal (less than 6 micro UI/ml) in 47% of cases. After 1.7 month of treatment, 22% of patients had TSH levels greater than 10 micro UI/ml despite normal FT4 and FT3. This group of patients, despite being given an identical L-T4 dose, had a significantly lower FT4. They were not different from those who normalized TSH levels in terms of etiology, delayed bone maturation and levels of FT4 or FT3 at diagnosis. In conclusion, an initial dose of 7.5 micrograms/kg of L-T4 normalized FT4, FT3 and TSH in 80% of our patients. Twenty percent of patients seem to need more L-T4 to bring TSH levels back to normal at the end of the second month of treatment.     

Effective methimazole dose for childhood Graves' disease and use of free triiodothyronine combined with concurrent thyroid-stimulating hormone level to identify mild hyperthyroidism and delayed pituitary recovery

Appropriate methimazole dosing for initial treatment of childhood Graves' disease is uncertain. A retrospective chart review was performed on 5 to 17 year-old children treated for Graves' disease. Patients were divided into two groups depending on initial methimazole dosing: low-dose and high-dose regimens using <0.5 mg/kg/day and >0.5 mg/kg/day, respectively. The low-dose regimen was effective in 5/12 (42%) of patients and the high-dose regimen was effective in 27/33 (82%) of patients (p = 0.016). There was also a statistically significant dose/time interaction for levels of free thyroxine (T4) (p = 0.025). During treatment, 63.3% of diagnosable samples showed unambiguous hyperthyroidism or triiodothyronine (T3) toxicosis, 16.7% elevated free T3 with normal free T4 and T3 levels, indicating borderline hyperthyroidism, and 20% showed thyroid-stimulating hormone (TSH) suppression with normal or low levels of free T4 and free T3, indicating delayed recovery of pituitary TSH secretion. Free T3 levels combined with concurrent TSH levels permit differentiation of mild hyperthyroidism from delayed pituitary recovery.     

Congenital hypothyroidism with delayed rise in serum TSH missed on newborn screening

We report on a female patient with congenital hypothyroidism (CH) missed on a newborn screening test. She is now 10 years old with retarded development. The patient was born premature at 34 weeks of gestation with birth-weight of 1515 g, and was judged to be normal in the screening programme of Niigata Prefecture. However, she gradually suffered from poor weight gain and retarded development with stridor at breathing. Serum thyroid stimulating hormone (TSH) levels were rechecked and showed high values with normal T3 and T4 levels. She was referred to our hospital at the age of 13 months. She was diagnosed as having CH (ectopic thyroid) with a delayed rise in blood TSH concentration, probably due to the prematurity of the hypothalamic-pituitary-thyroid axis. l -thyroxine therapy brought a decline in TSH levels with partial improvement of her symptoms. Regardless of the result of newborn screening, infants with elevated serum TSH levels should be carefully examined for possible CH, even when T3, T4 and free T4 values are in the normal range.     

南京地区1998-2009年新生儿先天性甲状腺功能减低症筛查及治疗随访结果分析

目的 总结并分析1998年1月- 2009年12月南京地区新生儿先天性甲状腺功能减低症(CH)的筛查结果.方法 采集出生72 h新生儿442 454例的足跟血滴于滤纸上,采用时间分辨免疫法测定滤纸血斑促甲状腺激素(TSH),阳性者召回进一步测定静脉血TSH、三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、游离T3(FT3)、游离T4(FT4)以明确诊断.确诊者立即开始予左旋甲状腺素片(4.3～12.0μg·kg-1·d-1)替代治疗,定期监测其甲状腺功能,测量其身高、体质量,其中68例患儿子智力测试,以评估疗效.结果 12 a共筛查442 454人,确诊CH 183例,发病率为0.41‰,对117例进行随访.初始治疗时间的中位数为18 d(7～67d),初始左旋甲状腺素的平均剂量为7.35 μg·kg-1·d-1.CH患儿的身高、体质量结果基本达到正常参照标准.盖泽尔婴幼儿发展量表(GESELL)测试结果显示1例智能发育落后,8例智能发育迟缓.T4、FT4的治疗前水平与患儿的GESELL测试总分、适应性及精细运动均呈正相关(Pa＜0.05).结论 经筛查确诊的CH患儿,应尽可能早地进行激素替代治疗,可有效改善其预后.因此新生儿筛查及随访治疗工作值得推广和完善.     

Novel TSHbeta subunit gene mutation causing congenital central hypothyroidism in a newborn male

Newborn screening programs that use only high TSH levels as a marker for hypothyroidism may overlook neonates with congenital hypothyroidism (CH) due to TSH deficiency. We sought the cause of TSH deficiency in a neonate with low levels of thyroxine and TSH. The coding region of the TSHbeta gene was amplified and its sequence examined for mutations. Two mutations in exon 3 were identified: 1) a nucleotide deletion of T410 in codon 105 resulting in a frameshift in one allele, and 2) a previously unreported nucleotide deletion of T266 in codon 57, causing a frameshift and a premature stop at codon 62 in the other allele. We describe a compound heterozygous patient with TSHbeta mutations at codons 57 and 105 that interfered with a critical disulfide bond in the TSH molecule and caused CH. State screening programs that measure both T4 and TSH levels have the potential to detect newborns with congenital central hypothyroidism.     

Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down's syndrome

In order to delineate the spectrum of thyroid abnormalities in children with Down's syndrome (DS), first visit height data (SDS) and serum TSH, T4 and antiperoxidase antibodies concentrations were retrospectively evaluated in 137 children (71 girls) with DS (0.04-16 years). RESULTS: Congenital hypothyroidism was detected in 2.9% of patients. Thyroid disease occurred in 9%: four hyperthyroidism and eight hypothyroidism. Overt thyroid disease was always related to thyroid autoimmunity. The remaining 121 patients had normal T4 levels but increased mean TSH compared with controls (4.7 +/- 2.8 vs 2.3 +/- 1.3 mU/l). According to TSH levels, they were divided into two groups: G1 (n = 68) with normal TSH (<5 mU/l), and G2 (n = 53) with high TSH (> 5 mU/l). T4 levels were significantly lower in G2 (p < 0.01 vs G1 and controls). Height SDS was not different. CONCLUSIONS: Thyroid disorders are frequent in children with DS. Subtle thyroid abnormalities found in patients with DS with no evidence of clinical dysfunction need further investigation to demonstrate whether there is a need for therapeutic intervention.     

Newborn screening for congenital hypothyroidism

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.     

Euthyroid sick syndrome in children with acute viral hepatitis A.

According to the clinical findings, the activity of serum asparate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2) and the level of total bilirubin, 45 children with acute viral hepatitis A were divided into two groups: with mild and moderately severe degree of disease. By determining the products of the peripheral thyroxine metabolism-T3 and rT3, as well as the other thyroid parameters (T4, FT4, TSH and TBG) we have found significantly lower T3 level and significantly higher T4 and TBG levels in both groups of patients in comparison with control group. At the same time, the level of biologically less active rT3 was increased in patients with moderately severe form of disease, while no differences were found in the values of TSH between the ill and control patients. TRH induced TSH release was normal in all patients. The results of this study point to the development of euthyroid sick syndrome or low T3 syndrome in children with viral hepatitis A.     

Does Congenital Hypothyroidism Have Different Etiologies in Iran?

Objective

To determine the prevalence of congenital hypothyroidism (CH), permanent and transient CH.

Methods

From November 2006 to September 2007, 63031 newborns were screened by measuring serum TSH obtained by heel prick. The neonates who had a TSH≥5mU/L were recalled for measurement of serum T₄, thyroid stimulating hormone (TSH) and TSH receptor blocking antibodies (TRBAb) in venous samples. In 43 primarily diagnosed as cases of CH, treatment was discontinued at age 2–3 years for 4 weeks and T₄ and TSH were measured again. Permanent or transient CH was determined from the results of these tests and radiologic evaluation.

Findings

The incidence of congenital hypothyroidism was found to be 1:1465 with a female to male ratio of 1.19:1. The most common clinical findings were prolonged jaundice (73%), large anterior fontanel (56%) and wide posterior fontanel (55%). In 43 patients with CH, prevalence of permanent and transient form of the disorder was 53.6% and 46.4% respectively. Permanent CH was associated with higher initial TSH level than transient hypothyroidism (P<0.001). The most common etiology of permanent CH was dyshormonogenesis (57%). TRBAb was found in 6.8% of the total 43 cases.

Conclusion

Congenital hypothyroidism in Iran may have different etiologies. Due to higher rate of transient CH than other similar researches, it is reasonable to follow these patients for a longer period to rule out the possibility of permanent hypothyroidism.     

Linear growth in children with congenital hypothyroidism detected by neonatal screening and treated early: a longitudinal study

We performed a longitudinal study of a cohort of 74 children with congenital hypothyroidism (CH) detected by neonatal screening (Buenos Aires Province, Argentina) up to the age of 3 years old, in order to study linear growth and the relationship with the severity of CH at diagnosis. The mean age at diagnosis and the start of the treatment was 16.9 +/- 5.2 days. The patients were divided into group 1--severe CH (pretreatment T4 level <4 microg/dl) (n = 47)--and group 2--less severe CH (pretreatment T4 level > or = 4 microg/dl) (n = 27). Patients with CH treated early showed a sexually dimorphic pattern of growth: girls tended to be longer than boys at all ages. Boys showed some delay of growth during the first year. No difference was found in linear growth between the two groups (more/less severe CH). Height was normal in both sexes at the age of 3 years old.     

云南省部分地区先天性甲状腺功能减低症治疗效果分析

目的观察不同初始治疗剂量和治疗时机对先天性甲状腺功能减低症(CH)的疗效影响。方法以云南省4个地区新生儿筛查提示TSH异常、最终确诊并治疗随访的98例CH患儿为研究对象,予左旋甲状腺素钠治疗,按初始治疗剂量分为标准剂量组(每日10~15μg/kg)和小剂量组(每日10μg/kg),按照治疗起始时间又分为2月龄内治疗组和2月龄后治疗组。监测治疗前及治疗后多时点的甲状腺功能以及体格和神经发育情况。结果治疗后2周,标准剂量组的TSH低于小剂量组,FT4高于小剂量组,差异有统计学意义(P0.05),治疗后其他时间点的TSH、FT4差异均无统计学意义(P0.05);两组在治疗前以及治疗后各个时间点体格和神经发育的差异无统计学意义(P0.05)。不同治疗时机组,治疗后各个不同时间点的TSH和FT4及体格发育的差异均无统计学意义(P0.05);2月龄内开始治疗的患儿在6月龄时适应性行为、大运动、精细动作能区评分,12月龄时大运动能区评分,18月龄时精细动作能区评分,以及24月龄时语言能区评分均较高,差异具有统计学意义(P0.05)。结论标准剂量组疗效优于小剂量组,但需注意治疗后甲亢表现;治疗时机对CH患儿神经发育影响大,一经确诊,应尽早开始治疗。     

Quantitative computed tomography measurements of bone mineral density in prepubertal children with congenital hypothyroidism treated with L-thyroxine

Low bone density (BD) has been reported in patients with hyperthyroidism. Whether or not levothyroxine (LT4) therapy in children with congenital hypothyroidism (CH) affects BD is unclear. Medical records of 45 patients with various etiologies of CH who had at least one BD measurement (32 female, mean age 7.6 +/- 2.6 years) were reviewed. The mean LT4 dose was 3.6 +/- 0.88 microg/kg/day. Cancellous bone density (CaBD) was measured by quantitative computed tomography (CT) in all 45 patients and 20 had measurements of cortical bone density (CoBD), cross-sectional area (CSA) and cortical bone area (CBA) of the femur. TSH levels were considered partially or completely suppressed when values were <1.0 or <0.5 microIU/ml, respectively. The control group consisted of age- and gender-matched healthy children. No significant differences were found in CaBD, CoBD, CSA, or CBA between patients with CH and controls. There were no significant differences between initial and subsequent BD measurements. No correlations were found between CaBD and etiology of CH, dose or duration of LT4 therapy, or serum TSH. In pre-pubertal children with CH, LT4 appears to have no significant effect on BD. Moreover, absence or hypoplasia of the thyroid parenchyma appears to have no significant impact on bone formation within the first 10 years of life.     

Thyroid dysfunction in Down syndrome

We investigated the thyroid function of 151 patients with Down syndrome. Compared with a control group of 89 siblings nearest in age to their brother or sister with Down syndrome, the mean thyroid-stimulating hormone (TSH) value was significantly higher in patients with Down syndrome than in subjects without Down syndrome. However, the mean thyroxine (T4) levels in both groups were nearly the same. In the Down syndrome group there was a trend for TSH values to increase and for T4 values to decrease with advancing age. Of the 151 patients with Down syndrome, ten had both significantly elevated TSH levels (greater than or equal to 9.5 microU/mL) and significantly decreased T4 levels (less than or equal to 5.5 micrograms/dL), 21 had only abnormally high TSH values, seven had only markedly increased T4 levels (greater than or equal to 12.0 micrograms/dL), and three had only significantly decreased T4 levels. The intellectual function of patients with both abnormal TSH and T4 levels was significantly lower (mean IQ, 41.7) than that of Down syndrome patients with only increased TSH values (mean IQ, 53.8) and that of Down syndrome patients with normal thyroid function (mean IQ, 55.3). This study provides further evidence that there is an increased prevalence of thyroid dysfunction in patients with Down syndrome.     

1型糖尿病并低三碘甲状腺氨酸综合征201例

目的探讨1型糖尿病(T1DM)及糖尿病酮症酸中毒(DKA)患儿并低三碘甲状腺氨酸(T3)综合征的临床特点。方法采用放射免疫分析法检测91例T1DM并DKA患儿(DKA组)及110例单纯T1DM患儿(非DKA组)血清T3、甲状腺素(T4)、促甲状腺激素(TSH)水平,观察2组T3、T4下降例数及水平,并将DKA组分为轻、中、重3个亚组,观察不同组别中甲状腺激素变化特点。结果 DKA组易发生T3、T4下降,DKA组T3[(0.54±0.51)μg.L-1]、T4[(5.65±2.80)μg.L-1]与非DKA组T3[(1.02±0.38)μg.L-1]、T4[(9.28±2.85)μg.L-1]比较,差异均有统计学意义(Pa<0.000 1)。中、重度DKA组与非DKA组T3比较,差异有统计学意义(Pa<0.000 1),轻、中、重度DKA组与非DKA组T4比较,差异均有统计学意义(Pa<0.000 4,0.000 1)。DKA组与非DKA组TSH比较,差异无统计学意义(P>0.05)。结论 T1DM患儿甲状腺激素检测的结果主要表现为T3降低,部分伴T4降低,其疾病的严重程度与甲状腺激素降低程度一致,T1DM并DKA患儿的T3、T4水平均有明显下降,提示T1DM患儿需重视甲状腺激素的检测,利于早期防治。     

Congenital hypothyroidism in a child with unsuspected familial dysalbuminemic hyperthyroxinemia caused by a mutation (R218H) in the human albumin gene.

We found familial dysalbuminemic hyperthyroxinemia (FDH) in a 5-month-old boy with congenital hypothyroidism (CH) who had a blood thyrotropin (TSH) level of 479 mU/L but normal total serum thyroxine (T4) and higher than normal total triiodothyronine (T3) levels. Thyroid hormone substitution began at 5 weeks of age when T4 and T3 concentrations were below normal. Until the age of 5 months, treatment with levothyroxine was suboptimal on the basis of high serum TSH levels despite above-normal T4 levels. FDH was confirmed by isoelectric focusing and testing of other family members. DNA analysis of the patient revealed R218H, a mutation in the serum albumin gene associated with FDH, which was also present in the patient's euthyroid father and brother. Thyroid scans, serum thyroglobulin measurements, and free T4 measurements using equilibrium dialysis or 2-step immunoassay methods can identify thyroid hormone-binding protein defects and simplify the diagnosis and treatment of infants with CH.