Cord blood thyroid stimulating hormone level — interpretation in light of perinatal factors

Objectives

To study the influence of perinatal factors on cord blood TSH (CB TSH) levels.

Design

Cross-sectional study.

Setting

Tertiary care private hospital.

Methods

CB TSH levels were measured in 952 live-born infants using electrochemiluminescence immunoassay. The effect of perinatal factors on the CB TSH levels was analyzed statistically.

Results

The median CB-TSH was 8.75 microIU/mL (IQR = 6.475–12.82) with 11.5% neonates having values more than 20. CB TSH was significantly raised in first order neonates (P <0.01) and in babies delivered by assisted vaginal delivery and normal delivery (P <0.01). Neonates who had fetal distress or nonprogress of labour had significantly higher CB TSH than those who were delivered by elective caesarean section. Requirement of resuscitation beyond the initial steps and low Apgar scores at 1 minute also resulted in significantly raised CB TSH (both P <0.01). Maternal hypothyroidism, maternal hypertension and neonates’ weight appropriateness for gestation, gestational age and birth weight did not have significant effect.

Conclusions

The incidence of high cord blood TSH (>20 microU/mL) is 11.45%. On multivariate analysis, requirement of resuscitation, mode of delivery and fetal distress as indication for LSCS were significant factors affecting CB TSH values. Hence, these values need to be interpreted in light of perinatal factors.     

Cord blood thyroid‐stimulating hormone and free T4 levels in Turkish neonates: Is iodine deficiency still a continuing problem?

Background: The objectives of this study were to determine the cord blood thyroid‐stimulating hormone (TSH) and free T₄ (FT₄) levels in Turkish neonates and to determine whether these variables reveal iodine deficiency. Methods: We collected 818 cords from healthy mothers at parturition and measured levels of FT₄ and TSH. We also measured cord blood FT₄ and TSH levels in different stages of gestation and gender. We grouped the neonates according to cord serum TSH levels, either being less (Group A) or greater (Group B) than 10 mIU/L. Group A included 589 neonates (300 girls [51%] and 289 boys [49%]) and Group B included 229 neonates (105 girls [45%] and 124 boys [55%]). Results: The percentage of subjects with cord blood TSH < 10 mIU/L and >10 mIU/L was 72% and 28%, respectively. Although cord TSH levels in Group B were greater than those in Group A (P < 0.001), cord blood FT₄ levels in Group B were lower than those in Group A (P < 0.05). There was no difference between both sex in terms of birthweight and maternal age. TSH and FT₄ levels did not vary according to neonate sex during gestation, except for from week 37 to 41. TSH levels of male neonates at the 41st week of gestation were higher than those of female neonates (P < 0.05). There were no effects of birthweight on TSH and FT₄ levels if the neonate was lighter than 2500 g at birth. TSH levels of male neonates were higher than those of female neonates when their birthweights were <2500 g (P < 0.05). There was no significant difference in TSH levels according to birthweights in male neonates. Conclusion: Our data provide the normative data for cord blood TSH and FT₄ levels in Turkish neonates and show that iodine deficiency is a still a public health problem in Turkey. These measurements can be useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism as well as evaluation of the success of the iodination program.     

The Influence of Labor and Delivery on Preterm Fetal Adrenal Function

ABSTRACT. The influence of labor and route of delivery upon umbilical cord serum levels of Cortisol and dehydroepiandrosterone sulfate in one hundred sixty-nine preterm infants not exposed prena-tally to corticosteroids was studied. Vaginally born infants (group A, n=89) presented a higher mean cord Cortisol and dehydroepiandrosterone sulfate concentrations than those delivered by cesarean section (group B, n=80). Although there were no differences in Cortisol and dehydroepiandrosterone sulfate levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I, n=42) and those without labor (group B-II, n=38), the mean Cortisol and dehydroepiandrosterone sulfate concentrations were higher in group A than in group B-I. There was a correlation between umbilical cord Cortisol and dehydroepiandrosterone sulfate levels. It is concluded that there is no association between the presence of labor and high cord serum levels of Cortisol and dehydroepiandrosterone sulfate and there is an association between vaginal delivery and high cord Cortisol and dehydroepiandrosterone sulfate levels in preterm infants. It is suggested that the stress of vaginal delivery stimulates the secretion of fetal Cortisol and dehydroepiandrosterone sulfate in preterm infants.     

The influence of labor and delivery on preterm fetal adrenal function

The influence of labor and route of delivery upon umbilical cord serum levels of cortisol and dehydroepiandrosterone sulfate in one hundred sixty-nine preterm infants not exposed prenatally to corticosteroids was studied. Vaginally born infants (group A, n = 89) presented a higher mean cord cortisol and dehydroepiandrosterone sulfate concentrations than those delivered by cesarean section (group B, n = 80). Although there were no differences in cortisol and dehydroepiandrosterone sulfate levels between infants delivered by cesarean section after spontaneous onset of labor (group B-I, n = 42) and those without labor (group B-II, n = 38), the mean cortisol and dehydroepiandrosterone sulfate concentrations were higher in group A than in group B-I. There was a correlation between umbilical cord cortisol and dehydroepiandrosterone sulfate levels. It is concluded that there is no association between the presence of labor and high cord serum levels of cortisol and dehydroepiandrosterone sulfate and there is an association between vaginal delivery and high cord cortisol and dehydroepiandrosterone sulfate levels in preterm infants. It is suggested that the stress of vaginal delivery stimulates the secretion of fetal cortisol and dehydroepiandrosterone sulfate in preterm infants.     

BREAST MILK THYROXINE AND NOT COW'S MILK MAY MITIGATE AND DELAY THE CLINICAL PICTURE OF NEONATAL HYPOTHYROIDISM

Abstract. Sack, J., Frucht, H., Amado, O., Brish, M. and Lunenfeld, B. (Institute of Endocrinology, the Chaim Sheba Medical Center, Tel Hashomer, Israel). Breast milk thyroxine and not cow's milk may mitigate and delay the clinical picture of neonatal hypothyroidism. Acta Paediatr Scand, Suppl. 277: 54, 1979.-Thyroxine concentration was measured in human milk and Cow's milk products by a specific radioimmunoassay. The mean (± S.E.M.) milk T4 concentration during the first 5 days postpartum was 0.7±0.3 µg/dl (n=11). The mean T4 concentration between 6–49 days postpartum rose to 3.1±0.2 µg/dl (n=108), falling after 50 days to a mean of 1.4±0.2 µg/dl (n=39). The mean (± S.E.M.) T3 concentration in breast milk in the first 50 days postpartum was 386±17 ng/dl (n=56). T4 concentration in cow's milk products was less than 0.3 µg/dl. Thyroxine concentration in 24 hours breast milk collection ranged from 0.7 to 7.7 µg/dl and the total T4 in this milk ranged from 0.7 to 28 µg/day. These data suggest that milk of human but not bovine origin may provide a significant exogenous source of T4 to the premature infant. This amount of exogenous T4 which is insufficient in preventing the proceeding of neonatal hypothyroidism, may delay the clinical recognition of this disorder. This once again emphasizes the importance of early screening for neonatal hypothyroidism.     

Investigation of the relationship between low Apgar scores and early neonatal thyroid function

BACKGROUND: The aim of the present study was to assess the effects of low Apgar scores on perinatal thyroid function. METHODS: Forty full-term infants delivered by the normal spontaneous vaginal route were enrolled into the study. All babies had 1 and 5 min Apgar scores below 4. The control group consisted of 26 full-term healthy neonates. Cord blood and serum tri-iodothyronine (T3), thyroxine (T4), reverse tri-iodothyronine (rT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) and thyroid-binding globulin (TBG) determinations were performed by an enzyme immunoassay method. RESULTS: The mean values of FT4 and T4 observed in the cord blood of the study group were significantly lower compared with matched controls, whereas the mean TSH values were significantly higher. There were no differences in concentrations of T3, rT3 and TBG between the two groups. CONCLUSIONS: These results demonstrate the existence of transient hypothyroidism at birth in babies with Apgar scores below 4 delivered by the spontaneous vaginal route.     

Bone γ-Carboxyglutamic Acid Containing Protein in the Perinatal Period

ABSTRACT. We measured bone γ-carboxyglutamic acid-containing protein (BGP), calcium (Ca), phosphorus (P), and alkaline phosphatase (Al-P) in paired maternal and cord sera, and urinary γ-carboxyglutamic acid (γ-GIa) in neonates. The circulating BGP was 41.21±2.47 ng/ml and 7.44±0.87 ng/ml in the cord (n=15) and the maternal (n=14) sera, respectively. The urinary γ-GIa in the neonates was 147.68 ± 10.75 μ.mol/g creatinine (n=15). The cord serum BGP was significantly higher than the normal adult level. The maternal serum BGP was at the same level as in other adults. It is conceivable that the fetus may produce BGP during gestation, as the cord serum BGP level was significantly higher than the maternal level and there was no correlation between the cord and maternal serum BGP concentrations. The reason for the elevated circulating BGP level in the cord serum is not known, but increased bone turnover may be a factor. The cord serum BGP may include not only carboxylated but also non-γ-carboxylated BGP because of fetal vitamin K deficiency.     

Recovery Period of Hypersecretion of Thyroid-Stimulating Hormone in Patients with Congenital Hypothyroidism Treated with Thyroid Hormone

The recovery periods of serum thyroid stimulating hormone (TSH) were studied in patients with congenital hypothyroidism found on neonatal screening. L-T4 was administered at 37.8 ± 15.1 days of age (M ± SD), and serum T4, T3, and TSH concentrations were measured. After L-T4 therapy with 10 µg/kg, the serum TSH levels decreased to below 10 µU/ml in five patients within a week, and in another two patients, within two weeks, and in the total number of 12 patients out of 15 (80%), by one month. These results suggest that the recovery of serum TSH occurs rapidly in hypothyroid infants. Thus, the serum TSH concentration may be a good measurement for assessing the adequacy of thyroid hormone therapy from early infancy in patients with congenital hypothyroidism.     

Relationship between serum leptin and thyroid hormones in children

BACKGROUND: Because leptin decreases food intake and increases energy expenditure, the possible influence of thyroid status on the leptin system has been investigated mainly in adults and animals. However, the data available at present are very confusing. The aim of the present study was to assess the possible interaction of thyroid hormones with the leptin system. METHODS: Serum free thyroxine (FT4), a biologically active thyroid hormone, and thyroid stimulating hormone (TSH), a sensitive and reliable index of thyroid status, were examined in 51 children (19 males, 32 females) with mass screening-detected congenital hypothyroidism on continuous L-thyroxine (L-T4) substitution therapy. The subjects were divided into younger (n = 35, aged 1 month-5 years) and older (n = 16, 6 years-11 years) children groups. Serum levels of leptin and thyroid hormones were measured in the subjects. Body mass index (BMI) was estimated by the formula bodyweight (kg)/height x height (m2), which is known as the Kaup index in younger children and BMI in older children and adults. RESULTS: In the younger children group, serum leptin levels showed no correlation with serum TSH, FT4 or T4. In the older children group, serum leptin concentrations significantly correlated with T4 (r = 0.510, P < 0.05) and BMI (n = 16, r = 0.647, P < 0.01), but not with TSH or FT4. CONCLUSION: The role of thyroid hormones in modulating leptin synthesis and secretion seems to have little, if any, clinical or biological relevance.     

Predictors of AVP and TSH levels and the timing of first voiding in the newborn

To evaluate obstetric predictors of umbilical cord plasma AVP levels, serum TSH levels and the timing of first voiding, 87 singleton term newborns were divided into three groups: group A, vaginal delivery (n = 30); group B, cesarean section (CS) during labor (n = 26); and group C, elective CS (n = 31). The AVP concentration was 120 (0.7-2170) ng/L in group A, 1.8 (0.01-183) ng/L in group B, and 0.8 (0.01-30) ng/L in group C (p < 0.001). In group A, the TSH concentration was 10.20 (3.5-30.80) mU/L; in group B, 5.40 (2.10-43.00) mU/L; and in group C, 5.30 (2.90-11.00) mU/L (p = 0.001). Duration of labor had a positive correlation with AVP (p < 0.001) and TSH (p = 0.001) concentrations. The timing of first voiding had a positive correlation with gestational age (p = 0.003), volume of additional feeding before first voiding (p < 0.001), and umbilical AVP concentration (p = 0.023). The AVP and TSH concentrations are associated with mode of delivery and duration of labor and AVP levels also with the timing of first voiding in the newborn.     

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.     

Direct assay of free thyroxine in children. Application to the monitoring of the treatment of hypothyroidism

A direct measurement of free thyroxine (FT4) by a radio-immunologic method using an analogue of thyroxine as tracer allowed to establish the normal values in 341 children from birth to puberty. These values were used as reference for the determination of free T4 in the diagnosis and management of treatment for congenital hypothyroidism. In 44 treated hypothyroid children, there was a positive correlation between the serum concentration of free T4 and the amount of levothyroxine given daily (r = 0.46, p less than 0.01). There was also a negative correlation between free T4 and serum TSH (r = 0.59, p less than 0.001). Thus, the measurement of free thyroxine seems to be a more reliable, more accurate and more sensitive parameter than that of total thyroxine or TSH for controlling the treatment of congenital hypothyroidism.     

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.     

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.     

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.     

不同出生体质量、性别新生儿脐血黄体生成素、卵泡刺激素、睾酮的水平变化

目的探讨脐血黄体生成素（LH）．卵泡刺激素（FSH）和睾酮（T）在不同出生体质量、性别新生儿脐血中的差异及其对胎儿生长发育的影响。方法根据新生儿出生体质量分为3组，其中巨大儿组28例，官内发育迟缓儿（IUGR）组31例；正常新生儿组71例。采用放射免疫分析法检测3组新生儿脐血LH,FSH和T水平。结果1．男性新生儿脐血LH、FSH和T水平均显著高于女性者（P〈0．001，0．05）；2．IUGR组脐血LH水平显著高于正常新生儿组（P〈0．05），而FSH水平显著低于正常组（P〈0．01）。结论脐血LH、FSH和T水平与胎儿性别有相关性，脐血LH与IUGR的发生有关。     

甲状腺激素对大鼠瘦素水平的影响(英文)

目的：下丘脑-垂体-甲状腺轴可能影响瘦素的分泌和代谢。该研究探讨甲状腺功能减低和甲状腺功能亢进时甲状腺激素对血清瘦素水平和脂肪瘦素mRNA水平的影响。方法：应用他巴唑和优甲乐人工造成大鼠甲状腺功能减低和甲状腺功能亢进状态,分别于用药10天、停药10天检测用药组、停药组和正常对照大鼠血清瘦素、T3、T4、TSH浓度、体重和脂肪瘦素的mRNA水平。结果：甲减用药组、甲亢用药组和正常对照组大鼠血清瘦素与体重均有相关性(P<0.05),相关系数分别0.84、0.83、0.94。去除体重因素,甲亢用药组、停药组血清瘦素和脂肪瘦素mRNA水平和正常对照组相比无明显差别(P>0.05),而甲减用药组血清瘦素(0.68±0.07 ng/ml)和脂肪瘦素mRNA水平(0.39±0.02)显著低于停药组(1.98±0.09 ng/ml)(0.87±0.05)和正常对照组(2.14±0.46 ng/ml)(0.95±0.03)(P<0.05)。结论：甲状腺素可能对血清瘦素的稳定分泌起一定的作用。［中国当代儿科杂志,2004, 6(5): 369-372］     

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.     

先天性甲状腺功能减退症新生儿心电图改变的意义

目的评价先天性甲状腺功能减退症(CH)新生儿的心电图(ECG)改变,及与血清甲状腺激素(TH)水平的相关性,探讨TH减少对新生儿心脏电生理活动的影响。方法对50例CH新生儿(日龄17～28d)和35例健康新生儿(健康对照组)进行常规十二导联ECG检查,分别检测心率(HR)、PR间期(PR)、QT间期(QT)、QRS波电轴(QRSa)、QRS波时限(QRS)、校正QT间期(QTC)等,同时用化学发光法测定血清游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、总三碘甲状腺原氨酸(TT3)、总甲状腺素(TT4)和促甲状腺素(FSH)水平,对心电图指标和血TH水平行相关性分析。结果与健康对照组相比,CH组血清FT3、FT4、TT3、TT4水平显著降低,TSH水平显著升高(Pa<0.001);CH组HR显著低于健康对照组,PR及QT较健康对照组显著延长(Pa<0.05),但二组QRSa、QRS及QTC差异均无统计学意义(Pa>0.05)。HR与FT3、FT4呈显著正相关,与TSH呈显著负相关(Pa<0.05);PR间期与FT3、FT4、TT4呈显著负相关,与TSH呈显著正相关(Pa<0.05);但QT、QRS、QRSa及QTC与血TH水平均无明显相关(Pa>0.05)。结论CH可对新生儿窦房结起搏产生显著影响,引起心脏自律性改变,而心肌动作电位、房室传导等电生理活动则尚未受影响。