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.     

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.     

Changes in the cAMP synthesis by fetal thyroid during the 5 last days of the intrauterine life in the rat

The cAMP synthesis by fetal rat thyroids is stimulated in vitro by thyrotropin (TSH) or forskolin during the 5 last days of intrauterine life. The effects are TSH- or forskolin-dose-dependent with equal responses to 20 mIU.ml-1 TSH or to 1 microM forskolin. The magnitude of the responses to TSH or to forskolin decreases significantly as the fetus is ageing. Since forskolin effects bypass hormone receptors, the adenylate cyclase activity can be concluded to decrease during the end of gestation probably in relation with thyroid iodine accumulation. The responses to TSH and forskolin becoming synergic between 19 1/2 and 21 1/2 days indicate modifications of adenylate cyclase properties probably related to some maturation of the enzyme.     

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.     

Receptor-mediated cAMP production in adult and infant ferret tracheal epithelium.

Tracheal epithelial cells obtained from adult and infant ferrets were grown in primary culture in vitro. Cells from adult animals grew readily, and many ciliated cells were observed in the cultures. Successful cultures were derived from infant animals, but cell number in infant and adult cultures began to decrease after 6 d. Receptor-mediated activation of adenylate cyclase was determined by incubating monolayers of adult or neonatal cells with beta-adrenergic agonists, prostaglandin E2 (PGE2) and vasoactive intestinal peptide and measuring cAMP production. beta-adrenergic agonists and PGE2, but not vasoactive intestinal peptide, stimulated production of cAMP in both cell types. The 50% effective concentration for isoproterenol and PGE2 in neonatal ferret tracheal epithelial (NFTE) cells was nearly 10-fold more than for adult ferret tracheal epithelial (FTE) cells, but maximal agonist-stimulated cAMP production was significantly different between the cell types only for PGE2. Radioligand binding studies were performed using the beta-adrenergic antagonist [125I]iodocyanopindolol on membrane particulates from confluent monolayers and freshly isolated FTE cells. Binding of iodocyanopindolol was saturable, stereoselective, and of high affinity (binding affinity = 26.1 +/- 6.6 pmol/L, adult; 16.5 +/- 5.7 pmol/L, NFTE). Competition studies with the specific beta 2-adrenergic receptor antagonist, ICI 118 551 revealed a predominance of beta 2-adrenergic receptors on both adult FTE and NFTE cells. Receptor density was significantly higher in adult FTE compared with NFTE cells (48.2 +/- 9.1, 18.1 +/- 1.5 fmol/mg, respectively). Basal adenylate cyclase activity was significantly lower in neonatal cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative in vitro myocardial inotropic effects and in vivo hemodynamic effects of forskolin and isoproterenol in young lambs

Previous studies have shown a decreased responsiveness of young lambs to isoproterenol, a beta-adrenergic agonist, when compared to older lambs. To see if this decreased responsiveness of immature lambs is secondary to an abnormality of the beta-adrenergic receptor/adenylate cyclase complex, we compared the effects of isoproterenol to forskolin, a direct activator of the catalytic subunit of adenylate cyclase. In isometrically contracting right ventricular trabeculae from five lambs (5-13 d old), the maximal developed tension with isoproterenol (875 +/- 84 mg, mean +/- SD) and forskolin (704 +/- 189 mg) was similar. However, the median effective dose for isoproterenol (5.3 +/- 3.4 X 10(-7) M) was significantly less than the minimal median effective dose for forskolin (2.5 +/- 1.3 X 10(-6) M) indicating a lesser sensitivity to forskolin. In eight conscious resting lambs (4-13 d old) we measured the hemodynamic response to graded infusions of isoproterenol and forskolin. At maximal dosage, the increase in cardiac output was significantly greater with isoproterenol (+130%) than forskolin (+55%). Heart rate also increased more with isoproterenol than forskolin. These data show that direct stimulation of adenylate cyclase in young lambs does not provide better inotropic or chronotropic responses than beta-adrenergic stimulation with isoproterenol. This suggests that the decreased beta-adrenergic responsiveness in newborn lambs is secondary to abnormalities that exist beyond the level of the beta-adrenergic receptor/adenylate cyclase complex.     

先天性甲状腺功能低下症对新生儿左心功能的影响

目的　评价先天性甲状腺功能低下症 (CH)新生儿的左心收缩和舒张功能变化 ,并探讨其与血甲状腺激素水平的相关性。方法　对 35例确诊为CH的新生儿和 30例正常新生儿进行超声心动图检查 ,分别用M型超声心动图测量左室射血分数 (LVEF)、左室短轴缩短率 (LVFS) ;脉冲多普勒 (PWD)测量二尖瓣口血流舒张早期峰值速度 (Em)、二尖瓣口血流舒张晚期峰值速度 (A m) ;定量组织速度成像 (QTVI)测量二尖瓣环收缩期运动峰值速度 (sm)、二尖瓣环舒张早期运动峰值速度 (em)、二尖瓣环舒张晚期运动峰值速度 (am) ;组织追踪显像 (TTI)测量收缩期二尖瓣环下移距离 (MAD) ,并对血甲状腺激素水平和心功能指标行相关性分析。结果　两组间收缩功能指标LVEF、LVFS、sm、MAD及舒张功能指标Am、Em/Am、、em/am、、Em、em 差异均有显著性意义 (P <0 0 5 ) ,其中两组间MAD、sm、Em、em 差异有极显著性意义 (P <0 0 0 1)。心脏收缩功能指标LVEF、sm、MAD及舒张功能指标Em、Am、em、em/am 与TT3 、TT4呈正相关 (P <0 0 5 ) ,与TSH呈负相关 (P <0 0 5 ) ,MAD、sm、Em、em 与血TT4、TSH水平的相关性最好 (P <0 0 0 1)。结论　先天性甲状腺功能低下症新生儿常伴有左心收缩和舒张功能下降 ,血甲状腺激素水平可直接影响左心功能 ,QTVI     

The beta adrenergic system of lymphocytes in children with atopic dermatitis

A defect in the beta-adrenergic system is considered to be one of the basal causes of atopic dermatitis (AD). The number and affinity (KD) of beta-receptors was determined in lymphocytes of 19 children with AD and of 17 controls using the radioligand 125JCYP to find out whether this hypothesis is relevant. In addition, the basal cAMP level was measured as well as the cAMP-accumulation after stimulation of the adenylcyclase (AC) via the beta-receptor with 10(-4) M isoprenaline (IPN) and after direct stimulation of AC with 10(-4) M forskolin. Receptor quality and receptor quantity were compared to the severity of AD. A statistically significant difference between AD and control children was not registered for the following parameters: receptor-density, affinity for 125ICYP, cAMP-accumulation after adenylcyclase stimulation via the beta-receptor with IPN or after direct stimulation with forskolin. The increase in cAMP after IPN or forskolin was in the same range for children suffering from AD as for controls. Only the basal cAMP was significantly lower. Three patients with very severe AD (greater than 20% body surface area) had a significantly reduced number of beta-receptors (603 +/- 123 BS/Ly) compared with the control group (1142 +/- 112 BS/Ly). A linear relation existed between age, receptor density and isoprenaline-mediated cAMP accumulation for both control children and those with AD. This age-dependent response of the beta-receptor seems to be specific as cAMP-accumulation after stimulation with forskolin was not age-related.     

定量组织速度成像和组织追踪显像技术评价先天性甲状腺功能减退症新生儿的右心功能

目的应用定量组织速度成像（QTVI）和组织追踪显像（TTI）技术评价先天性甲状腺功能减退症（CH）新生儿在甲状腺素替代治疗前后的右心功能变化,并探讨其临床应用价值。方法应用QTVI和TTI技术离线分析35例正常新生儿以及52例CH新生儿在左旋甲状腺素（L-T4）替代治疗前与治疗1个月后的心尖四腔切面三尖瓣环运动速度曲线和位移曲线,测量收缩期峰值速度（Vs）、收缩期最大位移（D）、舒张早期峰值速度（Ve）、舒张晚期峰值速度（Va）,计算Ve／Va值;常规记录三尖瓣口脉冲多普勒（PWD）血流频谱,测量舒张早期充盈峰值速度（E）,舒张晚期充盈峰值速度（A）,计算E／A值。同时运用化学发光法检测各组患儿的血清促甲状腺素、三碘甲状腺原氨酸总量、甲状腺素总量、游离三碘甲状腺原氨酸和游离甲状腺素水平,并与QTVI、TTI检测指标行Person相关分析。结果CH组新生儿E峰及E／A值低于对照组（均P〈0．001）,但A峰差异无统计学意义（P〉0．05）;QTVI及TTI示,CH组Ve、Ve／Va值、Vs及D均显著低于对照组,差异有统计学意义（均P〈0．001）,而Va差异无统计学意义（P〉0．05）。经L-T4替代治疗后1个月,CH组新生儿Ve、Ve／Va值、Vs、D及E、E／A值分别为（6．92±1．86）cm／s、（1．13±0．22）、（5．92±1．03）cm／s、（0．78±0．17）cm和（61±10）cm／s、（1．1±0．4）,与治疗前比较差异有统计学意义（均P〈0．001）。相关分析显示,Ve、Ve／Va值、Vs、D与三碘甲状腺原氨酸总量、甲状腺素总量TT4、游离三碘甲状腺原氨酸、游离甲状腺素呈显著正相关（均P〈0．01）,与促甲状腺素呈显著负相关（均P〈0．01）。结论CH新生儿的右心收缩与舒张功能均显著低于正常新生儿,早期及时甲状腺素替代治疗可逆转受损的右心功能。应用QTVI及TTI技术检测三尖瓣环运动频谱可定量、准确、有效地评价新生儿右心功能。     

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。     

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 function tests in the newborn infants of preeclamptic women.

The purpose of this study was to identify possible changes in thyroid functions in newborn infants of preeclamptic women. Fifteen neonates (nine boys and six girls) of preeclamptic women and 17 healthy neonates (nine boys and eight girls) for the control group were included in the study. Serum thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and total thyroxine (TT4) levels and thyroid gland volumes were determined in both groups. Serum TSH and TT4 levels were not statistically different between the two groups. However, serum TT3 level was 79.22 +/- 40.19 ng/dl in the study group and 40.00 +/- 15.99 ng/dl in control subjects (p < 0.01). The mean right, left and total thyroid volumes were 1.3 +/- 1.2 ml, 1.2 +/- 1.1 ml and 2.4 +/- 2.3 ml in the study group and 0.6 +/- 0.2 ml, 0.6 +/- 0.2 ml, and 1.1 +/- 0.4 ml in the control group, respectively (p < 0.05). The mean thyroid volume/body weight was 0.9 +/- 0.09 ml/kg in the study group and 0.3 +/- 0.06 ml/kg in the control group (p < 0.05). In conclusion, we would like to stress that preeclampsia might be a cause of fetal and neonatal thyroid enlargement and elevated serum TT3 level.     

Persistently raised thyroid stimulating hormone in adequately treated congenital hypothyroidism on long-term follow-up

AIM: To determine the percentage of patients with inappropriate secretion of TSH (ISTSH) in a large cohort of patients with congenital hypothyroidism (CH), and to examine a probable influence of the pretreatment T4 or TSH levels and the etiology of CH on ISTSH by describing the clinical features of these patients. PATIENTS AND METHODS: We retrospectively examined the records, including anthropometric data, clinical findings, and thyroid function tests (TFT), of 500 children diagnosed with CH. Inclusion criteria of ISTSH were appropriate doses of L-T4, improvement of clinical findings, normalization of serum total T4 levels and persistently high TSH concentrations. A group of patients who demonstrated adequate suppression of TSH (<6 mU/l) with therapy among 500 CH patients were chosen randomly as a control group. Both groups were compared with regard to the etiology of CH, and TFT at baseline and during the treatment period. RESULTS: Overall, 27 (5.4%) out of the 500 patients with CH had ISTSH. Nine patients (1.8%) with ISTHS did not show TSH normalization during the follow-up period. Four out of 27 patients with ISTSH had organic lesions (three empty sella, one corpus callosum agenesis) on cranial imaging. No statistically significant difference was found between the groups for etiological classification. The pretreatment T4 and TSH levels in ISTHS and control groups were not significantly different. CONCLUSIONS: Our results suggest that a minority (5.4%) of adequately treated children with CH have persistently raised TSH levels. The delay in normalization of TSH is not related to pretreatment T4 and TSH values or the etiology of CH.     

Ontogeny of beta-adrenergic receptors in the rat lung: effects of hypothyroidism

Beta-Adrenergic receptors were identified in membrane fractions of rat lung with the beta-adrenergic antagonists (-)-[3H]-dihydroalprenolol (-)-[3H]DHA) and (+/-)-[125I]-iodohydroxybenzylpindolol ((+/-)-[125I]HYP). Binding capacity (Bmax) for (-)-[3H]DHA increased progressively from 46 +/- 7 on day 18 of gestation to 510 +/- 70 femtomoles . mg-1 protein (mean +/- S.D.) on postnatal day 28, at which time adult Bmax was attained. An increase in (-)-[3H]DHA binding capacity of the lung was observed between postnatal days 15 and 28, during the known period of increased thyroid gland secretory activity, serum triiodothyronine (T3), and thyroxine (T4) concentrations in the rat. We therefore studied lung beta-adrenergic receptors in rat pups made hypothyroid with propylthiouracil (PTU) (in utero and postnatally) compared to normal age-matched control pups and to euthyroid pups which were treated with PTU but were also injected daily with thyroxine (T4-treated). Hypothyroid pups grew nearly normally until postnatal day 15 but grew poorly thereafter; but day 28 somatic and lung weight, lung DNA, and protein were markedly decreased in hypothyroid pups as compared to controls. Pulmonary beta-adrenergic receptors were similar in hypothyroid pups and controls on day 15, but were markedly decreased in hypothyroid pups on day 28 (294 +/- 57 versus 489 +/- 82 femtomoles . mg-1 protein in T4 treated euthyroid controls). Treatment of the hypothyroid pups with T4 on day 25 significantly increased lung beta-adrenergic receptors to near normal concentrations by day 28. We conclude that thyroid hormones or thyroid dependent factors enhance pulmonary beta-adrenergic receptor synthesis and that thyroid hormone is required for the normal postnatal maturation of the beta-adrenergic receptor system in the rat lung.     

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.     

Normal thyroid function in young adults who were born very preterm

There is some evidence for elevated thyrotropin (TSH) levels in children born preterm, but follow-up studies into adulthood are lacking. We tested whether thyroid function in young adults born at a gestational age < 32 weeks, with either an appropriate (appropriate for gestational age, AGA) or low birth weight for gestational age (small for gestational age, SGA), differed from that in age-matched controls. We made our measurements when the study participants reached 21 years of age. Serum concentrations of TSH and free T4 (fT4) and body composition were measured in subjects born preterm and AGA (n = 29) or SGA (n = 28), and in non-preterm controls (n = 30). The TSH and fT4 concentrations of participants were within normal limits. Free T4 levels in subjects born preterm were slightly higher than those in controls: 17.0 +/- 2.4 (AGA) and 17.2 +/- 1.7 (SGA) vs. 16.1 +/- 1.9 pmo/L (p = 0.04). TSH concentrations did not differ between groups. From these preliminary data, we conclude that young adults born preterm have a normal thyroid function.     

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.     

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.     

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.