School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement.

OBJECTIVE: To determine the feasibility of annual hypothyroid screening of children with Down's syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children. DESIGN: Establishment of a register of school children with Down's syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre. SUBJECTS: All school age children with Down's syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8. RESULTS: 200 of 214 school children with Down's syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto's thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is >/= 8.9%. CONCLUSION: Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down's syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

Radioimmunologic determination of thyroxine in dried blood taken on blotting paper. Application ot neonaltal detection of hypothyroidism]

A blotting paper technique may be used for mass screening of neonates for hypothyroidism. The discovery of hypothyroidism in a newborn who did not have any of the classical clinical or radiological features of the condition, is reported in support of the value of the proposed method.     

Congenital or neonatal hypothyroidism with filter-paper levels of TSH less than 50 microU/ml. Conclusions on the detection strategy in France

Between 1979 and 1983, 959 hypothyroid infants were discovered by the neonatal screening program in France. Sixteen had filter-paper TSH levels between 30 and 50 microU/ml: one was athyroid, ectopic thyroid in 5,10 had thyroids in place. These latter 16 cases argue for a second TSH control-value for filter paper TSH values between 30 and 50 microU/ml.     

Amiodarone and fetal supraventricular tachycardia. Apropos of a case with neonatal hypothyroidism]

BACKGROUND. Fetal tachycardia can be a cause of in utero death. Its detection is not always easy and its treatment is still controversial. CASE REPORT. Paroxysms of supraventricular tachycardia were detected on echocardiography at the 25th week of a second pregnancy. The mother was given sotalol, but the supraventricular tachycardia became permanent. At the 27th week of gestation, sotalol was stopped and the mother was given digoxin and the foetus received 2 injections of digoxin, 10 micrograms/kg, via the umbilical cord. As this treatment was only partially effective, the mother was also given amiodarone 800 mg/day at week 28, then the dose was reduced to 400 mg/day. However, at the 31st week, the mother showed signs of digoxin intolerance, and it was replaced by sotalol. Fetal blood tests at week 34 showed a high placental transfer of digoxin and sotalol and a low fetal level of amiodarone. The newborn, a girl, was born at the 36th week having a sinus rhythm. She developed signs of hypothyroidism (T4: 4 micrograms/ml; TSH:325 microliters U/ml at 5 days of life). CONCLUSION. The placental transfers of sotalol, digoxin and amiodarone are in the range of values known to be effective. The amiodarone responsible for hypothyroidism was given to the mother because she was intolerant to digoxin. Its use must be limited to arrhythmias that are resistant to other drugs or complicated by hydrops fetalis. When used, amiodarone should not be given for more than 6 weeks, and at the lowest possible dose.     

Albright's type II osteodystrophy and hypothyroidism due to TSH deficiency. Apropos of a case in a child]

The report is dealing with a 10 year-old girl. The diagnosis of Albright's type II osteodystrophy relied on clinical, radiological and biological symptoms: evocative dysmorphic syndrome and absence of disturbances in the phosphocalcic metabolism. Hypothyroidism was secondary to an isolated defect in TSH, and a TRH stimulation test did not induce an increase in plasma TSH.     

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.     

Low TSH congenital hypothyroidism: identification of a novel mutation of the TSH beta-subunit gene in one sporadic case (C85R) and of mutation Q49stop in two siblings with congenital hypothyroidism

Isolated congenital hypothyroidism resulting from mutation of the TSH beta-subunit gene, has rarely been reported. In the present article, we report a new mutation (C85R) in exon 3 of the TSH beta-subunit gene in one sporadic case and the mutation Q49stop in two siblings with congenital hypothyroidism. The novel mutation is a T to C transition at codon 85, resulting in a change of cysteine to arginine (C85R) of the ss-subunit. Because the cysteine residues of all glycoproteins are highly conserved, this mutation is expected to result in conformational changes of the ss-subunit, rendering it incapable to form a functional heterodimer with the alpha-subunit. The second mutation described is a C to T transition resulting in a premature stop at codon 49 (Q49stop), leading to the formation of a truncated protein. Although the two siblings reported herein carried the same mutation, they had slightly modified clinical and biochemical phenotype. The mutation C85R and the previously described E11stop have, thus far, exclusively been detected in Greek patients. The Q49stop mutation initially detected in Greek patients was subsequently identified in an Egyptian girl and most recently in two Turkish siblings. These three reports possibly indicate the presence of a mutational hot spot on the TSH beta-subunit gene. Hence, with the novel mutation herein reported, a total of five mutations of the TSH beta-subunit gene are recognized as a cause of low-TSH congenital hypothyroidism worldwide.     

Comparison of T4, T3, rT3 and TSH concentrations in cord blood and serum of infants up to 3 months of age

T4, T3, TSH and rT3 concentrations were measured by radioimmunoassay in cord and postnatal (8--94 days of age) serum samples from randomly selected normal newborn infants (Group I). T4 and TSH levels also were determined in cord and postnatal sera from an additional group of apparently healthy infants 8--260 days of age, whose cord serum T4 levels were in the upper or lower 10% of the normal range of values (Group II). Postnatal T4, T3 and TSH concentrations were stable over this age range; there were no significant differences between male and female infant samples. However, there was a significant decrease in serum rT3 concentrations from 8 to 50 days of age. For the Group I infants, there were significant positive correlations between cord serum T4 and postnatal serum T4 levels, cord serum TSH and postnatal serum TSH levels, and cord serum rT3 and postnatal serum rT3 concentrations. For Group II infants, a significant positive correlation was found for cord T4--postnatal T4 serum concentrations.     

A new strategy of neonatal screening for cystic fibrosis. The association of immunoreactive trypsin and molecular biology in dried blood

Cystic fibrosis (CF) screening by means of immunoreactive trypsin (IRT) lacks specificity: only 1 out of 12 hypertrypsinemic neonates has cystic fibrosis. We propose here to analyse the KM.19 polymorphic site in the dried blood spots as an additional test in hypertrypsinemic neonates. A blind retrospective study of 114 hypertrypsinemic samples has been performed after polymerase chain reaction. Twenty-seven of 37 CF (74%) were homozygous for allele 2 (2-2) and could have been diagnosed on the 15th day of life. Fifty-five percent of the infants tested were homozygous for allele 1 (1-1), a very rare feature in CF, conferring them a probability of being normal of 99.8%. At the moment, this test could be of great help in the CF screening, even better than the search for the delta F508 mutation for which 45.9% of CF patients are homozygous.     

Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1

OBJECTIVE: To study the NKX2-1 gene in two half-siblings with elevated thyroid-stimulating hormone (TSH) on state screen, prolonged neonatal respiratory distress despite term gestations, and persistent ataxia, dysarthria, and developmental delay. STUDY DESIGN: We amplified and sequenced DNA samples from blood or buccal swab for subjects and their unaffected siblings. RESULTS: The same mutation that prevents splicing together of exons 2 and 3 of the NKX2-1 gene was present in the affected siblings, their mother, and maternal grandmother but not in their unaffected siblings. The mutation was present in the heterozygous form, thus explaining the disease phenotype. CONCLUSIONS: Autosomal dominant transmission of mutations of NKX2-1 may cause congenital hypothyroidism, neonatal respiratory distress at term, and persistent neurologic findings such as ataxia, choreoathetosis, and dysarthria in families with affected subjects in multiple generations.     

Congenital hypothyroidism in a young man with growth hormone, thyrotropin, and prolactin deficiencies.

A growth-retarded, mentally deficient, young man is described with diminished secretory response of growth hormone, thyrotropin, and prolactin to the pharmacologic stimuli of insulin, arginine, chlorpromazine, and thyrotropin-releasing hormone. Gonadotropin and ACTH functions were normal both basically and upon pharmacologic stimulation. Additionally, the patient was unresponsive to exogenous thyrotropin injections. These data suggest that the hypothyroidism in this patient was due to combined thyroid dysgenesis and pituitary insufficiency, i.e., primary and secondary hypothyroidism.     

Early bacteriologic, immunologic, and clinical courses of young infants with cystic fibrosis identified by neonatal screening

To understand better the events associated with the initiation of lung disease in young children with cystic fibrosis (CF), we prospectively performed a longitudinal study examining the early bacteriologic, immunologic, and clinical courses of 42 children with CF diagnosed after identification by neonatal screening. Serial evaluations included history and physical examination, chest radiographs, throat cultures for bacteria, and determinations of serum immunoglobulin levels and circulating immune complexes. At a mean follow-up age of 27 months, 19% of the children had serial throat cultures positive for Pseudomonas aeruginosa; the first positive culture was found at a mean age of 21 months. In three infants the initial P. aeruginosa isolates were mucoid. As determined by typing with a DNA probe, serial P. aeruginosa isolates from each patient were identical over time but were genetically distinct from isolates recovered from other patients. Of 11 infants with P. aeruginosa, nine (82%) had previous isolates of Staphylococcus aureus or Haemophilus influenzae; all had received prior antibiotic therapy. In comparison with other infants with CF, children with P. aeruginosa grown on serial throat cultures more frequently had daily cough (p less than 0.01), lower chest radiograph scores (p less than 0.05), and elevated levels of circulating immune complexes (p less than 0.01). None of the study infants had persistent hypogammaglobulinemia or hypergammaglobulinemia. We conclude that (1) S. aureus and H. influenzae remain the isolates most frequently recovered from infants with CF; (2) initial recovery of P. aeruginosa by throat culture is often preceded by the onset of chronic respiratory signs; (3) elevations of circulating immune complexes can occur early, often after the initial recovery of P. aeruginosa; and (4) early P. aeruginosa isolates are genetically distinct, demonstrating the lack of cross-colonization in this newborn population.     

Long-term consequences of the early treatment of children with congenital hypothyroidism detected by neonatal screening in Nanjing, China: a 12-year follow-up study

This study was performed to investigate the prevalence of congenital hypothyroidism (CH) in neonates in Nanjing, China and the long-term consequences of early treatment. A total of 442?454 neonates were screened for CH and 183 neonates were confirmed, with a prevalence of 1 in 2418. Of these, 163 neonates completed the follow-up process and 163 healthy children were recruited as the control group. The height, weight and body mass index (BMI) of the children with CH from 0.5 to 6 years were not significantly different from the control group (p?>?0.05). The children with CH had a significantly increased risk for being overweight or obese between 0.5 and 6 years (p?相似文献   

Anaerobic infection in a neonate. Early detection by gas liquid chromatography and response to metronidazole.

A case of presumptive anaerobic infection in a neonate is described to illustrate the use of gas-liquid chromatography in the early detection of these potentially serious pathogens. Metronidazole is suggested as a possibly useful antimicrobial agent in these infections.     

Triiodothyronine nuclear receptors in liver, brain and lung of neonatal rats. Effect of hypothyroidism and thyroid replacement therapy

In this study we have examined the effect of neonatal hypothyroidism and triiodothyronine (T3) replacement therapy on the maximal binding capacity (MBC) and the affinity of T3 receptors prepared from liver, brain and lungs. Rats were radiothyroidectomized at birth and administered T3 or its placebo starting at 8 days of age. The thyroid state in normal, hypothyroid and hypothyroid T3-treated rats was assessed by serum determination of thyroxine, T3 and by the measurement of the hepatic alpha-glycerophosphate dehydrogenase. The animals were sacrificed at 8, 16 or 24 days of age and the T3 binding was estimated in isolated nuclei and in salt nuclear extracts. The MBC of the T3 receptors was higher in the hypothyroid rats at all ages when it was determined in isolated nuclei, but not when was measured in nuclear extracts. At 8 days, the MBC had risen twofold or more in the receptors from brain (1.0 +/- 0.37 vs. 0.4 +/- 0.1 ng T3/mg DNA in controls) and from lungs (0.6 +/- 0.25 vs. 0.3 +/- 0.15 ng T3/mg DNA in controls), but was only slightly elevated in the hepatic receptor (0.62 +/- 0.08 vs. 0.48 +/- 0.15 ng T3/mg DNA in controls). At 16-24 days, the highest value of MBC was observed in the hepatic receptor (0.83 +/- 0.04 vs. 0.41 +/- 0.1 ng T3/mg DNA in controls) followed by the brain receptor (0.65 +/- 0.03 vs. 0.35 +/- 0.02 ng T3/mg DNA in controls), and that of lung (0.39 +/- 0.07 vs. 0.20 +/- 0.03 ng T3/mg DNA in controls).(ABSTRACT TRUNCATED AT 250 WORDS)