[Pendred syndrome among patients with hypothyroidism: genetic diagnosis, phenotypic variability and occurrence of phenocopies]. / Pendreduv syndrom u pacientu s hypotyreózou: genetická diagnostika, fenotypová variabilita a výskyt fenokopií.

BACKGROUND: Pendred syndrome (OMIM274600) is one of the causes of congenital hypothyroidism due to thyroid dyshormonogenesis. It is an autosomal recessive disease classically characterized by dyshormonogenetic goitre and sensorineural deafness. It is caused by mutations in PDS/SLC26A4 gene encoding for pendrin--an anion transporter, mostly expressed in the thyroid gland and the inner ear. The thyroid impairment in Pendred syndrome develops only in 80% of affected individuals in form of a euthyroid or hypothyroid goitre, which is rarely present at birth, when it can be diagnosed by the neonatal screening for congenital hypothyroidism. The study was aimed to identify patients with Pendred syndrome among children with congenital or postnatal non-autoimmune hypothyroidism and subsequently confirm the diagnosis by finding mutations in the PDS/SLC26A4 gene. METHODS AND RESULTS: We examined two-hundred thirty-six Caucasians with hypothyroidism diagnosed by screening or developing later in childhood. The clinical diagnosis of Pendred syndrome was based on the laboratory and ultrasonographic signs of thyroid dyshormonogenesis (elevated TSH, low T4/fT4, goitre or normal thyroid volume) in association with sensorineural hearing loss. In subjects clinically diagnosed as Pendred syndrome, we sequenced all 21 exons of the PDS/SLC26A4 gene and their flanking intron-exon junctions. Among 236 children, nine fulfilled the diagnostic criteria of Pendred syndrome. In four, the diagnosis was confirmed by identification of mutations in the PDS/SLC26A4 gene, the remaining five patients were concluded phenocopies. CONCLUSIONS: Our study confirms the high phenotypic variability of thyroid impairment in Pendred syndrome and underlines the necessity of a molecular-genetic investigation for establishing the diagnosis in regard of the great number of phenocopies. However, from the endocrinologist's point of view, the genetic testing is only reasonable in patients with congenital hypothyroidism due to dyshormonogenesis in association with sever to profound sensorineural hearing loss.

[Follow-up study of iodine status in neonates and their mothers in 2 regions of the Czech Republic after a 3-year intervention]. / Kontrolní studie jódového zásobení novorozencu a jejich matek ze dvou oblastí CR po trech letech nápravných opatrení.

BACKGROUND: The worldwide elimination of iodine deficiency is at present one of the priorities of WHO. The highest risk group with regard to sequelae of inadequate iodine supplies are even in case of a milder iodine deficiency, human foetuses during the foetal and early infantile period (endemic cognitive disorder). An epidemiological survey in three areas of the Czech Republic (Prague, Príbram, Ustí n. Labem) in 1993-95 in 5-day old infants and their mothers provided evidence of a medium grade iodine deficiency in Prague and the Príbram area. The objective of the epidemiological check-up survey of ioduria of neonates in 1997 (Prague, Príbram) is the evaluation of the success of preventive provisions which were implemented for a period and educational activities, recommendations to take 100 micrograms iodine to all pregnant and lactating mothers, fortification of infant foods with iodine, increasing and improving the standard of iodine in table salt (27 +/- 7 mg 1/kg salt as potassium iodate). METHODS AND RESULTS: In 1997 the ioduria of two groups of full-term neonates and their mothers was assessed on the fifth day after delivery. Fifty neonates and their mothers were from Prague, 50 from Príbram. Ioduria was assessed in morning urine samples by the method of Ing. Bílek (National list of laboratory items MZ, SLP type N-SPA-BANO, code Joduria (photometry), key BIAAA, published in 1997). The results were statistically computed using Bartlett's chi-aquare and Kruskalov-Vallis' H test and Student's t-test. The median of ioduria in Prague neonates was 7.93 micrograms 1/100 ml and in Príbram neonates 7.83 micrograms 1/100 ml urine. The median values of maternal ioduria were 5.90 micrograms 1/100 ml in Prague and 7.23 micrograms 1/100 ml urine in Príbram. CONCLUSIONS: The median ioduria values of neonates from two areas (Prague and Príbram), previously (93-94) in the zone of medium iodine deficiency, increased significantly during three years of intervention and in 1997 they reached normal levels of ioduria for the given age group.

[The effect of insufficient iodine intake on the size and function of the thyroid gland]. / Vliv nedostatecného prívodu jódu na velikost a funkci stítné zlázy.

BACKGROUND: The supply of iodine indisputably affects the function of the thyroid gland. It is not clear, however, as to what extent a moderate iodopenia affects common thyroid parameters. OBJECTIVES, STARTING POINT AND MAIN PURPOSE: The aim of the study is to evaluate the influence of iodopenia (ioduria below 50 micrograms of iodine per litre of urine) on the values of T4, T3, TSH, the ankle-jerk time and sonographically ascertained thyroid gland volume in randomly selected sample of Czech population from 4 regions. METHODS: Ioduria was assessed by means of Sandel-Kolthoff method, total thyroxine, triiodothyronine and thyreotropic hormone by immunoluminiscence method; the volume of the thyroid gland sonographically according to Gutekunst and the ankle-jerk reflex by electromagnetic record method. RESULTS: Iodopenia affects a majority of investigated parameters in dependence on age. T4 is significantly higher in iodopenic adults, T3 is significantly higher in iodopenic children, TSH is significantly higher in iodopenic adults and the ankle-jerk time is prolonged in iodopenic adults. The statistical significance of the effect of iodopenia on the volume of thyroid gland was not proved. CONCLUSION: Iodopenia of a mediate degree affects commonly used parameters of the thyroid gland function in dependence on age and other factors which are to be more precisely analyzed using a larger sample. The statistical significance of the effect of iodopenia on the volume of thyroid gland was not proved. (Tab. 1, Fig. 5, Ref. 13.).

[Growth in children with impairment of thyroid gland function]. / Rust u detí s poruchou cinnosti stítné zlázy.

BACKGROUND: Changes of thyroid function affect beyond doubt the growth rate and bone maturation. In particular thyroid hypofunction during the first months of life leads not only to irreversible disorders of the development of the CNS but causes also a significant impairment of growth. In older children and adolescents with a more long-lasting thyroid dysfunction milder growth disorders without mental retardation were observed. The effect on growth by thyroid hormones takes place at the level of metabolic processes of every single cell and in particular at the level of growth cartilage. The purpose of our investigation was to test the relationship between the production of the growth factor somatomedin C (insulin growth factor-1) and the thyroxine level in children with congenital hypothyroidism revealed during neonatal screening. METHODS AND RESULTS: The somatomedin (SMA) activity was examined in 13 neonates aged 10-23 days with confirmed CH. Total thyroxine (T4) and thyroid stimulating hormone (TSH) were estimated using commercial RIA kits. SMA was assessed by Hall's biological method in Schimpff and Donnadie's modification. The control group comprised 10 healthy children aged 8-20 days and 10 children aged 29-94 days. SMA was examined before and then one month after the onset of L-thyroxine treatment. Before treatment the author found in 10-23 old infants with congenital hypothyroidism significantly lower SMA values than in controls (p < 0.01 at the 1% level of significance). During treatment the SMA values in both groups were equal. CONCLUSIONS: Early hormonal substitution therapy, i.e. as soon as possible after delivery, is essential in children with congenital hypothyroidism not only for normal growth of the CNS but also for normal continuous growth.

[Comparison of basic somatometric characteristics in randomly selected populations from Prague and Vsetín]. / Porovnání základních somatometrických charakteristik u náhodne vybraných osob prazské a vsetínské oblasti.

In 1991-1992 in the Czech Republic an epidemiological survey was conducted focused on prevention of iodine deficiency and the incidence of some thyropathies. The authors examined samples of the Prague and Vsetín population selected at random. The clinical examination comprised also somatometric assessment. In a group of 1,100 subjects from Prague and Vsetín anthropometry of basic somatometric characteristics was performed (height, body weight, BMI and four skinfolds). From comparison of the two groups ensues that the Vsetín population is shorter, as compared with the Prague population, the BMI values are significantly higher and so is the percentage of subcutaneous body fat.

[D-Trp-6 gonadotropin analog releasing hormone (Decapeptyl-Depot)-- the drug of choice in central idiopathic precocious puberty]. / D-Trp-6 gonadotropin analog releasing hormon (Decapeptyl-Depot)--lék volby u centrální idiopatické predcasné puberty.

The authors submit their experience with the treatment of idiopathic precocious central puberty in two girls with the GnRH analog (Decapeptyl-Depot, Ferring Co.). The drug was administered for one an a half and two years resp., 80 mg/kg once per month. Apart from the effect on gonadarche and thelarche the pubertal growth rate was reduced to a prepubertal level and the originally accelerated bone maturation was reduced.

[Iodine deficiency]. / Jódový deficit.

The pathophysiology of endemic thyreopathies in extensive endemies is well known. In recent years considerable attention has been attracted even by moderate iodine deficiency, the result of which is not only goiter but a number of health, social and economic problems. The aim of WHO in this field is to eliminate iodine deficiency in Europe by the year 2000. The contemporary situation of the child population in the Czech Republic as far as the iodine supply is concerned, requires immediate measures.

Partial deficiency of thyroxine-binding globulin: an HLA study.

Partial thyroxine-binding globulin (TBG) deficiency, with a median TBG of 2.3 mg/l, was found in 25 mature babies with hypothyroxinaemia (3 girls and 22 boys) from our screening programme for congenital hypothyroidism during 1988-1990. Analysis of the HLA system revealed the possibility that antigen DR6 may be considered as a risk factor for TBG deficiency (44.0 vs. 19.2%) and DR2 as a protective factor (16.0 vs. 37.5%). Similar laboratory findings were also present in 16 mothers and 1 father.

[Iodine status and incidence of thyropathies in the Czech population]. / Stav zásobení jodem a výskyt tyreopatií v nasí populaci.

Based on clinical experience on the rising incidence of some thyropathies in our population, the authors examined a random sample of the Prague population. They assessed and evaluated iodinuria, the sonographic finding of the thyroid gland, the palpation finding of the thyroid and a clinical examination which comprised a detailed case-history (a questionnaire checked during the examination) and a clinical and anthropometric examination. The results indicate that iodinuria (which reflects the iodine intake) reaches the recommended optimum (above 150 micrograms iodine/l) only in 11.4% of boys, 14% men, 6.3% girls and 5.4% women. A quite inadequate intake (less than 50 g iodine/l) was recorded in 13.2% boys, 15.2% men, 17% girls and 33.1% women. When evaluating the thyroid volume, an enlarged volume is found in 20.4-58.3% and on evaluation by palpation pathological changes are found in a considerable proportion of the examined population. The findings suggest that the iodine supply of the Prague population is inadequate and the incidence of abnormal findings on the thyroid gland is high. It will be necessary to verify these findings in other random population samples from other localities. If the adverse position will be confirmed, this will call for an urgent solution, i.e. a better iodine supply of the population.

[Blood somatomedin levels in neonates with congenital hypothyroidism and phenylketonuria]. / Hladiny sérového somatomedinu u novorozencu s kongenitální hypotyreózou a fenylketonurií.

A biological method was employed for assessing the somatomedin activity (SM)-IGF I-somatomedin C: 1) in 13 10 to 23-day old children with congenital hypothyroidism (CH) before starting substitution therapy with L-thyroxine and after one month lasting therapy. SM levels were significantly lower prior to the onset of therapy than in a control group (for p less than 0.01 on 1% level). The SM levels in treated children did not differ from controls. 2) 16 children with classic phenylketonuria (PKU) were also examined of the age of 12-23 days before starting dietary treatment with restricted phenylalanine (Phe). When compared with a control group SM levels were significantly lower in the PKU group (p = 0.01 on 5% level). When stable serum Phe concentrations had been obtained, following restricted Phe intake, SM levels no longer differed from the control. However statistical correlation of Phe and SM levels was not attained.

[A nosocomial epidemic caused by adenovirus type 3 at a clinic for children and adolescents]. / Nozokomální epidemie vyvolaná adenovirem typu 3 na klinice detí a dorostu.

The authors describe an epidemic of acute viral respiratory diseases with a nosocomial character at a clinic for children and adolescents, caused by adenovirus type 3. Of 80 exposed children 26 fell ill (attack rate 32.5%). The disease took a clinical course typical for adenovirus type 3. The authors discuss the problem of respiratory infections with a viral aetiology at paediatric departments and their possible prevention.

Screening of congenital hypothyroidism in newborns in Bohemia and Moravia.

Regular examinations of thyroid function in newborn infants were started in the district of Praha 10 in 1975. Later the incidence of congenital hypothyroidism in Czechoslovakia was assessed in a pilot study including several centers in 1981. As a screening method we used the estimation of total thyroxine (T4) in a dried spot of blood obtained from a heel prick on the fifth day after birth. A total of 45,535 newborns was screened by such method and the incidence was 1:5059 of live born infants. Since 1985 the screening of congenital hypothyroidism has been extended to cover the whole territory of Czechoslovakia. Three screening centers (in Praha, Brno and Banská Bystrica) are responsible for carrying out this screening program. The first screening method employed was the determination of total thyroxine in a dried spot of blood on filter paper as mentioned above. By the end of December 1987, 313,618 samples from newborns have been assayed in Bohemia and Moravia. The incidence of congenital hypothyroidism was found to be 1:5700 of live newborn infants. The treatment of detected cases was started before the end of the first month after birth which ensured normal development of children thus afflicted. When T4 was the first method employed, a relatively high incidence of altered TBG (thyroxine binding globulin) production (1:6400) was encountered, especially in boys.

[Acute respiratory disease caused by coronaviruses]. / Akutní respiracní onemocnení vyvolaná koronaviry.

Serological evidence of coronavirus aetiology was found in 11 patients out of 218 persons examined (5%) in the period of 1986-1987, and in 23 cases out of 311 patients (7.4%) in the period of 1987-1988. Antibody titres with a minimum of four-time elevated values in paired sera using the ELISA method were considered conclusive. Coronaviruses 229E and OC43 were employed. During the first period, more persons were infected by coronavirus 229E, while in the second period, by coronavirus OC43. The disease was equally spread over all the months of the years. For example, in the 1987-1988 period, most infections occurred in February, when out of 60 examined patients, 9 were coronavirus positive (15%).

Effect of human growth hormone and somatomedin on the recovery of sheep red blood cell receptor in peripheral T-lymphocytes.

The effect of growth hormone (GH) and somatomedin (SM) on the recovery of sheep red blood cell (SRBC) receptor in trypsinized human T-lymphocytes was studied either with the use of sera from patients with acromegaly or pituitary dwarfism or after the addition of exogenous GH, SM or thymosin to human sera. It was found that GH does not show any effect on the recovery of SRBC receptor, but it may act through the increase of SM level. It was concluded that the regulation of cellular immunity may be influenced by GH through its stimulatory action on the synthesis and release of somatomedins.