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Naphtali Brand, Ruwen A. Kathein, and Gideon Hasis

ABSTRACT

A parallelism in the incidence of human and bovine goitre in the northern part of Israel is described.

Among 1475 children and adolescents from 8–18 years of age of both sexes and examined from Upper Galilee an average incidence of goitre of more than 10% was found.

A three years follow up study showed an increase in percentage of goitre to 30% among girls. No cretins or deaf or dumb subjects were found.

Thyroid weights of 385 heads of cattle slaughtered at the slaughter-houses or on the farms were determined. While the mean weight of thyroids of cattle from a non-endemic control area was 17.7 g the mean weight for the goitrous area attained 23.4 g. The mean relative thyroid weights for the control and goitrous areas were 3.75 and 6.98 g/100 kg respectively. The histopathological examination of several excised non selected thyroids from Upper Galilee showed pathological findings: hyperplasia, fibrosis, nodular goitre.

These data are the first evidence of the incidence of endemic goitre of cattle in Israel and suggest most strongly that here the unfavourable environment plays a decisive role among the factors which influence the weight of bovine thyroids.

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Paul van Trotsenburg, Thomas Vulsma, André M. Bloot, Reindert D. Van der Gaag, Jan Willem Lens, Hemmo A. Drexhage, and JanJ. de Vijlder

Abstract.

Antibodies against the so called 'second colloid antigen' (CA2 antibodies) occurred in 51% of the mothers of hypothyroid children detected by screening for neonatal congenital hypothyroidism in Quebec (N = 49) and in The Netherlands (N = 26). In The Netherlands where corresponding neonatal serum was available, 31% (8 of 26) of the infants with congenital hypothyroidism were positive for antibodies against the second colloid antigen. When during follow-up, 3 to 5 years after diagnosis, the mothers and their children were investigated, 46% (7 of 15) of the mothers were positive for antibodies against the second colloid antigen, whereas 29% (4 of 14) of the hypothyroid children were also positive. Various control groups did not show more than a 12% positivity. This presence of thyroid-reactive antibodies in a proportion of the hypothyroid children 3 to 5 years after diagnosis is not compatible with a mere transplacental passage; it indicates that the antibodies must be produced by the mothers and by the children themselves. We conclude that a thyroid autoimmune response occurs in a considerable part of infants with congenital hypothyroidism and their mothers and that this immune response seems to persist in both of them for years.

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Pierre Ferrier and Thérèse Lemarchand-Beraud

Very little is known yet about thyroid hormone transport capacity of the serum and thyroid hormone protein binding in children. Except for the studies by Haddad (1) and by Dreyer and Man (2), all observations so far published are concerned with hormone transport mechanisms in the adult. In order to establish reference values, thyroid function tests were performed in 35 eumetabolic children (20 boys and 15 girls) aged from 6 weeks to 11 years. In vitro erythrocyte uptake of T3 was measured according to the procedure of Hamolsky et al. (3). Protein binding of T4 was studied at progressive degrees of saturation by paper electrophoresis in tris-maleate buffer at pH 8.6 according to Ingbar et al. (4). Values were compared with those from a group of 21 euthyroid adults, tested in the same laboratory. PBI was found to be higher in children than in adults. This tendency has been noted

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J Bellone, G Aimaretti, MR Valetto, S Bellone, C Baffoni, E Arvat, S Seminara, F Camanni, and E Ghigo

Bellone J. Aimaretti G, Valetto MR, Bellone S, Baffoni C, Arvat E, Seminara S, Camanni F, Ghigo E, Acute administration of recombinant human growth hormone inhibits the somatotrope responsiveness to growth hormone-releasing hormone in childhood. Eur J Endocrinol 1996:135: 421–4. ISSN 0804–4643

In adulthood the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) is inhibited by previous acute administration of either GH or GHRH and it is restored by substances that inhibit hypothalamic somatostatin release. Because in children the GH response to GHRH is not affected by previous neurohormone administration, it has been suggested that in childhood a GH increase is not able to trigger the somatostatin-mediated negative GH autofeedback mechanism. To verify this hypothesis, in 25 children (8 girls and 17 boys; 15 prepubertal and 10 in pubertal stages II–IV) with familial short stature (normal height velocity and insulin-like growth factor I levels) we studied the effect of acute iv administration of different recombinant human GH doses (group 1, N = 5, 0.06U/kg; group 2, N = 6, 0.01 U/kg; group 3, N = 7, 0.005 U/kg at −150 min or saline on the GH response to GHRH (1 μg/kg iv at 0 min). In another group (N = 7), we studied the effect of 0.005 U/kg iv recombinant human GH or saline on the GH response to GHRH combined with arginine (0.5 g/kg iv over 30 min), which likely inhibits hypothalamic somatostatin release. Serum GH increases after recombinant human GH were dose-dependent (GH peak, mean±sem, 171.7 ± 24.4, 33.3 ± 3.9 and 21.8 ± 5.1 μg/l, respectively). The administration of recombinant human GH strongly inhibited the GHRH-induced GH rise in all groups (group 1, 7.1 ± 1.7 vs 23.1 ± 7.6 μg/l, p < 0.05; group 2, 9.5 ±2.8 vs 26.9±8.5 μg/l, p < 0.05; group 3, 9.1 ±2.7 vs 34.8 ± 7.2 μg/l, p< 0.02). The GH response to arginine + GHRH (56.9 ± 13.3 μg/l) was higher than that to GHRH alone recorded in group 1 (p < 0.005), group 2 (p < 0.01) and group 3 (p < 0.01), while exogenous recombinant human GH failed to inhibit it (45.0 ± 9.4 μg/l). Our results demonstrate that in childhood, as well as in adulthood, recombinant human GH administration inhibits the somatotrope responsiveness to GHRH. This inhibitory effect is likely to be mediated by hypothalamic somatostatin release.

Ezio Ghigo, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy

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D. Gupta and W. A. Marshall

ABSTRACT

A longitudinal study was made of the daily urinary excretion, on or near each birthday, of a number of C19 and C21 steroids in 9 healthy girls and 5 healthy boys aged 3 to 7 years. The amount of androsterone excreted by each individual increased slowly during the period of study but the absolute amounts varied greatly between individuals. The excretion of aetiocholanolone was greater than that of androsterone, contrary to reported findings in older children. Small amounts of DHA were found. Testosterone was found in only about 40% of samples; epitestosterone in 70 % and 11β-OH-androsterone in only 62 %. Cortisol metabolites were excreted in amounts which increased with age and all three metabolites of corticosterone were present in most specimens. 11-Deoxycortisol was found in about 50 % of the samples and THS in 63 %. The mean trend in the ratio of glucuronides to sulphates of the 11-deoxy-17-oxosteroids decreased with increasing age, but the 11-deoxy-11-oxy ratio of 17-oxosteroids increased as did the 5α/5β ratio of the C19 and C21 steroids.

No sex differences were observed. The excretion of cortisol metabolites showed a positive correlation with height and weight. 11-Deoxy-17-oxosteroids were positively correlated with the weight. No significant relationships between steroid excretion and skeletal maturity were found.

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S Bellone, F Prodam, S Savastio, D Avanzo, A Pagani, L Trovato, G E Walker, G Genoni, and G Bona

Context

Ghrelin is a peptide with multiple functions that circulates in acylated (AG) and unacylated (UAG) forms. However, the role of ghrelin in neonates (NN) remains to be clarified.

Objective

The aim of this study was to determine ghrelin concentrations of the two forms in NN to clarify their biological roles. As such, ghrelin levels at birth were compared with those in later life.

Setting and design

Tertiary Care Center. In this cross-sectional study, we evaluated AG, UAG, AG/UAG ratio, and insulin levels in venous cord blood from NN and in fasted normal weight (NW) and obese (OB) children, both prepubertal and pubertal.

Subjects

We studied 82 NN, 82 NW, and 58 OB children.

Results

AG levels were lower in NN than in NW and OB children (P<0.0001), more specifically the prepubertal NW and OB children (P<0.0001). UAG levels were higher in NN than in NW and OB children (P<0.0001). Therefore, the AG/UAG ratio was lower in NN than in NW and OB children (P<0.0001). NN showed insulin levels similar to NW and lower than OB children (P<0.0001). At birth UAG was positively correlated with AG (Pearson: 0.425; P<0.0001) and negatively with insulin (−0.253; P<0.02). In NW and OB, UAG and AG were positively correlated to each other and negatively correlated with insulin and body mass index (−0.566; P<0.0001).

Conclusions

NN compared with children, showed higher UAG and lower AG levels. The AG/UAG ratio showed a very different profile in NN, being lower than in NW and OB children, thus suggesting a different metabolic function for the two forms in NN. Further studies are needed to clarify the exact role of the different ghrelin forms in NN.

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Salvador Villalpando, Ignacia Cisneros, Guadalupe García-Bulnes, Bárbara Urquieta, Lourdes Mondragón, Elisa Junco, and Adalberto Parra

Abstract.

Anti-thyroid antibodies are frequently found in otherwise normal populations (4.5–25.8%); however, there is scanty information about thyroid function status in affected individuals. In this report, the serum concentrations of TSH, T3, T4, rT3 and TBG and the titre of anti-thyroglobulin and anti-microsomal antibodies (haemagglutination technique) were studied in 520 healthy school children (260 boys and 260 girls) aged 6.0–17.9 years. Titres equal or greater than 1:16 of one or both antibodies were detected in 58 boys and in 77 girls (in 33 boys and in 24 girls with, and in 25 boys and 43 girls without, associated abnormalities in the serum concentrations of one or several hormones). The age distribution of thyroid antibodies followed a trimodal pattern with peaks at 7, 11 and 16–17 years in both sexes. The most striking finding was an abnormally elevated T3 concentration in 22 boys and 5 girls with positive antibodies, with no symptoms of thyroid dysfunction and with no clear relationship with simultaneous abnormalities in TSH, T4 or rT3; however, in 5 boys the TBG serum levels were increased. Serum from these patients was incubated with [125I]T3 before free radioactivity was precipitated with dextran-coated charcoal and the aliquots were analyzed by paper electrophoresis. Serum samples with high T3 levels bound significantly more radioactivity than normal or T3-free serum (P < 0.001) and an abnormal peak of radioactivity was present in the gamma globulin fraction, in the former but not in the latter two types of sera. The presence of high serum T3 levels in the absence of clinical symptoms of hyperthyroidism was probably due to sequestration of T3 by the anti-thyroglobulin antibody, which may have cross-reactivity with T3 and T4, as has previously been demonstrated both in animals and humans.

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J. Sólyom, G. Gács, K. Keszei, K. Láng, J. Örley, I. Petheö, and L. Ságodi

Abstract. We investigated the value of serum levels of adrenal steroids (dehydroepiandrosterone sulphate, testosterone, 17-hydroxyprogesterone, cortisol) in the identification in peripubertal females with late-onset congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Among 68 females (age 3–18 years) with virilization in childhood, peripubertally or postpubertally, we selected 21 girls for an ACTH test by measurement of basal blood-spot or serum 17-hydroxyprogesterone (17-OHP) levels. Eight of 21 patients had supranormal post-ACTH serum 17-OHP concentration (57–153 nmol/l) with low normal cortisol concentration. All of them had supranormal basal and post-ACTH 17-OHP to cortisol ratios. These data show a relatively high incidence (about 12%) of mild 21-hydroxylase deficiency among prepubertal and adolescent girls with virilization. It is concluded that the first step in the investigation of peripubertally virilized girls should be the determination of serum 17-OHP and cortisol. Patients with basal morning 17-OHP concentration and 17-OHP to cortisol ratio above reference range should be given an ACTH test.

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Gerhard Hintze, Dieter Emrich, Klaus Richter, Hanne Thal, Horst Thal, Thomas Wasielewski, and Johannes Köbberling

Abstract. The availability of iodinated salt containing 20 mg of iodine as iodate/kg salt consumed on a voluntary basis enabled us to investigate its effect on goitre prevalence and iodine excretion in urine in a longitudinal, prospective, randomized study over 4 years. With this salt, under the assumption of a consumption of 5 g salt per day and person, an additional intake of 100 μg of iodine can be achieved. The study was performed on initially 334 children (168 boys, 166 girls) at the age of 10 years living in an area of iodine deficiency. After 4 years, 286 children still participated in the study. Initially, goitre prevalence as assessed by palpation was found to be 30.5% (37.4% in girls and 23.8% in boys). Neck circumference was found to be significantly higher in children with goitre compared with those without (30.2 ± 1.4 vs 29.4 ± 1.4 cm; P < 0.001). Iodine excretion in the urine was significantly lower in children with goitre compared with those without (40.4 ± 16.7 μg/g creatinine vs 46.1 ± 24.9 μg/g creatinine; x ± sd; P < 0.05). The children were randomly assigned to two different groups: group A (N = 146) was asked to use iodinated salt, group B (N = 188) non-iodinated salt. Over the 4 years, a continuous increase in iodine excretion in urine could be demonstrated in group A. After 1 year, it was significantly higher than in the control group that used non-iodinated salt. After 4 years, the mean iodine excretion in children using iodinated salt was 60.1 ± 24.1 μg/g creatinine in contrast to 45.1 ± 18.6 μg/g in the control group (x ± sd; P< 0.0001). However, no decrease in goitre prevalence could be documented: after 4 years, 23.8% of the children belonging to the group using iodinated salt and 22.5% of those in the group taking non-iodinated salt had a goitre. From these observations we conclude: 1. The voluntary use of a commercially available iodinated salt containing 20 mg iodate/kg leads to a significant increase in iodine intake, measured by urinary iodine excretion. Even after 4 years, the value is far below the daily iodine intake recommended by the WHO. No decrease in goitre frequency could be assessed. 2. An increase in iodine ingestion can be achieved either by increasing the iodine content of the salt or by application of iodine by alternative measures. The safest way would be to use iodinated salt exclusively, i.e. also in the food industry and restaurants. An increase in the iodine content of the salt and its continuous voluntary use would lead to a large variation in iodine intake. A higher risk of adverse reaction, e.g. iodine-induced thyrotoxicosis, cannot be excluded in susceptible persons.

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Y. Rakover, O. Sadeh, E. Sobel, A. Shneyour, and Z. Kraiem

Abstract.

Transient neonatal hypothyroidism has been observed in three successive offspring of a mother with autoimmune thyroiditis. Thyroxine replacement therapy was initiated in a 23-year-old woman with overt clinical and laboratory findings of non-goitrous primary hypothyroidism. While on such treatment, she gave birth to three infants manifesting hypothyroidism immediately after birth. The neonates were treated with thyroxine replacement therapy which was discontinued in the three siblings at ages 2½ years, 3½ years, and 13 months. Continuous observation following cessation of therapy revealed clinical and biochemical euthyroidism in the children. Thyroid scanning during the neonatal period in the first child failed to identify functional thyroid tissue, suggesting thyroid agenesis, whereas thyroid scan performed on subsequent follow-up revealed a normal gland. Sequential serum measurements of autoantibodies directed towards the thyrotropin receptor were made in the mother and third child by a cAMP bioassay. High titres (five-six fold above normal) of blocking antibodies (tested by measuring the inhibition of TSH-stimulated cAMP production of cultured human thyroid cells by serum immunoglobulin preparations) were present in the mother and newborn 10 days after birth. The levels remained persistently high in the mother, whereas they declined and were undetectable in the child at four months. Thyroid-stimulating immunoglobulin was absent in both mother and child. The data are compatible with transient neonatal hypothyroidism caused by transplacental transfer of antibodies which block thyroid response to TSH. The half-life of the maternally-derived blocking antibody in the infant was estimated as 1-2 months. This is the first report on sequential serum measurements and estimate of half-life of the blocking antibodies performed by a cAMP bioassay (using thyroid cells of human origin). Unlike the radioreceptor assay employed so far in such cases, this assay can distinguish between stimulating and blocking TSH receptor antibodies.