PubMed Health⌕ Search

Biomedical subjects

A Ilicki

Publications and source records attributed to A Ilicki.

14 recordsLinked to original sources
PubMed1998

Linkage analysis excludes familial congenital hypothyroidism from chromosome 21.

Congenital hypothyroidism (CH) is a heterogeneous disorder with largely unknown causes, affecting 1/3000-1/4000 new-borns. Individuals with Down syndrome have a much higher incidence of CH than the normal population, probably due to the extra copy of chromosome 21. Moreover, a girl has recently been described with CH and an interstitial deletion of proximal 21q, possibly revealing a recessive disease allele on the undeleted chromosome. To establish whether chromosome 21 is also involved in the etiology of familial cases of presumably autosomal recessive CH, we investigated 22 families with recessive CH, using 10 microsatellite markers from 21q. Linkage analysis allowing for heterogeneity revealed no signs of linkage even in a small proportion of the families, and two-point analysis of the markers made it possible to exclude the long arm of chromosome 21 from containing any major disease-causing gene.

Adult↗
PubMed1997

Genetic and linkage analysis of familial congenital hypothyroidism: exclusion of linkage to the TSH receptor gene.

Congenital hypothyroidism affects 1/3000-4000 newborns. The causes of this group of disorders are still largely unknown. Although most cases are sporadic some families have several affected children and/or consanguineous parents, suggesting autosomal recessive inheritance. Furthermore, there is a murine strain (hyt) with congenital hypothyroidism and autosomal recessive inheritance, whose phenotype appears to be identical with the corresponding human disease. In the hyt mouse, the disease is caused by a mutation in the thyroid-stimulating hormone receptor (TSHR) gene, making this gene a likely candidate also for the human disease. The human TSHR gene was mapped on radiation hybrid panels and closely linked flanking markers D14S287 and D14S616 were identified. On the Genebridge 4 panel, D14S287 was found to be located 8.5 cR (corresponding to 2.3 cM) proximal to the TSHR gene, and D14S616 was found to be located 4.4 cR (1.2 cM) distal to the TSHR gene. These markers were analyzed in 23 families, most of them with two or more children affected by congenital hypothyroidism and some with appreciable consanguinity of the parents. Assuming homogeneity, the two-point lod score at theta = 0.1 was -4.8 for D14S287 and -5.8 for D14S616, and thus linkage to the TSHR gene was excluded. Even when the data were analyzed with allowance for heterogeneity, there was no evidence of linkage. Our conclusion is that if mutation of the TSHR gene causes familial congenital hypothyroidism in humans, it affects only a small proportion of the cases.

Adult↗
PubMed1997

Linear growth in early treated children with congenital hypothyroidism.

Length/height was studied from birth to 6 years of age in 103 children with congenital hypothyroidism identified by the Norwegian or Swedish screening programs. We used the "infancy-childhood-puberty (ICP) growth model". This model describes normal linear growth during the first 3 years of life by an infancy component with the addition of a childhood component, the latter acting from the second half of the first year. In comparison with reference children, children with hypothyroidism had reduced growth from 6 to 12 months, and increased growth after 12 months of age. Mean onset of the childhood component of growth was delayed from 8.1 months (SD 1.9) to 10.4 months (SD 2.2) in girls, and from 8.9 months (SD 2.0) to 11.0 months (SD 2.1) in boys. Age at onset of the childhood component was correlated with age at start of treatment (r = 0.24), and in children with more severe hypothyroidism (pretreatment serum thyroxine < 40 nmol/l) inversely correlated with the L-thyroxine dose at start of treatment (r = -0.40). Change in height standard deviation score from 1 to 3 years of age was correlated with the serum thyroxine concentration at age 1 year (r = 0.30). The delay in the onset of the childhood component of growth and the association with age at start of treatment and initial L-thyroxine dose indicate that thyroid hormones during the first months of life are essential for normal onset of the childhood component of growth, which otherwise is assumed to be growth hormone-dependent.

Age Factors↗
PubMed1996

Gene conversion in the CYP11B2 gene encoding P450c11AS is associated with, but does not cause, the syndrome of corticosterone methyloxidase II deficiency.

Cytochrome P450c11AS (aldosterone synthase) has 11 beta-hydroxylase, 18-hydroxylase, and 18-oxidase activities and is expressed solely in the adrenal zona glomerulosa. Corticosterone methyloxidase II (CMOII) deficiency denotes a rare disorder of adrenal steroidogenesis in which only the 18-oxidase activity of P450c11AS is disrupted, while the 11 beta-hydroxylase and 18-hydroxylase activities persist. Such patients have elevated serum concentrations of corticosterone and 18-hydroxycorticosterone and very low or unmeasurable concentrations of aldosterone, often resulting in a clinical salt-losing crisis in infancy. One pair of point mutations, Arg181-->Trp and Val386-->Ala, has been previously characterized to cause this disorder in an inbred Iranian Jewish population. We have sought mutations causing CMOII deficiency in outbred populations. In three of four unrelated P450c11AS alleles from two unrelated patients with CMOII deficiency, we found a gene conversion event in which exons 3 and 4 of the CYP11B2 gene encoding P450c11AS were changed to the sequence of the nearby CYP11B1 gene, which encodes the related enzyme P450c11 beta. This conversion resulted in a mutant P450c11AS protein carrying three changes: Asp141-->Glu, Lys151-->Asn, and Ile246-->Thr. We built seven vectors expressing P450c11AS carrying each mutation singly, each of the three possible pairs of mutations, and the triple mutation as found in the proband. The activities of both the normal P450c11AS and the various mutants in transfected nonsteroidogenic COS-1 cells were very low, but their activities in steroidogenic MA-10 and JEG-3 cells were 10- to 20-fold higher. In these systems all of the mutants retained normal 18-oxidase activity, indicating that the detected gene conversion event is associated with but does not cause CMOII deficiency. None of the four CYP11B2 alleles in these two patients bore other identifiable mutations. These patients might have mutations in the promoters or other noncoding regions, or mutations in genes other than CYP11B2 may cause the syndrome of CMOII deficiency.

Base Sequence↗
PubMed1992

Hyperthyroid Graves' disease without detectable thyrotropin receptor antibodies.

TSH receptor antibodies are generally held responsible for the stimulation of the thyroid that characterizes patients with Graves' disease. Here, we describe nine patients with hyperthyroidism (triiodothyronine 4.9, 3.2-6.7 nmol/L; median, range) who were referred for radioiodine treatment and who had increased thyroid radioiodine uptake values but lacked TSH receptor antibodies determined by a radioreceptor assay. Furthermore, when serum immunoglobulins were studied in a bioassay based on a rat thyroid cell line (FRTL-5), no evidence of stimulant activity was observed. Subsequent to radioiodine therapy, TSH receptor antibodies appeared in all nine patients. The antibodies competed for TSH in the radioreceptor assay and, of the eight patient samples studied with the bioassay, six stimulated cAMP production whereas another two blocked the latter. The results show that a small proportion of patients with active hyperthyroid Graves' disease, in this study 9 out of 130 cases, do not have detectable TSH receptor stimulatory antibodies. A local production of antibodies within the thyroid can be suggested, although a more likely explanation might be that the thyroid in Graves' disease is activated also by other mechanisms than antibody-dependent ones.

Adult↗
PubMed1991

Psychological development at 7 years of age in children with congenital hypothyroidism. Timing and dosage of initial treatment.

Sixty of 68 consecutive patients detected during the first two years of the Swedish screening programme for congenital hypothyroidism were Griffiths tested at the age 6.5-7.5 years. The test quotients of the patients could not be distinguished from those of a reference population. Replacement therapy with 8.7 +/- 2.8 micrograms of L-thyroxine (mean +/- SD)/kg/d had been started at 15.0 +/- 7.1 days of life. Furthermore, normal results on Griffiths tests were also found in 13 patients with delayed normalization of serum TSH, i.e. greater than 19 mU/l at the age of six weeks, as well as in patients with retarded skeletal maturity and/or very low neonatal serum levels of thyroxine, i.e. less than 18 nmol/l and tri-iodothyronine, i.e. less than 0.92 nmol/l. Our findings indicate that a replacement dose of 6-11 micrograms L-thyroxine/kg/d is adequate and allows normal psychological development if treatment is started early.

Bone Development↗
PubMed1990

Hyperthyroidism and hypothyroidism in monozygotic twins: detection of stimulating and blocking THS receptor antibodies using the FRTL5-cell line.

We present a rare history of monozygotic twin girls who at the age of 10 yr presented with hyper- and hypothyroidism, respectively. Both girls had antibodies against thyrotropin receptors as measured by a radioreceptor assay (230 U/l and 1400 U/l; reference range less than 7 U/l). The sera were further examined in a bioassay, based on a rat thyroid cell line (FRTL5), in which release of cAMP into medium was measured. The TSH receptor antibodies of the hyperthyroid twin displayed a ratio of radioreceptor to biological activity typical of Graves' disease. In contrast, the antibodies of the hypothyroid twin acted as pure antagonists at the TSH receptor level. The occurrence of TSH receptor antibodies in these monozygotic twins suggests a similar pathogenesis of Graves' disease and that of hypothyroidism due to thyroid blocking antibodies.

Adolescent↗
PubMed1990

Neonatal skeletal maturation in congenital hypothyroidism and its prognostic value for psychomotor development at 3 years in patients treated early.

Neonatal skeletal maturation was assessed by different methods based on the bone centres in the knee and ankle region in 46 infants with true-positive (patients) and 17 infants with false-positive screening tests (controls). The patients and controls did not differ in mean age at X-ray examination and age at the start of treatment (14.5 +/- 5.7 days). One of the methods used to score the size of femoral and tibial epiphyses was just as good as the other ones tested, but has the advantage of being the easiest to use and therefore clinically most suitable. Skeletal maturity assessed by this method correlated best with serum T4 (r = 0.62, p less than 0.01). Griffiths tests were performed in 37 of the 46 patients at 28-48 months of life. The best correlation obtained between neonatal skeletal maturity and Griffiths global developmental quotient at 3 years of age was r = 0.58 (p less than 0.001). Although statistically significant, it was too weak to be of clinical value in identifying individual patients at risk. We conclude that an assessment of skeletal maturation is not useful for the prognosis of psychomotor development in individual patients with congenital hypothyroidism receiving treatment within the first 2 weeks of life.

Age Determination by Skeleton↗
PubMed1988

Psychomotor development of children with congenital hypothyroidism diagnosed by neonatal screening.

The psychomotor development in 68 children with congenital hypothyroidism diagnosed during the first two years of a nationwide neonatal screening programme in Sweden was assessed during their first three years of life. Replacement therapy with thyroxine was initiated at the age of 15 +/- 7 days (mean +/- SD). Griffiths tests were performed in 15 patients at the age of 18 months and in 51 patients at 30-47 months. Their developmental quotients did not differ from those of control children, indicating that the psychomotor development in the children with congenital hypothyroidism was normal. In earlier studies of Swedish children with congenital hypothyroidism, diagnosed clinically before the age of three and a half years, the psychomotor development was found to be impaired. In contrast, the patients diagnosed by neonatal screening and given early therapy displayed normal results in Griffiths tests. This indicates that the age at the start of treatment is an important determinant for the prognosis.

Child, Preschool↗
PubMed1984

Premature thelarche--natural history and sex hormone secretion in 68 girls.

Data obtained during long-term follow-up of 68 girls with premature thelarche were analysed. In 85% onset was before the age of 2 years, in 30.8% being present at birth. In 44.1% there was a regression after 3 2/12 +/- 2 8/12 years (SD). Basal levels of plasma FSH and response to LH-RH were significantly higher than prepubertal controls (1.93 +/- 1.56 vs. 0.8 +/- 0.1 mU/ml and peaks 12.3 +/- 5.4 vs. 7.9 +/- 1.0 mU/ml respectively; p less than 0.001). Twenty-seven of 52 patients tested had increased plasma estradiol and in 27 of 40 patients tested, urocytograms or vaginal smear showed estrogenization. Basal levels of LH and response to LH-RH were prepubertal. The girls with premature thelarche were significantly taller than normal controls of the same age (p less than 0.001). These results suggest that premature thelarche is an incomplete form of precocious sexual development probably due to derangement in the maturation of the hypothalamo-pituitary-gonadal axis which results in a higher than normal secretion of FSH, as well as a defect in the peripheral sensitivity to the sex hormones.

17-Ketosteroids↗
PubMed1979

Effect of cyproterone acetate (CA) on growth and endocrine function in precocious puberty.

16 girls with precocious puberty have been studied. Following low dosage cyproterone acetate (CA) therapy (mean daily dosage 65 mg/m2BSA) a beneficial effect on growth and skeletal maturation was observed. During high dosage therapy (150 mg/m2 per day) endocrinological studies were performed in 10 of these patients. There was no significant difference in HGH levels (insulin- and arginine-test), T3 and TSH values (TRH-test) between patients and controls, T4 concentration was significantly increased. Basal prolactin levels and prolactin response to TRH was definitely elevated. Oral glucose load and arginine infusion resulted in a significantly enhanced insulin release. There was a significant reduction in basal LH levels and an increase in FSH response to LH-RH. Basal and diurnal plasma cortisol values were markedly reduced and the cortisol release due to corticotrophin injection, lysinevasopressin (LVP) injection and insulin-hypoglycemia as well. A definite increase in basal ACTH levels was observed, during LVP- and insulin-hypoglycemia test ACTH concentrations were within or significantly above normal range. In our patients a primary adrenocortical insufficiency due to CA treatment was evident.

Arginine↗
PubMedDate not supplied

The value of neonatal serum thyroglobulin determinations in the follow-up of patients with congenital hypothyroidism.

Serum thyroglobulin was determined in 68 newborn infants with positive screening tests for congenital hypothyroidism. In 38 infants the diagnosis was confirmed (patients), but the remaining 30 were euthyroid at follow-up (controls). The mean thyroglobulin concentration at the age of 2 weeks did not differ significantly between the patients and the controls (179 vs. 125 micrograms/l). Thyroid scintigraphy was performed in 15 patients. All seven with thyroid aplasia, based on 99mTc pertechnetate scintigraphy, had measurable thyroglobulin (greater than 2 micrograms/l) and thyroid hormones in their serum. This indicates that total absence of thyroid tissue is very rare in Swedish patients with congenital hypothyroidism. Scintigraphy based on 99mTc does not permit detection of small amounts of thyroid tissue. The neonatal concentrations of thyroglobulin did not correlate with the results of Griffiths test at 3 years and are therefore not useful for prognosis of psychomotor development. We conclude that neonatal measurement of thyroglobulin is of limited value in the follow-up of patients with congenital hypothyroidism.

Bone Development↗
PubMedDate not supplied

Circulating thyroid antibodies in congenital hypothyroidism.

The role of maternal thyroid antibodies in congenital hypothyroidism is controversial. We have analysed serum thyroid antibodies in patients and their mothers. In a bioassay, antibodies interacting with thyroid cells were analysed by measuring of TSH-stimulated cAMP production in a rat thyroid cell line, FRTL5. Serum antibodies against the TSH receptor, thyroid peroxidase and thyroglobulin were determined by radioreceptor assay and enzyme-linked immunosorbent assays. The bioassay was performed with IgG preparations from 89 mothers of children with congenital hypothyroidism. Analyses for TSH receptor antibodies and thyroid peroxidase/thyroglobulin antibodies were performed on 144 and 118 sera of newborn patients respectively. No evidence of an increased prevalence of thyroid antibodies was found on comparison with controls. One infant had transient neonatal hyperthyrotropinaemia because of TSH receptor blocking antibodies transferred from the mother. Our data indicate that, apart from transplacental transfer of TSH receptor antibodies, maternal immunoglobulins have a limited role in the aetiology of congenital thyroid dysfunction.

Autoantibodies↗