Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader-Willi Syndrome: A Polish Multicentre Study.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.

Correlation of Genotype and Perinatal Period, Time of Diagnosis and Anthropometric Data before Commencement of Recombinant Human Growth Hormone Treatment in Polish Patients with Prader-Willi Syndrome.

Genotype-phenotype correlation in patients with Prader-Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age-group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

Assessment of metabolic changes within normal appearing gray and white matter in children with growth hormone deficiency: magnetic resonance spectroscopy and hormonal correlation.

OBJECTIVE: The pathogenesis of idiopathic growth hormone deficiency (GHD) in children, including possible cerebral metabolic alterations, remains unclear. The aim of the study was to evaluate metabolic changes within the normal appearing brain in children with GHD using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations and with pituitary gland size. METHODS: Seventy children with GHD (mean age 7.8 yrs) and 11 healthy controls (mean age 8.4 yrs) were enrolled in the study. The MRS examinations were performed on a 1.5T scanner. Voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, Cho/Cr and mI/Cr ratios were analyzed. The metabolite ratios, pituitary gland size and hormonal concentrations: growth hormone (GH) in two stimulation tests and GH during the night, as well as IGF-1 (insulin-like growth factor) and IGFBP3 (insulin-like growth factor-binding protein) levels were also correlated. RESULTS: There was a significant (p < 0.05) decrease of the NAA/Cr ratios in PCG and PWM in children with GHD compared to the normal subjects. Other metabolite ratios showed no significant differences. We also found significant positive correlations between NAA/Cr ratio in PWM and IGFBP3 level, as well as with GH concentration in a stimulation test with glucagon. CONCLUSIONS: The reduction of NAA/Cr ratios may suggest loss of neuronal activity within normal appearing gray and white matters in children with GHD. MRS could be a sensitive marker of cerebral metabolic disturbances associated with GHD and maybe used as an additional indicator for therapy with recombinant GH.

[The effect of one year therapy with recombinant human growth hormone (rhGH) on growth velocity, calcium-phosphorus metabolism, bone mineral density and changes in body composition in children with growth hormone deficiency (GHD)]. / Ocena szybkosci wzrastania i gospodarki wapniowo-fosforanowej, gestosci mineralnej kosci oraz zmiany skladu ciala u dzieci z somatotropinowa niedoczynnoscia przysadki w pierwszym roku leczenia rekombinowanym ludzkim hormonem wzrostu (rhGH).

INTRODUCTION: The most significant effect of growth hormone treatment is growth promotion. For adults the metabolic effect is the most important. This treatment has an influence on the forming of correct composition of body mass, on metabolism of osseous tissue and bone mineral density. AIM OF THE STUDY: Comparison between the rate of growth and estimation of calcium-phosphorus metabolism, bone mineral density and change of body composition in children with growth hormone deficiency during the first year of growth hormone treatment. MATERIAL AND METHODS: The treatment included 120 children and adolescents (85 boys and 35 girls) in age from 6 to 21.5 years old (the average age: 14.2+/-3.0) who were treated in Dept. of Endocrinology and Diabetology for Children and Adolescents during the years 2002-2006 as a result of growth hormone deficiency. Children suffering from panhypopituitarism and other diseases were excluded from the research. The following parameters were included in the analysis: age and sex, age at the start of treatment, the degree of growth hormone deficiency, concentration of calcium, magnesium and phosphates in blood serum, mineral density of bones (BMD), the concentration of osseous minerals, concentration of adipose tissue and lean body mass. All the children were treated with recombined human growth hormone (rhGH) in dose of 0.7 j/kg per week. No interruption of the treatment was noticed. RESULTS: Partial growth hormone deficiency (GHD) was diagnosed in the group of 71 children (52 boys and 19 girls), total GHD diagnosed in 49 cases (34 boys and 15 girls). Average age at the start of treatment was 11.7+/-2.9 years. During the first year of treatment the rate of growing increases from 3.9+/-1,1 cm per year before treatment to 8.72+/-2.27 cm per year (p<0.01) for the whole examined group, for girls from 3.8+/-1.2 cm per year to 8.77 cm per year (p<0.01), for boys from 3.2+/-1.3 per year to 8.58+/-2.20 cm per year (p<0.01). Average concentrations of calcium, magnesium and alkaline phosphatase (ALP) in blood serum remain in accordance with laboratory standards and were statistically not significant. In the majority of patients LBM increased significantly from 28 689+/-4423 g to 35 549.09+/-2968 g (p<0,05) and FM decreased from 21 070+/-4019,8 g (33,15+/-7,6%) to 19 075.37+/-4307,3 g (26.15+/-8.6%) (p<0.05). The alternations of the body composition in GH deficient children treated with rhGH occurred during the first year of therapy.

[Causes of menstrual disorders in adolescent girls--a retrospective study]. / Przyczyny zaburzen miesiaczkowania u nastolatek--badanie retrospektywne.

INTRODUCTION: Adolescent girls often visit the outpatient endocrinological clinic because of menstrual disorders. The problem arises whether to recognize the menstrual cycle irregularity as a physiology of the adolescence or to initiate diagnostic procedures to exclude pathology. Although irregular menses during first 3 years after menarche are usually symptoms of hypothalamus-pituitary-ovary axis immaturity, it does not exclude disorders to be subject of diagnosis and treatment. THE AIM OF THE STUDY was to evaluate causes of menstrual disorders in adolescent girls, who visited the outpatient clinic of the Department of Endocrinology and Diabetology for Children and Adolescents, Wroclaw Medical University, between 2001-2005. MATERIAL AND METHODS: The study comprised 76 patients, who visited the outpatient endocrinological clinic because of menstrual disorders. Only the girls at least 2 years after menarche or with amenorrhoea primaria were included. The following parameters were analyzed: age, age of menarche, height and body mass, BMI, evidences of androgen excess, hormone levels, gynecological and ultrasound examination. RESULTS: Average age in the examined group was 16.2 years (min 12.5, max 20), average age of menarche was 12.5 years. Evidence of androgens excess were found in 48 patients (63.2%). The girls were coming to the clinic most often because of rare menses, most rarely because of primary lack of menstruation. Depending on the type of disorders they were divided into five groups: group I--amenorrhoea primaria--4 patients (5.3%), group II--amenorrhoea secundaria--14 patients (18.4%), group III--oligomenorrhoea--38 patients (50%), group IV--polymenorhea--8 patients (10.5%), group V--mixed disorders--12 patients (15.8%). The causes of menstrual disorders depended on the group. CONCLUSIONS: 1. Menstruation cycles irregularity in the first years after menarche may be a symptom of pathology demanding diagnosis and treatment. 2. PCO should be taken into consideration as a frequent cause of menstrual disorders in adolescent girls.

[The bone mineral density and the markers of the osseous circle in children with non-toxic parenchymatous or nodular goiter long-time treated with L-thyroxine]. / Ocena gestosci mineralnej tkanki kostnej oraz markerów obrotu kostnego u dzieci dlugotrwale leczonych syntetyczna lewotyroksyna z powodu nietoksycznego wola rozlanego i guzkowego.

The aim of the study was the appreciation of the influence of a therapy with L-thyroxine on the metabolism and density of the osseous tissue (BMD) in children with an euthyroid diffuse and nodular goiter. The examinations included 50 children (5 boys and 45 girls). Mean age of the investigated group: 17 years, time of therapy 2-5 years. The daily dose of L-thyroxine was not higher than 1-2 microg/kg body mass. All the children were in clinical and hormonal euthyrosis. The control group consisted of 50 healthy children (12 boys and 38 girls), mean age 16,16 years. A correlation between the age of the children, TSH level and the markers of the osseous circle was not observed. The mean level of TSH was statistical significant lower in the examined group. In the examined group the level of PTH and ICTP in the blood serum was (PTH: 35.83+/-8.34 pg/m vs 37.21+/-7.17 pg/ml); ICTP (8.7+/-3.87 microg/l vs 15.11+/-5.7 microg/l) was lower in the control group but the difference was statistical not significant (p=0.07). The mean concentration of PICP in the investigated group was significant lower in comparison with the control group. The mean level ICTP between the examined and control group was statistical significant (p<0.05). The mean concentration of osteocalcine (OC) in the treated with L-thyroxine was statistical not significant.

Chronic autoimmune thyroid disease in children and adolescents in the years 1999-2004 in Lower Silesia, Poland.

The aim of the study was to analyze data related to chronic autoimmune thyroid disease at diagnosis and at follow-up of children and adolescents in Lower Silesia in the years 1999-2004. Age, gender, incidence of thyroid disease in the family, clinical presentation, hormonal findings, levels of thyroid antibodies, results of ultrasonography, and fine needle aspiration biopsy (FNAB) were recorded. 100 children, 10 boys and 90 girls, were included in the analysis. The mean age at diagnosis was 12.3+/-2.3 years and at last examination 14.9+/-1.9 years. At diagnosis, increased levels of TSH without overt hypothyroidism was observed in 26 children. In 11 children hyperthyroidism was detected whereas 63 children were euthyroid. An increased level of thyroid peroxidase antibodies was observed in 65% of the children. Ultrasonography was characteristic for Hashimoto's thyroiditis in all patients. Fine needle biopsy was performed when there were diagnostic difficulties (35% children). Thus, in all the children the diagnosis of Hashimoto's thyroiditis was ascertained either by high antibody titer or FNAB. Associated diseases were observed in 33% of the children. Thyroid disease in the family was present in 25% of the children. There was a gradual decline in the number of new cases presented from 1999 to 2004. The reason for this decline remains speculative.

[Personal observations of puberty in girls after unilateral ovariectomy]. / Wlasne obserwacje dotyczace przebiegu okresu dojrzewania u dziewczat po jednostronnej owariektomii.

The authors present the course of puberty in three girls after surgery because of hormonally active ovarian tumours diagnosed and operated at the age of 3, 6 and 9 years, respectively. In the youngest patient with folliculoma ovari chemotherapy was also given, and girl No. 3 with luteinic capsule was treated for one year with decapeptyl because idiopathic precocious puberty was diagnosed. At present all three girls are in good physical condition with age-adequate development and puberty.