Endokrynologia, diabetologia i choroby przemiany materii wieku rozwojowego : organ Polskiego Towarzystwa Endokrynologow Dzieciecych最新文献

Background and aim of the study: Our own studies confirm the hypothesis, that insulin resistance of various degree is often observed in children and adolescents with type 1 diabetes mellitus (T1DM). The knowledge of this parameter characterizing individual patients may be of great value not only for better understanding of the disease course but also as a potential source of specific treatment. Reliable estimation of insulin resistance with hyperinsulinemic euglycemic clamp is a complex, laborious and costly procedure. These facts were enough to motivate us to make an attempt to elaborate an indirect, simplified method of insulin resistance assessment in T1DM children, that would be based on patients characteristics and on clinical parameters of the disease course.

Materials and methods: 142 children and adolescents with T1DM (79 boys, 63 girls) aged 7.7-20.3 years (mean age - 13.7+/-3.3 years) were included into the study. Duration of diabetes was 0.5-12.5 years (mean 2.7+/-2.3 years). The stage of puberty was assessed by the Tanner scale. Euglycemic-hyperinsulinemic clamp by de Fronzo was performed to estimate insulin resistance. Glucose disposal rate (M index) determined during the last 30 min of the test estimated insulin resistance. Looking for clinical and metabolic factors characterizing insulin resistance: a) the plasma cholesterol, HDL-Ch, triglycerides and HbA1c were examined, b) the height, weight, waist circumference and blood pressure were measured, c) body mass index and daily dose of insulin were calculated. For statistical analysis the multiple regression was used (forward stepwise method).

Results: In the study group M index ranged from 2.1 to 17.4 mg/kg/min (mean 7.27+/-2.62 mg/kg/min). The boys presented better insulin sensitivity than girls (7.79 vs. 6.62, p=0.008). The insulin resistance depended on the patients' age (r=-0.46, p<0.001) and stage of puberty (p<0.001). A correlation between M index and insulin dose (r=-0.34, p<0.05) and HbA1c (r=-0.17; p=0.04) were found. There was a significant relationship between M index and parameters of adiposity, lipids and blood pressure. All significant clinical parameters of insulin resistance were subjected to the analysis. Multiple linear regression analysis was performed. The model with the strongest correlation with index M was used to work out the formula: M index = 17.065 + 1.547 x (gender: boys=1, girls=0) - 0,183 x (age) - 0,117 x (Waist circumference) - 2,019 x (Daily insulin dose) - 0,016 x (LDL-CH) + 0,041 x (DBP).

Conclusion: In T1DM children and adolescents it is possible to estimate for daily use extent of insulin resistance on the basis of clinical features.

Background: Body mass deficit at birth is one of the characteristic features observed in Turner's syndrome (TS). Body mass is lower than expected for gestational age in about 90% of TS-babies, and is below -2 SD (i.e. "small for gestational age") in about 20% of patients.

Objectives: The aim of the study was to compare the growth courses of TS-girls born with normal and deficient body mass.

Patients: A group of 157 TS-girls, delivered at term (> or =38 weeks of gestation), were studied. Body mass of 80 girls ranged from -0.5 to +0.5 SD and body length was above -2 SD (AGA group); another 54 girls had body mass below -2 SD and body length above -2 SD (disproportional SGA group), and 23 girls had both body mass and length below -2 SD (proportional SGA group).

Methods: Turner's syndrome was confirmed by chromosome analysis. Body mass at birth (BMB) was related to the norms for gestational age (GA) designed by Usher and McLean. Newborns, whose BMB was lower than -2 SD for GA, were considered small for gestational age (SGA). Postnatal body height and mass values were related to Polish norms for females with Turner's syndrome and to the norms for healthy female population.

Results: In the spontaneously growing TS-girls from the AGA group, a total of 275 measurements of body mass and height were carried out, the respective numbers for DSGA and PSGA groups were 176 and 100. Mean differences between the actual and expected body height for the AGA, DSGA and PSGA groups amounted to 0.40+/- 1.02, -0.21+/-0.88 and -0.95+/-0.80 SD TS, respectively, all means differing highly significantly (p<0.001) from each other.

Conclusion: It may be concluded that spontaneously growing girls with Turner's syndrome, who had a normal (for gestational age) body mass at birth, attain a higher stature than girls with body mass deficit.

Introduction: The cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a transmembrane molecule present on T cells that plays a critical role in the down regulation of antigen-activated immune response. Its gene polymorphism is a strong candidate gene for conferring susceptibility to thyroid autoimmunity. THE AIM of the study was to analyse the surface CTLA-4 (CD 152) expression on peripheral blood lymphocytes.

Material and methods: Blood samples from 66 children were analysed: 36 with Hashimoto's thyroiditis and 30 healthy, age-matched controls, mean age: 13.4 years. The percentages of peripheral blood lymphocyte subsets were analysed by evaluation of CD antigens surface expression with three colour flow cytometry using Coulter EPICS XL cytometer. CD28, CD152, CD4, CD8 antigens were evaluated. Statistical analysis was performed using t- test and other tests of the Statistica programme. P-value <0.05 was considered as statistically significant.

Results: In children with Hashimoto's thyroiditis the surface expression of CD8(+) CD152(+) T cells was statistically significant lower than in healthy controls. P-value was 0,02. Percentage of other CD examined in the study did not differ significantly in patients and in the control group.

Conclusion: In children with Hashimoto's thyroiditis the surface expression of CTLA-4 (CD152) on peripheral blood lymphocytes CD8(+) was statistically significantly lower than in healthy controls.

Introduction: The modern therapy of Hodgkin's disease (HD): chemotherapy (CT) or/and radiotherapy (RT) gives a chance of a long time survival but it brings a possibility of early and late complications including thyroid gland function disorders (post-radiotherapy thyroiditis, thyroid hypofunction, Graves disease, thyroid nodules, thyroid cancer).

Aim: Evaluation of thyroid gland function in patients with total HD remission status from 6 to 16 years after the treatment.

Material and methods: The study included 29 patients suffering from HD (9 women, 20 men, mean age 22.8 years), treated with CT (cycles MVPP and B-DOPA) and with RT (cervical region; 18-40 Gy) in their childhood. The patients were examined by palpation, ultrasound, fine-needle aspiration biopsy. The thyroid gland on the average 6 (1st examination) and 16 years (2nd examination) after the treatment as well as thyroid hormones (TSH, fT3, fT4), thyroglobulin (Tg) and anti-thyroid antibodies in blood serum were estimated. The results were analyzed statistically; the percentage of abnormal results of estimated hormones with reference range was calculated.

Results: There were no abnormalities in thyroid palpation examination in any patient. The mean thyroid volume in ultrasound in 2nd examination cor-responded to 66.3% of healthy individuals thyroid volume. In 8 patients thyroid nodules were found, in one thyroid papillary carcinoma was diagnosed. In one patient (3.4%) the features of subclinical thyroid hypofunction and in 17.2% the increased level of Tg in blood serum with normal thyroid hormone levels were found. In two patients (6.8%) the raised titre of a-TG and a-TPO was observed.

Conclusions: 1. In majority of patients with HD after RT in cervical region in long term remission period the normal thyroid function was observed. 2. Due to thyroid cancer hazard even many years after radiotherapy regular morphological thyroid evaluation is necessary.

Unlabelled: In males AMH is produced by the testes from fetal life to puberty. The main role of AMH in the male fetus is to cause Müllerian duct regression, in prepubertal boys AMH is involved in testicular development and function. THE AIM OF THIS STUDY was to assess the use of a sensitive assay kit of AMH measurements in the diagnosis and management of children with abnormal sexual differentiation and cryptorchidism. We also compared the serum AMH levels with testosterone levels after hCG stimulation.

Methods: We assessed serum AMH levels in 79 prepubertal patients: gonadal dysgenesis (n=23), partial androgen insensitivity (n=4), scrotal hypospadiasis (n=16), bilateral cryptorchidism (n=20), anorchia (n=10) and unilateral cryptorchidism (n=6). Earlier hCG test was performed (one dose of 2000 IU/m2 i.m.) and testosterone levels were determined.

Results: AMH level was not impaired in patients with unilateral cryptorchidism and partial androgen insensitivity (median 350 pmol/l). AMH was normal in most of boys with scrotal hypospadiasis (median 317 pmol/l). Significant differences were observed between AMH levels in boys with hypospadias and patients with gonadal dysgenesis (median 174 pmol/l; p<0,001). In the cryptorchid group AMH level was normal in 50% of boys. There was a significant difference between AMH levels in cryptorchid boys (median 249.5 pmol/l) and patients with anorchia; (p<0,001). AMH levels were almost undetectable in boys with vanishing testes (median 1.0 pmol/l). The basal AMH levels were correlated with testosterone response to hCG.

Conclusions: When testes are non-palpable a single measurement of serum AMH level can distinguish between cryptorchidism and anorchia. AMH determination can help in the diagnosis of intersex conditions. Our data demonstrated that basal AMH measurements correlate with testosterone response to hCG. Serum AMH concentration in prepubertal children is a marker of testicular function. Preoperative measurement of AMH can be useful in the management of children with cryptorchidism and intersex disorders.

Introduction: Abnormal activation of the matrix metalloproteinases (MMPs) in diabetes mellitus leads to extracellular matrix changes through the structural protein composition changes. The metalloproteinases inhibitors (TIMPs) are regulatory factors in this activity. Not all regulating mechanisms are completely known, especially in patients with type 1 diabetes.

The aim of study: evaluation of MMP-2, MMP-9 and TIMP-1, TIMP-2 levels in children and adolescents with type 1 diabetes.

Material and methods: 74 patients in the mean age 15 years (+/-3.0) suffering from type 1 diabetes for mean 6.6 years (+/-3.6) took part in the study. Patients were treated with flexible multiple daily insulin (n=54) and with continuous subcutaneous insulin infusion - personal insulin pump (n=20). MMP-2, MMP-9, TIMP-1 and TIMP-2 blood serum levels were measured in all patients. 45 healthy persons matched for age, without atherosclerosis risk factors, with proper BMI and lipids levels were in the control group.

Results: MMP-2 level as well as TIMP-2 and TIMP-2 levels were significantly higher in patients with type 1 diabetes in comparison to the control group (p respectively <0,01; <0,02; <0,001). We observed higher MMP-9 level in obese patients than in patients with BMI value below 90 pc for sex and age (p<0,02). We noted lower MMP-2 level in patients with chronic complications and/or arterial hypertension (n=24) in comparison to patients without that kind of complications (p<0,05). Positive correlation between TIMP-1 level and HbA1c level was noted. Age of patients as well as BMI negatively correlated with MMP-2 and TIMP-2 and positively with TIMP-1. We observed a correlation between MMP-2, TIMP-2 and especially TIMP-1 with lipid levels. Strong positive correlation was noted between MMP-2 and TIMP-2 (r=0.8; p<0,0001).

Conclusions: 1. MMP-2, TIMP-1 and TIMP-2 levels are higher in patients with type 1 diabetes than in the control group. 2. Age, diabetes duration, metabolic control, BMI and lipids levels have influence on the MMPs/TIMPs system. 3. TIMP-1 is supposed to be the key marker of metabolic disturbances in type 1 diabetes.

Introduction: Sensitivity to insulin changes during puberty. It is necessary to distinguish physiological insulin resistance (IR) from pathological one. In children the IR index proposed by Belfiore (IRI(Belfiore)) could be used. Application of this formula is possible, when the reference values of the area under curve of glucose (GLU(AUC)) and insulin (INS(AUC)) concentration during oral glucose tolerance test (OGTT) are available for the studied population. Derivation of such reference values was the goal of this study.

Material and methods: Forty healthy children, aged 8-18.2 years, were enrolled in the study. Regarding the stages of puberty, the children were divided into 3 groups: A--stage I, B--stage II or III and C--stage IV or V. Serum glucose and insulin concentrations were measured for each child during OGTT and GLU(AUC) and INS(AUC) were calculated. The obtained mean values of GLU(AUC) and INS(AUC) for each group were used to calculate IRIBelfiore. To determine the cut-off point between physiological and pathological IR, receiver operating characteristic (ROC) analysis was performed for 40 studied children and 50 obese and insulin resistant children (according to QUICKY and/or elevated insulin concentration during OGTT), matched for age, sex and stages of puberty with the study group.

Results: The following mean values of GLU(AUC) and INS(AUC) were obtained in particular groups: A--189.3 mg/dL and 37.1 ulU/mL; B--207.4 mg/dL and 54.5 ulU/mL; C--188.8 mg/dL and 59.4 ulU/mL, respectively. The cut-off point value between physiological and pathological IR at the level 1.27 for IRI Belfiore was calculated.

Conclusions: 1. The mean values of GLU(AUC) and INS(AUC) obtained during OGTT could be used to calculate IRI Belfiore in children. 2. IRI(Belfiore) values above 1.27 indicate pathological IR in developmental age.

In this review we discuss contemporary opinions about the Leśniowski-Crohn disease in particular hormonal abnormalities including growth hormone resistance and the role of adipocytokines. The place of growth hormone in the treatment of chronic inflammatory bowel disease was also discussed.

Background: Turner's syndrome (TS) is one of the most common genetically conditioned diseases, its incidence amounting to one per 1900-2500 live female births. A marked short stature is a prime symptom of the disease, the average adult body height of untreated women being by 23 cm lower than that of healthy ones. According to Ranke, developmental disorders appear as early as in foetal life and are responsible for body length and mass deficits at birth in relation to gestational age.

Objectives: To revise present views regarding the course of physical development of girls with TS, especially at infancy and early childhood.

Material and methods: A total of 474 female newborns with Turner's syndrome were studied, the pregnancies, mostly second ones, not less than 38 weeks. Turner's syndrome was confirmed by chromosome analysis. Body mass at birth (BM) was related to the norms for gestational age (GA) designed by Usher and McLean.

Results: Growth disorders take place in TS since infancy, the growth rates in the age period of 2-3 years being similar to those observed in healthy population. After that period, however, growth rate in Turner girls steadily decreases as shown in percentile norms for TS. At the age of 6 years, the average difference in body height between Turner and healthy girls exceeds 1/3 of the final growth deficit noted in untreated adult women with TS.

Conclusion: We have demonstrated that body mass and length of Turner newborns were normal in relation to gestational age. Only in about 5% of newborns a simultaneous length and weight deficit exceeded -2 SD, and that deficit was attributed to intrauterine growth retardation (IUGR). In clinical practice, newborns without documented decrease in foetal growth rate, but having a pronounced body length deficit, are diagnosed as IUGR-afflicted. Since simultaneous body length and mass deficits were rare in our newborns, IUGR was regarded as unlikely in bringing about growth deficit in Turner girls. In about 1/5 of Turner newborns a weight or length deficit was found (19 and 1%, respectively). Since either of those deficits evidences intrauterine dystrophy (small for gestational age, SGA), the latter one should be considered much more frequent in TS than in the general population. Therefore, SGA appears to be one of the symptoms of TS and should thus be taken into account when explaining body mass and/or length deficit in female newborns. Growth disorders in foetuses with chromosomal aberrations typical of TS are, in all probability, as frequent as in those with normal both X-chromosomes.

Introduction: Type 1 diabetes is a known risk factor for arterial atherosclerosis. The first symptoms can be found even in childhood. The ultrasonographic measurements of intimal plus medial thickness in carotid arteries (IMT) and flow mediated dilatation (FMD) evaluated in brachial arteries, play a known role in the detection in these cases. The diabetes treatment intensification is an important factor in delaying early atherosclerotic changes. Currently, intensive treatment of children's diabetes with use of continuous subcutaneous insulin infusion with personal insulin pumps is gaining more and more popularity. THE AIM OF THIS STUDY was the evaluation of IMT and FMD indexes in children suffering from type 1 diabetes in the context of treatment intensification (multidose insulin injections v. personal insulin pumps).

Material and methods: We examined 64 children (29 boys and 35 girls) in the mean age 15.5 years treated with the multidose insulin injections method and 10 children using personal insulin pumps (4 girls and 6 boys) in the mean age 14.5 years. Using high resolution ultrasonography we evaluated IMT values in carotid arteries and FMD parameters in brachial arteries. In our analysis we estimated the blood concentration of lipid parameters, values of systolic and diastolic blood pressure, the age of diabetes onset, duration time of the illness and the values of HbA1c as a marker of metabolic control.

Results: We noticed significantly higher FMD values in patients treated with personal insulin pumps (13.7 vs. 5.5%, p=0.001). IMT values were similar in both groups (0.52 vs. 0.5 mm, p=0. 41). The level of HDL cholesterol was higher and triglycerides lower in the group with treatment intensification. The metabolic control was the same in both groups. In patients treated by the multidose insulin injections IMT correlated with systolic blood pressure values. We didn't notice any correlation between IMT and FMD in any group.

Conclusions: 1. Treatment intensification (personal insulin pumps) influences better vascular endothelial function in type 1 diabetic children and seems to be a significant tool in delaying the atherosclerotic process. 2. We need more examinations to explain the role of treatment intensification in common carotid arteries wall morphology in type 1 diabetic children. 3. The ultrasonographic detection of atherosclerotic changes in arterial vessels can help in the evaluation of the changes due to different methods of diabetes treatment.