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

Introduction: Higher frequency of autoimmune diseases in patients with Turner's syndrome (TS) compared with the general population has been described. 5 to 10% of cases occur before adolescence. The goal of the study was to determine the prevalence of thyro-peroxidase antibodies (TPO-Ab) in correlation with karyotype, clinical symptoms and hormonal thyroid function in TS patients.

Material and methods: 96 girls with TS, aged 0.5-19.8 years (mean age 12.3+/-5.0) and 58 girls matched for age and BMI (control group) were analysed. The diagnosis of TS was established basing on clinical features and karyotype analysis. 54 had X monosomy, 7--isochromosome, 1--other X chromosome aberration, 11--mosaicism 45,X/46,XX, 3--45,X/47,XXX, 1--45,X/46,XX/47,XXX, 19--mosaicism with structural aberration: 12--45,X/46,X,i(Xq), 2--others, 5--with Y chromosome. In all children TSH, FT(4), FT(3), TPO-Ab, cholesterol, triglyceride levels, physical and ultrasonographic examination were performed.

Results: 25% of TS patients were positive for TPO-Ab. This frequency was significantly higher (p=0.0017) than that seen in the control group (5.2%). Positive titers of TPO-Ab were found: in 42% of girls with isochromosome (46,X,i(Xq) and 45,X/46,X,i(Xq)), 22.2% with X monosomy, and 17.4% with other karyotypes. The percentage of positive TPO-Ab titres increased with cumulative age of TS patients. It was 6.7% at the age of 10 years and almost doubled (12.1%) one year later. The next strong increase was observed at the age of 16 (up to 19.1%) and gradually rose to 20 years of age. Mean age of seronegative patients was significantly lower than that of seropositive patients (p=0.018). Only 2 patients manifested symptoms of hyperthyroidism requiring short period of antithyroid treatment. Others did not reveal any clinical features of thyroid dysfunction, although developed thyroid abnormalities such as elevated TSH (11.4%) or goiter (28%). Lack of correlation between TPO-Ab, thyroid hormones and lipid levels was associated with L-thyroxine supplementation, in patients with mildly elevated TSH, prior to the study.

Conclusions: Patients with TS, especially with isochromosome, have antithyroid antibodies more frequently than their co-evals. Therefore, it is important to monitor TPO-Ab from about the age of 10 years even in asymptomatic patients. However, in routine clinical practice, both the thyroid examination and TSH level (even in asymptomatic patients) should be screened yearly for early detection of subclinical hypothyroidism and risk of more severe growth retardation in girls with TS.

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.

Background: Constitutional delay of growth and puberty (CDGP) is a variant of normal pattern of growth and development with strong familial impact. THE AIM of the study was to assess the influence of birth weight and length, parents' height, boys height and bone age at the age of 14-16 years and mutation age on their final height.

Material and methods: In 69 boys in the mean age of 14.9+/-1.2 years, whose height fell below the 3rd percentile, CDGP was diagnosed. After completion of growth (at the age of 22.6+/-3.5 years) correlations of different parameters with final height were estimated.

Results: Statistically significant correlation between birth weight, parents' height, mutation age and final height was observed, but no association between birth length, height and bone age in the age group of 14-16 years and the final height was found.

Conclusions: Adult height of boys with CDGP is directly proportional to birth weight, mutation age and parents' height.

Introduction: Despite that numerous investigations on the nature of diabetic microangiopathy were carried out, its pathomechanism remains unclear.

Objective: The aim of the study was to analyze the relation between early diabetic microangiopathy and the proinflammatory cytokines, NAG and its A and B isoforms in blood and urine in children diagnosed with diabetes mellitus type 1.

Material and methods: The study was carried out on the group of 56 children with diabetes mellitus 1 (age 13.6+/-3.74) and 35 healthy children selected as the controls. All the patients had 24 hrs albuminuria, HbA1c, C-peptide as well as the NAG enzyme and its A and B isoforms serum and urine activities measured. Additionally, all the children had TNF-a and IL6 level in serum measured. Each patient had 24 hrs blood pressure monitored and underwent ophthalmologic examination.

Results: Children with long-standing diabetes mellitus and retinopathy (group 1, n=15) were older and were characterized by a statistically significant longer duration of the disease and higher HbA1c level in comparison with the patients who presented with no sign of diabetic retinopathy (group 2, n=41). In the group 1 statistically significant higher TNF-alpha serum level (p=0.01), NAG (p=0.002) and its isoforms A (p=0.007) and B (p=0.001) urine activities were measured in relation to the group 2. Additionally the level of IL-6 and NAG and its isoforms A and B serum activities were higher in group 1 than in group 2, however the differences were of no statistical significance. Moreover the children from group 2 in comparison with the healthy controls showed statistically significant higher TNF-alpha serum activity (p=0.016) and NAG (p<0.001) and its A (p<0.001) and B (p<0.001) isoforms both serum and urine activities.

Conclusions: The occurrence of the detectable serum TNF-alpha activity in children with diabetes mellitus type 1 showing no sign of diabetic retinopathy and nephropathy and no microalbuminuria with the concomitant increase of NAG and its isoforms serum and urine activities might point toward prompt occurrence of these changes in the eye and the kidneys.

Background: Children born with a history of Intra-Uterine Growth Retardation (IUGR) may be susceptible for reduced growth velocity and growth deficiency. The causes of GH/IGF-1 resistance are unknown. Klinefelter syndrome is characterized by excessive growth, resulting from hypogonadism, open bone age and a prolonged growth.

Objectives: The case of a 6-year-old boy with Klinefelter syndrome born with IUGR and deep growth deficiency was studied.

A case report: A 6-year-old boy with birth weight 2300 g born of term in 38 Hbd is presented. The cariotype was 47XXY. The phenotype was typical for a child with IUGR. GH in the clonidin test was 37.4 microIU/ml, IGF-1 -- 111 ng/ml. Increased IGF-1 level from 178.1 ng/ml to 360.9 ng/ml was founded in the IGF-1 generation test.

Conclusions: The cause of growth deficiency in this case could be GH/IGF-1 resistance.

Background: Increased risk of atherosclerosis in individuals with diabetes mellitus is not fully explained by the conventional risk factors. Therefore, new independent risk factors are taken under consideration. AIM OF THE STUDY was to evaluate selected risk factors of atherosclerosis in children with type 1 diabetes mellitus and hypercholesterolemia.

Material and methods: The study comprised 30 diabetic children, aged 5-18 years with plasma cholesterol concentration exceeding 170 mg/dl. In children, their parents and siblings plasma concentration of total cholesterol, HDL and LDL-cholesterol, triglicerides, homocysteine, apolipoprotein A-I, apolipoprotein B was measured and electrophoretic distribution of lipids was performed. Anthropometric measurements with BMI estimation were performed in diabetic children. Data were analyzed with respect to BMI, metabolic control and physical activity in children and with respect to family history of atherosclerosis.

Results: No significant differences in measured parameters were found between diabetic children and their healthy siblings besides significantly lower homocysteine concentration (p=0.037). Concentration of triglicerides was significantly higher in children with low than with high physical activity (101.6+/-64.6 mg/dl vs. 60.2+/-27.4 mg/dl respectively, p<0.05), HDL cholesterol was significantly lower in children with poor than with a satisfactory metabolic control (58.3+/-10.0 mg/dl vs. 69.1+/-12 mg/dl, p<0.05) and lipoprotein apoB concentration was significantly higher in children with positive (0.77+/-0.15 g/l) compared to children with a negative family history of atherosclerosis (0.66+/-0.09 g/l, p<0.05). Overweight did not influence the measured parameters significantly. Statistically significant positive correlations were found for apoB between affected children and their mothers (r=0.62), for LDL-cholesterol between affected children and their fathers (r=0.35), and for total cholesterol (r=0.47) and homocysteine (r=0.44) between affected children and their siblings.

Conclusions: 1. Lipid disorders in children with type 1 diabetes mellitus may be present regardless their metabolic control, but they are more pronounced in children with poor control 2. Higher triglicerides concentrations were found in children with low physical activity and higher apolipoprotein B concentration in children with a positive family history for atherosclerosis. 3. Parental lipoprotein concentration may significantly influence the lipid profile in their diabetic offspring.

Background: The elevated blood pressure is one of the most important risk factors of diabetic micro- and macroangiopathy.

Aim of the study: Evaluation of the prevalence of prehypertension and relationship between prehypertension, metabolic control and chronic complications in children and adolescents with type 1 diabetes mellitus.

Materials and methods: 83 patients aged 12.0-18.9 years, with a duration of diabetes 0.5-17.3 years, without evidence of arterial hypertension were recruited. In all patients 24-hour automatic blood pressure monitoring was performed with oscillometric device. The individuals with >40% of systolic and/or diastolic blood pressure >120/80 mmHg were defined as prehypertensive. HbA(1)c was measured by HPLC, plasma lipid levels--by an enzymatic method and urinary albumin excretion rate by chemiluminescent enzyme immunoassay method. Body mass index (BMI) and daily dose of insulin were calculated. Ophthalmoscopic examination and power spectral analysis of heart rate variation were performed.

Results: In 30 individuals (36.1%) prehypertension was diagnosed. The prehypertension group had older age (17.5+/-1.1 vs. 15.9+/-2.3 years; p<0.001) and longer duration of the disease (7.3+/-4.7 vs. 4.7+/-3.4 years; p=0.005) as compared with the group with normal blood pressure. There were no significant differences between groups in HbA1c, daily dose of insulin, BMI-SDS, lipids profile, prevalence of microalbuminuria and retinopathy. In the patients with prehypertension the a greater activity of sympathetic activation was observed (LF/HF: 1.00+/-0.06 vs. 0.78+/-0.04, p=0.018).

Conclusions: Prehypertension is frequently recognized in type 1 diabetic children and adolescents. The prevalence of prehypertension is associated with older age, longer duration of diabetes and the shift of the sympatho-vagal balance toward sympathetic activation. There is no relationship between prehypertension and metabolic control or the prevalence of microvascular complications.

Adenomas of the hypophysis are tumors of the CNS which are on the third place in the frequency of appearance, which cause disturbances of hypophyseal function. In children incidentaloma is seldom observed. The authors present a 16-year-old girl who was admitted to the clinic because of amenorrhoea and an increased growth velocity during the last year. The MRI examination of the hypophysis proved a hypophyseal adenoma. Hormonal laboratory examinations do not show any hormonal activity of the observation. The girl's case is presented because the diagnosis of an incidentaloma is exceptionally rare in this age group.

Introduction: Matrix metaloproteinases (MMPs) have been implicated in various pathological processes including inflammatory response, atherosclerosis and cardiovascular disease. Growth hormone deficiency (GHD) is associated with prematury atherosclerosis and cardiovascular disease. Circulating levels of matrix metaloproteinases and their tissue inhibitors (TIMPs) so far have not been assessed in children and adolescents with GHD.

Material and methods: Serum levels of matrix metaloproteinase 2 (MMP-2), matrix metaloproteinase 9 (MMP-9) and tissue inhibitor of metaloproteinase 2 (TIMP-2) were measured in 44 (11 girls and 33 boys) children and adolescents with newly diagnosed GHD [age (mean+/-SD) 12.5+/-2.7 years, height 1.3+/-0.1 m, body surface area (BSA) 1.1+/-0.2 m(2) and body mass index (BMI) 17.4+/-2.2 kg/m(2)] and in 32 (11 girls and 21 boys) healthy children and adolescents (age 12.4+/-2.9 years, height 1.6+/-0.2 m, BSA 1.4+/-0.3 m(2) and BMI 18.7+/-2.6 kg/m(2)). Human MMP-2, MMP-9 and TIMP-2 measurements were carried out with the use of ELISA kits.

Results: Patients with GHD had significantly higher concentrations of MMP-2 (287.2+/-60.5 vs. 235.8+/-41.3 ng/ml, p<0.0001) and TIMP-2 (81.4+/-14.9 vs. 62.7+/-15.9 ng/ml, p<0.0001) levels than the control healthy group. There was no difference in MMP-9 levels (338.5+/-197.9 vs. 276.3+/-121.7 ng/ml, p=0.12) between patients with GHD and controls.

Conclusions: Children and adolescents with GHD have elevated serum concentrations of MMPs-2 and TIMP-2.

Introduction: The late complications of diabetes consisted of autonomic neuropathy, nephropathy, which more often coexist with hypertension in children with type 1 diabetes mellitus. THE AIM OF THE STUDY was to assess the connections between changes in the autonomous nervous system, 24-hour ABPM and daily albumin excrection in children with hypertension and type 1 diabetes mellitus.

Material: The group consisted of 72 patients with diabetes (diabetes duration time 6.5+/-1.5 years). 34 patients of that group have hypertension. The control group consisted of 30 healthy children matched according to age and sex.

Results: In children with hypertension we found significantly often occurrence of microalbuminuria (13/34 i 1/38, p<0.001). In 17 patients from the group with hypertension and 17 patients without hypertension we affirm signs of autonomic neuropathy. The values of heart rate variability (HRV) were significantly decreased in the group with hypertension as compared to the control group. A stepwise multiple regression analysis with hypertension as a dependent variable and diabetes duration time, microalbuminuria, HbA1c level, HRV parameters and a presence of autonomous neuropathy as predictors proved that hypertension is associated with higher HbA1c level (b=0.35), the presence of autonomous neuropathy (b=0.28), and lower HF values (b=0.41) (p<0.01).

Conclusions: Hypertension in children with type 1 diabetes mellitus is correlated with the presence of autonomous neuropathy, higher HbA1c level and lowered values of heart rate variability parameters.