Band 23, Heft 4

ABSTRACT Aldosterone plays an important role in blood pressure homeostasis, the regulation of circulating volume, and the maintenance of the sodium-potassium balance by binding to the mineralocorticoid receptor (MR). Primary aldosteronism (PA) states are associated with an increased cardiovascular risk, mediated not only by hypertension but also by the action of aldosterone in the modulation of vasodilation / vasoconstriction and oxidative stress. In this review, we discuss some of the cardiovascular actions of aldosterone and the most frequent causes of PA.

ABSTRACT The main aim of this study was to determine the extent to which physical activity and adiposity are associated with blood cholesterol levels in male adolescents. Anthropometric and physical fitness values were measured in all children. Body mass index (BMI) and physical activity index (PAI) were used to split participants into active overweight (ACO) and non-active normal-weight (NAN) groups. The cutoffs for the ACO group were BMI ≥ 22.6 kg/m 2 and PAI ≥ 3.5, respectively, whereas the corresponding cutoffs for the NAN groups were BMI < 20.0 kg/m 2 and PAI < 2. A total of 65 children (29 in ACO group, 36 in NAN group) were selected according to above criteria. ACO group showed significantly higher BMI and body fat as compared to their NAN counterparts ( p < 0.05). Adolescents from ACO group attained superior score for PAI and aerobic fitness ( p < 0.05). Most blood lipid variables were significantly lower in ACO group as compared to NAN ( p < 0.05) while HDL-cholesterol was higher in ACO group ( p < 0.05). There was significant positive correlation between HDLcholesterol and PAI in ACO group ( r = 0,38; p < 0.05). Physical activity index explained the majority of variance in HDL-cholesterol for ACO group (β = 0,513; p < 0.05). It seems that physical activity in adolescents is more important factor in balancing blood lipid status than adiposity per se , particularly for HDL-cholesterol.

ABSTRACT Overweight and diseases connected with it are increasing problems in children and adults. We often observe change of weight in thyroid disease. It is emphasized that changes in hormones such as peptide levels are in close relationship with regulation of body mass: ghrelin increases appetite and in effect increases body mass, but obestatin decreases appetite and weight. The aim of the study was to analyze the relationship between lipid-carbohydrate metabolism parameters and thyroid hormones and the level of gastric peptides (ghrelin & obestatin) in young patients with Graves' disease, Hashimoto's thyroiditis and in children with simple goiter. The study group formed 78 patients suffering from Graves' disease (29 girls and 2 boys; aged from 6 to 21 – mean 15,2 yrs) and Hashimoto's thyroiditis (29 girls and 3 boys; aged from 9 to 18 – mean 14,5 yrs). The control group consisted of children with simple goiter – 13 girls and 2 boys; aged from 9 to 18 – mean 14,8 yrs. In all patients, ghrelin and obestatin levels were analyzed by the RIA method (Phoenix Pharmaceuticals, USA). In children and adolescents with untreated Graves' disease we found higher levels of insulin and HOMA-IR index compared to the group of children with simple goiter (34±8 uIU/mL vs 15±5; p<0.03; 7.3±1.2 vs 3±0.3, p<0.03). No significant correlations were observed of gastric hormones with antithyroid antibodies, lipids or h-CRP in patients with untreated hyperthyroidism and subclinical hypothyroidism. Positive correlation was noted of insulin and glucose levels and HOMA-IR index with ghrelin level in children with newly diagnosed Graves disease (r=0.109, p<0.045; r=0.176, p<0.036; r=0.174, p<0.037). The correlation was also positive between obestatin level and HOMA-IR index in children with subclinical hypothyroidism in the course of Hashimoto's thyroiditis (r=0.497, p<0.011). We also examined the relationship between BMI, thyroid hormones and the level of gastric peptides. In untreated GD patients, ghrelin level exhibited a significant negative correlation with fT3 and fT4 (r=-0.38, p<0.041; r=-0.459, p<0.012) and positive with TSH (r=0.38, p<0.041) and BMI (r=0.8, p<0.01). In conclusion, we suggest that the disturbances in carbohydrate parameters in thyroid diseases have an essential effect on change of hormone-controlled appetite: ghrelin (in hyperthyroidism) and obestatin (in subclinical hypothyroidism).

ABSTRACT Background: GH excess predisposes to insulin resistance (IR). Obese subjects have blunted responses to GH stimulation and decreased spontaneous secretion. GH secretion has not been studied in the context of IR. Objective: To determine whether varying degrees of IR effects GH dynamics in obese children. Subjects/Design: Subjects (all > 10 y) were categorized according to gender and HOMA-IR to have either mild or severe IR. Twenty subjects (10 female) with mild IR completed the study, as did 18 (9 female) in the severe group. Each subject underwent a GH stimulation test with GHRH. GH peak and area under the curve (AUC) were compared between the groups. Results: Severe IR females had higher peak GH (mean±SD, 9.5±4.4 vs. 5.8±3.7 ng/dl, p=0.04) and trended toward higher GH AUC (356±207 vs. 221±128, p=0.06) than mild IR females. There were no differences in GH response in males, Conclusions: There may be a positive relationship between severity of IR and peak GH in obese girls.

ABSTRACT Background/Objective The identification of the different subtypes of amiodarone-induced thyrotoxicosis (AIT) may provide a rational basis for the choice of the appropriate medical treatment. The aim of this study was to evaluate differential diagnosis and treatment regimens of AIT in children and adolescent. Patients We reported 3 patients: A 6.7 years old boy with type I AIT a 17.9 years old girl with type II AIT and a 14.6 years old girl with mixed type AIT. Conclusions AIT is not an uncommon complication in countries with low iodine intake. AIT can be asymptomatic and can occur at any time in patients receiving amiodarone therapy. It is also very important to distinguish the type of AIT when planning therapy. Steroid therapy should be started when findings indicate type II or mixed-type AIT. Beta blockers may prevent heart thyrotoxicosis and recurrence of primary arrhythmia if amiodarone is discontinued.

ABSTRACT Leptin, adiponectin and resistin, mainly produced by adipocytes, play a major role in body weight regulation. Disturbances in the maintenance of normal body weight are found to occur also in thyroid diseases. There is a close relationship of the changes in thyroid hormones with the contents of adipose tissue and adipocyte-secreted proteins regulating energetic metabolism in the body. The study objective was to analyze the levels of leptin, adiponectin and resistin in children with untreated Graves' disease, subclinical hypothyroidism in Hashimoto's thyroiditis and in children with simple goiter. The study involved 78 patients with Graves' disease (29 girls and 2 boys, aged 6-21 years, mean 15.2) and with Hashimoto's thyroiditis (30 girls and 2 boys, aged 9-18 years, mean 14.5). The control group consisted of adolescents with simple goiter (13 girls and 2 boys, aged 9-18 years, mean 14.8). The levels of leptin, adiponectin and resistin were determined using the ELISA method (R&D System, USA). Patients with untreated Graves' disease showed higher adiponectin level than the subjects with hypothyroidism in Hashimoto's thyroiditis and in simple goiter (14.24±0.89 vs. 9.18±2.65, 10.15±2.5, p<0.007, p<0.01), but lower resistin level as compared to simple goiter and Hashimoto's thyroiditis (10.24±5.2 vs. 13.29±3.8, 12.2±2.8, p<0.01, NS). The analysis of leptin levels revealed no significant differences between children with subclinical hypothyroidism and untreated Graves' disease (4.42±0.87 vs. 3.1±0.45 NS). In conclusion, we suggest that disturbances in thyroid hormones in thyroid diseases have an essential effect on the levels of adiponectin and resistin released by adipose tissue.

SUMMARY Phenotypic presentation of 46,XY DSD depends on the underlying defects. Defect in androgen action on the target tissues or production of active metabolite share common morphological features. Molecular study may help differentiating these abnormalities with precision. Mutational analysis of androgen receptor ( AR ) and SRD5A2 genes was performed in 29 subjects with 46,XY DSD, by PCR-SSCP. The amplicons that showed an aberrant migration in SSCP were subjected to sequencing. Interestingly, six patients from 4 unrelated families (a pair of sibs, uncle/nephew and other two isolated) were identified with mutations in SRD5A2 gene. In five patients p.R246Q missense mutation was detected, of which four were homozygous and one was compound heterozygous: g.80_87delT CGCGAAG (p.A27fsX132) and p.R246Q. Another patient with isolated micropenis harbored a heterozygous p.G196S missense mutation. No AR gene mutation was detected. In conclusion, our study suggests that p.R246Q mutation is common amongst patients with SRD5A2 gene defect from the Northern states of India. Also, it records a novel deletion in exon 1 of SRD5A2 gene in a patient with severe hypospadias.

ABSTRACT Background/Aims : GH levels < 10 ng/ml in response to two different GH stimulation tests (GHSTs) are traditionally used to identify children with GH deficiency (GHD). Since GHSTs are imprecise, other diagnostic tools have been proposed. We assessed whether auxology, IGF-I and IGFBP-3 measurements followed by brain MRI and genetic analysis can replace the current diagnostic approach. Methods : Fifty-three children diagnosed with GHD by two different GHSTs. GH-1 gene was sequenced. Results : At presentation, 17% of patients were with height above -1.5 SD and 28% above -2.0 SD; 50% had IGF-1 concentration above -1.5 SD and 58% above -2.0 SD; 59% had pituitary anomalies demonstrated by MRI. Fourteen subjects harbored the heterozygous R183H mutation, one patient had the N47D mutation and one had a novel F25Y mutation in GH-1 . Using cut-off levels of -1.5 SD for height, IGF-I and IGFBP-3 excluded the diagnosis of GHD in 17, 68 and 79% of the children, respectively; a cut-off of -2 SD excluded 28, 88 and 96%, respectively. Further brain MRI and genetic tests excluded 81-96% and 96-100%, respectively, of children currently diagnosed with GH. Conclusion : Use of the tested approach, which avoids carrying out two GHSTs, would exclude most children currently diagnosed with GHD. Until better tools become available, we recommend identifying GHD in children by an integrated approach combining phenotype, auxological parameters, hormonal measurements and two separate GHSTs, with MRI and genetic tests to support the diagnosis.

ABSTRACT Background - Determination of body composition is an essential parameter in training athletes because low fat-muscle ratio might improve physical performance in many types of sports. Since training is often conducted in the field, it is important to determine whether simple field measurements of body composition assessment correlate with laboratory measurements. Objective - Examine the correlation of body fat content as measured using skinfold thicknesses (SF), air-displacement plethysmography (BOD POD), bioelectrical impedance analysis (BIA) and body mass index (BMI) age and gender adjusted percentiles. Method - Body mass as measured by SF, BOD POD, BIA, and BMI percentiles were examined in 29 elite, national team level, male and female volleyball players (age range 13 to 18) at the beginning of the training season. Results - Body fat percent measured by SF, BIA and BOD POD were highly positively correlated (r > 0.83). Measurements of body fat by SF, BIA and BOD POD were weakly correlated with BMI percentiles (r < 0.45). Conclusions - Results suggest that BMI percentile is not a good measure for body fat in adolescent elite male and female volleyball players. SF and measurements of body composition by BIA and BOD POD are essentially interchangeable.

ABSTRACT Diabetic autonomic bladder dysfunction is rare in the pediatric age group. An adolescent girl aged 16 years and 7 months, with type 1 diabetes mellitus since the age of 6 years, was diagnosed as having diabetic cystopathy. Ultrasonography of the urinary tract showed a distended bladder with normal kidneys. Laboratory evaluation revealed: normal serum urea, creatinine and electrolytes and elevated microalbuminuria. Urodynamic study demonstrated an impaired bladder sensation, increased cystometric capacity and detrusor arreflexia. Although more prevalent in adults and the elderly, autonomic bladder dysfunction must be considered in adolescents with type 1 diabetes mellitus.

ABSTRACT Very few abnormalities in endocrine function have been reported during long term gonadotropin-releasing hormone agonist (GnRHa) treatment in girls. Most authors agree that this therapy is safe and effective. We present an unusual outcome of long term GnRHa therapy in two girls with central precocious puberty(CPP) of idiopathic or organic origin. They have received monthly depot injections of triptorelin acetate for a time period of 8 years. Thyroid function was examined by measuring serum levels of thyrotropin (TSH), thyroxine (T4), thyroid antibodies, and ultrasound of the thyroid gland. One of the girls was at the age of 8.5 years, having elevated thyroid antibodies, mild goitier and an abnormal ultrasound of the thyroid gland, suggesting autoimmune thyroiditis. Another girl with a hypothalamic hamartoma developed diabetes mellitus at the age of 9 years. Both of these girls were early diagnosed for CPP, at 6 months and 8 months respectively, and given GnRHa treatment. So far, it is not known whether these autoimmune diseases are related to the GnRHa treatment or are simply a coincidence. However, we suggest a closer monitoring of girls with CPP who have had a long period of treatment.

ABSTRACT Growth Hormone (GH) is a 22 kDa protein that has effects on growth and glucose and fat metabolisms. These effects are initiated by binding of growth hormone (GH) to growth hormone receptors (GHR) expressed in target cells. Mutations or deletions in the growth hormone receptor cause an autosomal disorder called Laron-type dwarfism (LS) characterized by high circulating levels of serum GH and low levels of insulin like growth factor-1 (IGF-1). We analyzed the GHR gene for genetic defect in seven patients identified as Laron type dwarfism. We identified two missense mutations (S40L and W104R), and four polymorphisms (S473S, L526I, G168G and exon 3 deletion). We are reporting a mutation (W104R) at exon 5 of GHR gene that is not previously reported, and it is a novel mutation.

ABSTRACT We described the case of an infant with nephrogenic diabetes insipidus (NDI) with a novel mutation in the arginine vasopressin receptor 2 ( AVPR2 ) gene. A 1-month-old infant showed failure to thrive and hypernatremia. The water deprivation test revealed elevated serum osmolality and low urine osmolality. The patient showed a slight but not significant response to intramuscular injection of arginine vasopressin (AVP). DNA analysis revealed a novel missense mutation involving substitution of proline for leucine at position 173 (P173L), which was reported to be important for stabilizing the hydrogen bond between tyrosine at position 205 and leucine at position 169. This mutation was not detected in 116 ethnic-matched controls. This case, with clinical data including the water deprivation test and P173L mutation, will facilitate understanding the structure and function of the AVPR2.

ABSTRACT Paragangliomas are extradadrenal neuroendocrine tumors, recently associated with gene mutations in the succinate dehydrogenase complex (SDH). These mutations are thought to be responsible for the familial paraganglioma syndrome. Average age of tumor diagnosis for SDH mutation carriers is about 30 years of age, but patients younger than 10 years have been reported. We present the case of a 13 year-old boy with abdominal paraganglioma, whose mother also had a history of thoracic paraganglioma diagnosed at 14 years of age. Both were found to carry a mutation in exon 4 of the SDHB gene, heterozygous for c.418G>T, p.Val140Phe sequence. Compared to the other SDH subtypes, SDHB associated tumors have been found to be much more aggressive. This has led to current recommendations that tumor screening of asymptomatic SDHB carriers should start as early as 10 years of age. An even earlier initiation seems warranted for the identified carriers in this family.