Relationship between intestinal hyperpermeability and obesity / Összefüggés a bél-hiperpermeabilitás és az elhízás között

Obesity is a combination of genetic, environmental factors, and systemic inflammation of adipose tissue. In the last decade, more and more evidence suggests that intestinal microbiota is an environmental factor that plays a crucial role in obesity and associated metabolic disorders. Here, we review the association between intestinal microbiota and obesity based on the literature data available to us. The intestinal flora, in the equilibrium state of conventional bacteria, protects the health of the host and helps the development of the immune system. The genome, diet, lifestyle, and epigenetic changes of the host can pathologically alter the composition of the microbiota. In dysbiosis, the development of the gut-associated lymphoid tissue (GALT) associated with the intestinal tract is impaired and the integrity of the intestinal barrier is impaired. Due to the consequent intestinal hyperpermeability, components of pathogenic pathogens such as lipopolysaccharides enter the bloodstream. These components bind to receptors on adipose tissue immune cells as ligands for molecular samples with pathogenic properties and induce adipose tissue dysfunction. The secretion of inflammatory cytokines in adipose tissue is increased. This induces persistent low chronic inflammation, which is responsible for the development of obesity. The damage to health caused by the hyperpermeability of the intestinal barrier can be reduced by interventions, or restored early in the process. Knowing the relationships will help prevent and treat obesity.

Pregnancy in women with cystic fibrosis: 14 case reports and literature review / Cystás fibrosisban szenvedo nok várandóssága: 14 eset ismertetése és irodalmi áttekintés

Összefoglaló. A cystás fibrosisban szenvedo betegek várható élettartama jelentosen megnott az utóbbi évtizedben, egyre több beteg képes saját gyermeket vállalni. Célunk a cystás fibrosisban szenvedo várandós nok perinatalis és anyai történéseinek felmérése saját eseteink és az irodalmi adatok alapján. 14, cystás fibrosisban szenvedo no 16 várandósságáról számolunk be. Rögzítettük a várandósok életkorát, testtömegét, testmagasságát, testtömegindexét, légzésfunkciós értékeit a graviditás kezdetén és végén. Az anyai átlagéletkor szüléskor 21,6 (18-25) év volt. Az anyák graviditásának kezdetén a testmagasság átlaga 162 (150-175) cm, a testtömeg átlaga 57,6 (42-72) kg, a testtömegindex átlaga 21,4 (19,1-23,2) kg/m2 volt. A graviditás végén a testtömeg átlaga 62 (39-76) kg, a testtömegindex átlaga 23,6 (21,3-24,1) kg/m2 volt. A graviditás alatti súlygyarapodás átlaga 8 (1,5-21,5) kg volt. A légzésfunkciós értékek a graviditás kezdetén 2 betegnél voltak beszukültek. A graviditás alatt még 2 beteg légzésfunkciós értékei csökkentek. A sikeres graviditások száma 13 volt. 1 anya kétszer szült. A koraszülések száma 1 volt. A várandósság átlagosan a 38. (34-40.) gestatiós hét után 7 esetben császármetszéssel, 6 esetben hüvelyi szüléssel fejezodött be. A vetélések száma 3 volt. Az Apgar-pontszám minden esetben normális volt. 13 gyermek közül 11-nél a verejtékteszt nem volt emelkedett. 2 gyermeknél magas verejtékértékek voltak, egyikük c.1521_1523delCTT-heterozigóta, a másiknál génmutációt nem tudtunk igazolni. A cystás fibrosisban szenvedo nok általában jól tolerálják a várandósságot az esetek többségében. A kórosan beszukült tüdofunkcióval, alacsony tápláltsági állapottal és cukorbetegséggel rendelkezo nok nagyobb valószínuséggel számíthatnak káros következményekre. Az újszülöttek prognózisa általában jó, de számítani kell a koraszülés és a kis súllyal születés gyakoribb elofordulására. Ideális esetben a várandósságot elozetes tanácsadás útján kell megtervezni, és speciális cystás fibrosis csoportnak kell a várandósok ellátását figyelemmel kísérni, ideértve a cystás fibrosis kezelésében jártas szülészeket is. Kisszámú saját adatunk retrospektív elemzése megerosíti az irodalmi adatok tanúságait. Orv Hetil. 2021; 162(28): 1129-1136. Summary. The life expectancy of patients with cystic fibrosis has increased significantly in the last decade, with more and more patients being able to have their own children. The aim of our study was to assess the perinatal and maternal outcome of pregnant women with cystic fibrosis based on our own cases and literature data. We report 16 pregnancies in 14 women with cystic fibrosis. We recorded the age, body weight, height, body mass index, and respiratory function values of pregnant women at the beginning and end of pregnancy. The mean maternal age at childbirth was 21.6 (18-25) years. At the beginning of maternal pregnancy, the mean height was 162 (150-175) cm, the mean body weight was 57.6 (42-72) kg, and the mean body mass index was 21.4 (19.1-23.2) kg/m2. At the end of pregnancy, the mean body weight was 62 (39-76) kg and the mean body mass index was 23.6 (21.3-24.1) kg/m2. The weight gain under pregnancy was mean 8 (1.5-21.5) kg. The respiratory function values at the onset of pregnancy were narrowed in 2 patients. During pregnancy, the respiratory function values of 2 more patients decreased. The number of successful gestations was 13. A mother gave birth twice. The number of premature births was one. The pregnancy after the mean 38. (34-40.) gestational week was completed in 7 cases by cesarean section and in 6 cases by vaginal delivery. The number of miscarriages was 3. The Apgar score was normal in all cases. In 11 of 13 children, the sweat test was not elevated. 2 children had high sweat values, one of them is heterozygous with c.1521_1523delCTT, the other could not prove a gene mutation. Women with cystic fibrosis generally tolerate pregnancy well, in most cases. Women with poor lung function, low nutritional status, and diabetes are more likely to expect adverse consequences. The outcome of the newborns is good in general, but a common occurrence of premature birth and low birth weight is to be expected. Ideally, pregnancy should be planned through prior counseling and the care of pregnant women should be monitored by a specialized cystic fibrosis team, including obstetricians experienced in the treatment of cystic fibrosis. A retrospective analysis of our own small-number data confirms the evidence from the literature data. Orv Hetil. 2021; 162(28): 1129-1136.

[Neuroendocrine mechanisms controlling the development in puberty. A literature overview]. / A pubertas fejlodését szabályozó neuroendokrin mechanizmusok. Irodalmi áttekintés.

Puberty is the stage of development in human life, when the hypothalamus-hypophysis-gonad axis is re-activated after quiescence. Humanity has long been concerned with the idea of exogenous and endogenous factors and mechanisms that influence the temporal course of puberty neuroendocrine events. Recent discoveries have helped to understand the functioning of the neuroendocrine system. It has been clarified that kisspeptin plays a key role in puberty and regulation of fertility. However, in the function of the gonadotropin-releasing hormone (GnRH) pulse secretion, besides kisspeptin, neurokinin B, dynorphin neurons other positive and negative signals are involved, guiding the release of hormones of hypophysis gonadotropin. The knowledge of these nerves further enhanced the understanding of GnRH pulsation modulation by endocrine, metabolic and environmental impacts. The authors point out the risk of endocrine disruptors in the physiological course of puberty. The aim of the review is to provide a comprehensive picture of the research results of the physiology of kisspeptin, as the manipulation of kisspeptin signaling has the potential for novel therapies in patients with pathologically low or high luteinizing hormone (LH) pulsatility. Orv Hetil. 2018; 159(29): 1175-1182.

[Relationship of infant feeding on childhood obesity. A literature review]. / A csecsemokori táplálás összefüggése a gyermekkori elhízással. Irodalmi áttekintés.

The increasing frequency of childhood obesity is a serious public health concern. Today it is recognized that the infant feeding during critical periods of early human development ("the first 1000 days") can be a long-term impact for future health. Authors deal with with the infant period of the first 1000 days of life starting from the conception, based on literature review. Since 2010 a large number of publications have appeared in which the relationship between infant feeding, early weight gain and later obesity are investigated. The majority of studies have demonstrated, that breastfeeding has a marked effect on early growth and reduces the risk of obesity in the long-term. The health benefits of breastfeeding over infant formula feeding are accepted, however, the relationship between infant feeding and later obesity, there is no clear consensus in the literature. The authors investigated this contradiction reviewing the newly published articles over the last few years. In summary they established, that duration of breastfeeding for at least 4 months have an important role in lowering of childhood adiposity risk. The different or ambiguous statements in the relevant publications can be explained by the fact that the development and the prevention of obesity are multifactorial. Orv Hetil. 2017; 158(24): 938-943.

[Metabolic complications of obesity during adolescence, particularly regarding elevated uric acid levels]. / Az elhízás anyagcsere-szövodményei serdülokorban, különös tekintettel az emelkedett húgysavszintek elofordulására.

INTRODUCTION: Obesity is a social problem worldwide that leads to several diseases, including metabolic syndrome, hypertension and cardiovascular diseases. It is known that hyperuricemia in adults may be associated with these disorders. AIM: The aim of the authors was to investigate the frequency of metabolic syndrome and hyperuricemia and their relationship among obese adolescents. METHOD: This was a cross-sectional study. The authors analysed the data of 162 overweight or obese adolescents (100 boys and 62 girls) who were previously investigated in a paediatric endocrinology consultation. Anthropometric and metabolic parameters were evaluated in all subjects. Healthy, age-matched, non obese girls (n = 20) and boys (n = 26) were used as controls. The age of overweight or obese boys was: 12 ± 2.1 and overweight or obese girls was 11 ± 2.5 years. In the control group the age of boys was 12.9 ± 2.5 years and the age of girls was 13.2 ± 1.6 years. Linear regression was used to evaluate associations between uric acid and clinical and laboratory findings associated with metabolic syndrome. RESULTS: Obese or overweight subjects had greater BMI SDS (boys, 3.4 ± 1.3 vs 0.05 ± 0.4 in controls, p<0.0001; girls, 3.75 ± 1.4 vs 0.72 ± 0.9 in controls, p = 0.0001), waist circumference (boys, 90.1 ± 9.2 vs 82.3 ± 6.4 cm in controls; girls, 90.2 ± 8.6 vs 78.1 ± 7.2 cm in controls, p<0.001), higher systolic blood pressure (boys, 125 ± 14.3 vs 118.2 ± 10.8 mmHg in controls, p = 0.02; girls, 125.8 ± 11.8 vs 119.8 ± 8.8 mmHg in controls, p<0.01), diastolic blood pressure (boys, 78.4 ± 9.1 vs 71.2 ± 8.0 mmHg in controls, p = 0.0003; girls, 76.45 ± 7.2 vs 73.2 ± 6.3 mmHg in controls, p = 0.0453). The prevalence of metabolic syndrome was 45/162 (27.8%) and the prevalence of hyperuricemia was 62/162 (38.3%). Of the 45 subjects with metabolic syndrome, 30 (66.7%) had hyperuricemia. CONCLUSIONS: It can be concluded that hyperuricemia is strongly associated with metabolic syndrome. The high concentration of uric acid predicts cardiovascular risk in adulthood. It is important for paediatricians to determine and assess uric acid levels in overweight or obese adolescents.

[Questions and dilemmas in the management of hypospadias]. / A hypospadiasis ellátásában felmerülo kérdések, dilemmák.

Hypospadias is the second most common congenital malformation in males. Etiology remains unknown in about 70% of the cases. Distal hypospadias is considered not only developmental abnormality of the urethra in males, but it may also constitute a mild form of sexual development disorder in 46,XY males. Most urologists and endocrinologists consider that it is necessary to perform a detailed investigation of children presenting with proximal hypospadias associated with a small phallus or poorly developed scrotum and undescended testes. Currently, there is no generally accepted recommendation for the preoperative evaluation of hypospadias and, therefore, masculinizing surgery without preoperative evaluation is performed in these children. The authors summarize the international literature data and their own experience for the assessment and management of hypospadias concerning questions and problems related to preoperative investigation, masculinizing surgery and additional surgery. A detailed algorithm is presented for preoperative evaluation of both proximal and distal hypospadias.

[Prevalence and possible causes of hypospadias]. / A hypospadiasis gyakorisága és lehetséges okai.

Hypospadias is the most common congenital malformation of the male external genitalia. After the heart and circulatory system, it is the second most common developmental disorder in males. It is due to a midline fusion defect of the male urethra, which results in a misplaced urethral meatus. Hypospadias may be distal, medial and proximal. It may occur as an isolated defect or it may develop together with other genital disorders (retention of testes in one or both sides, microphallus, bifid scrotum) or with malformation of other organs. In some cases syndromic forms may also occur. Genetic factors play a crucial role in the occurrence of early developmental defect, but endocrine and environmental factors may also be important in the aetiology of hypospadias. It may be associated with various sex and autosomal chromosomal abnormalities. Monogenic and chromosomal causes of hypospadias accounts for about in 30% of all cases, while genetic factors remain unknown in 70% of cases. The authors summarize the development of the male external genitalia, the prevalence and possible causes of hypospadias. They propose that better understanding of the pathogenesis of the disease may contribute to the prevention and decreased prevalence of the disease.

[Obesity, hormonal and metabolic abnormalities in adolescent girls with polycystic ovary syndrome]. / Elhízás, hormonális és anyagcserezavarok serdülokori polycystás ovarium szindrómában.

INTRODUCTION: Polycystic ovary syndrome is associated with metabolic abnormalities, such as dyslipidemia, obesity, glucose intolerance, which are also components of the metabolic syndrome. Central obesity and insulin resistance appear to play an important role in the pathogenesis of polycystic ovary syndrome, perhaps via subsequent steroidogenic dysregulation. AIM: The aim of the authors was to assess metabolic and hormonal abnormalities in adolescent girls with polycystic ovary syndrome. METHOD: The study included 52 adolescents diagnosed with polycystic ovary syndrome based on the Rotterdam criteria. Anthropometric, hormonal and metabolic parameters were evaluated among all subjects. 20 healthy, age-matched, non-obese, regularly menstruating girls were used as controls. Of the 52 patients, 15 patients were born with low-birth-weight and 37 patients were born with normal birth weight. Oral glucose tolerance test was performed in all patients and controls. The age of patients was 16.8±3.1 years, and the age of controls was 16.95±2.1 years. RESULTS: Among patients with polycystic ovary syndrome the prevalence of overweight and obesity was 35% (n = 18), while impaired fasting glucose occurred in one patient, impaired glucose tolerance in 8 patients, insulin resistance in 25 patients and metabolic syndrome in 12 patients. Serum triglyceride levels in patients and controls were 1.4±0.8 and 0.9±0.3 mmol/l, respectively (p<0.05), while fasting blood glucose, total cholesterol, HDL and LDL cholesterol were not different in the two groups. Metabolic abnormalities and obesity were more severe and more frequent in patients with low-birth-weight compared to those born with normal weight. There was a negative correlation between birth weight and body mass index SDS values and a positive correlation between fasting insulin levels and body mass index SDS (r = 0.37) in patients born with low-birth-weight. CONCLUSIONS: Abnormal glucose metabolism is frequently present in adolescents with polycystic ovary syndrome. It is possible that early diagnosis of polycystic ovary syndrome in adolescence may prevent some of the long-term complications associated with this syndrome.

[Role of genetic and environmental factors in the development of polycystic ovary syndrome]. / Genetikai és környezeti tényezok hatása a polycystás ovarium szindróma kialakulására.

Polycystic ovary syndrome is the most common heterogeneous endocrine abnormality in women in the reproductive age. The syndrome remains an enigmatic disorder because the aetiology is still unclear. Familial aggreagation is relatively common among patients with polycystic ovary syndrome suggesting a significant genetic component, although the way of inheritance has not been established firmly. The authors review the relevant medical literature and suggest that genetic and environmental factors play a role in the development of polycystic ovary syndrome. To date, no gene has been identified that causes or contributes substantially to the development of a polycystic ovary syndrome phenotype. Polycystic ovarian syndrome is considered to be an oligogenic disorder in which the interaction of a number of genetic and environmental factors determines the heterogeneous clinical and biochemical phenotype. To summarize current evidence the authors conclude, that when we are able to identify and then modify environmental determinants, then we will be able to safeguard better the health of those patients who are predisposed to disease development due to genotype or previous environmental effects.

[Diagnostic difficulties of polycystic ovarian syndrome in adolescent girls]. / A serdülokori polycystás ovarium szindróma diagnosztikai nehézségei.

Polycystic ovary syndrome is a heterogeneous disorder characterized by chronic ovulatory dysfunction and hyperandrogenism. It occurs in 6-8% of the female population in the reproductive age. The syndrome may be associated with various metabolic disorders which may impair the quality of life and life expectancy of patients. The diagnosis in adults is usually established by the presence of three criteria. Polycystic ovary syndrome can be also identified in adolescent girls. Although the clinical, hormonal and metabolic features are similar to those found in adult women, it may be difficult to distinguish normal adolescents from those with polycystic ovary syndrome. Irregular menstruation, anovulatory cycles, and acne are not uncommon in adolescents, and polycystic ovary syndrome may mimic physiological anovulation in adolescents. There is a high probability of polycystic ovary syndrome if anovulatory cycles persist for more than 2 years. The diagnosis of polycystic ovary syndrome in adolescents may require a unique set of criteria, however, there are no generally accepted recommendations for the diagnostic work-up. The authors propose that hyperandrogenemia is often the most reliable finding in this age group, and it may be prudent to define adolescent polycystic ovary syndrome according to the Rotterdam consensus criteria. Obesity in adolescent girls may increase the severity of symptoms of polycystic ovary syndrome and this underlines the importance of early diagnosis and treatment.

[Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome]. / Peripubertális petefészekciszta-torzió mint a fel nem ismert polycystás ovarium szindróma korai szövodménye.

The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

[Effect of treatment with gonadotropin releasing hormone analogues in girls with idiopathic central precocious puberty]. / Az idiopathiás centrális pubertas praecox gonadotropin releasing hormon analóg terápiájának hosszú távú hatása leányoknál.

UNLABELLED: It has been proven for more than two decades that gonadotropin releasing hormone analogue therapy is the only choice of treatment in patients with central precocious puberty. AIMS: The aim of the authors was to assess the effect of gonadotropin releasing hormone analogue treatment on final height, body mass index, bone mineral density and ovarian function in girls with idiopathic central precocious puberty. METHODS: Predicted adult height, target height and achieved height due to therapy was assessed in 15 girls with idiopathic precocious puberty treated with gonadotropin releasing hormone analogue. At the beginning of the treatment, the age of the girls was 7.0±0.8 years (mean±SD) and at the end of the treatment 12±0.8 years. The duration of gonadotropin-releasing hormone analogue treatment was 4.48±0.8 years. At the time of achieving final height, the age of the patients was 18.2±2.0 years and the height was 160.4±7.1 cm. When final height was reached, the authors evaluated bone mineral density Z-score values, levels of bone markers and the function of the hypothalamic-pituitary-gonadal axis. 15 healthy prepubertal girls, 15 pubertal girls and 15 girls who reached final height matched for chronological age were selected as control groups. RESULTS: The majority of the gonadotropin releasing hormone-treated girls reached or almost reached their expected height predicted on the basis of the heights of their parents, but the therapy resulted only in a modest beneficial effect on height gain. Despite the fact that the body weight of patients increased during the treatment, there was no significant difference in their body mass index when they reached their final height as compared to controls. As compared to controls, patients had a decreased bone mineral density at the time when they reached their final height (lumbar spine 2-4 Z score, -0.27±1.2 vs. 0.5±0.7 in controls; p = 0.0377), which could be explained by their overweight that already existed before treatment, lack of exercise and poor calcium uptake. Their menarche occurred 12±4.6 months after discontinuing the treatment. CONCLUSIONS: Gonadotropin releasing hormone analogue therapy exerts a modest beneficial effect on final height gain. There are no detrimental effects on body mass index, bone mineral density and ovarian function after treatment. Side-effects are of minor severity and they are tolerable.

[Dysgenetic male pseudohermaphroditism]. / Dysgeneticus pseudohermaphroditismus masculinus.

The authors report a case of a dysgenetic male pseudohermaphroditism with a 45,X/46,XY karyotype in a mosaic form, which was diagnosed in an infant. The one-week-old infant was evaluated because of proximal hypospadias and retention of the right testis. The results of hormonal tests were the followings: serum FSH 5.2 mU/ml; LH: 2.0 mU/ml; testosterone: 144.3 ng/dl; androstendione: 0.42 µg/l; 17-hydroxyprogesterone: 1.12 ng/ml. Chromosomal analysis revealed 45,X/46,XY karyotype. Fluorescent in vitro hybridization showed that 51% of the lymphocytes had the Y chromosome and the SRY gene. Analysis of the SRY showed no deletion in the AZF a,b,c regions. Pelvic magnetic resonance imaging indicated the presence of vagina between the bladder and the rectum, and it showed a mass measuring 15×8 mm in the right inguinal canal as well as an oval gonadal mass with a size of 13×7 mm in the left scrotum. During surgical intervention, performed at the age of one, the right gonad was removed and biopsy of the scrotal testis was performed. Histological examination revealed dysgenetic testis in both sides. The authors emphasize the necessity of cytogenetic and endocrinological investigations of newborns with perineoscrotal hypospadia and bilateral or unilateral maldescent testes immediately after birth. Surgical removal of the dysgenetic testicular tissue located in the abdominal cavity and its histological evaluation provides separation of mixed gonadal dysgenesis, dysgenetic male pseudohermaphroditism, bilateral gonadal dysgenesis and ovotestis in the 45,X/46,XY mosaic cases. An accurate evaluation is necessary for a correct sex assignment and for surgical intervention to prevent neoplastic degeneration of the dysgenetic gonad.

[Pure 46,XY gonadal dysgenesis]. / 46,XY tiszta gonáddiszgenezis.

The authors report a rare case of pure 46,XY gonadal dysgenesis (Swyer syndrome). Swyer syndrome is associated with 46,XY karyotype, primary amenorrhea as well as the presence of female internal genital tract and bilateral streak gonads in a phenotypic female. The genetic background of this syndrome includes mutations of several genes involved in the testis differentiation cascade. Mutation of the SRY gene accounts for only 10-15% of all 46,XY gonadal dysgenesis cases while the majority cases may be linked to other deficient genes involved in the sex differentiation pathway. The patient was a 16-year-old female who was referred for endocrinological evaluation because of primary amenorrhea. Physical examination revealed a phenotypic female, height 166 cm, weight: 56.5 kg, breast and pubic hair development were Tanner I. and II, respectively. She had female external genitalia. Pelvic magnetic resonance imaging showed a hypoplastic uterus and ovaries at both sides measuring 5×10 mm in size. Chromosomal analysis revealed 46,XY karyotype. Analysis of the SRY and SF1 genes showed no mutations. Serum follicle-stimulating hormone and luteinizing hormone were elevated. Serum tumor marker concentrations were normal. Prophylactic bilateral gonadectomy was performed and histological examination showed bilateral streak gonads. Hormone replacement therapy produced development of secondary sexual characters and 1.5 years after treatment the patient had menarche. Authors conclude that karyotype analysis should be performed in adolescent with primary amenorrhea. After establishment of the diagnosis, dysgenetic gonads should be removed because of the high risk of gonadal neoplasia.

[Mixed gonadal dysgenesis associated with an isodicentric Y chromosome]. / Izodicentrikus Y-kromoszómához társuló kevert gonáddiszgenezis.

Authors report a case of mixed gonadal dysgenesis with a karyotype containing an isodicentric Y chromosome in mosaic form, which was diagnosed in an infant. They emphasize the necessity of the special investigations of newborn with perineoscrotal hypospadia and bilateral or unilateral maldescent testes immediately after birth. The result of accurate evaluation provides correct sex assignment and the prevention of the neoplastic degeneration of a dysgenetic gonad.

[Prevalence of celiac disease in Turner syndrome]. / Coeliakia prevalenciája Turner-szindrómában.

INTRODUCTION AND AIM: Percentage of coeliac disease among patients with Turner syndrome is given differently in a few publication. The aim of the study was to assess prevalence of celiac disease in Turner syndrome. PATIENTS AND METHODS: Serological screening of coeliac disease were performed in 63 patients with Turner syndrome during the last 11.5 years (since 1994). Serological investigations were repeated yearly since 2003 in all patients, and the results of screening of new patients were completed. Theirs first case of coeliac disease was announced in 2004 in Gyermekgyógyászat (Hun). Further positive serological results were found after publication of the first case. RESULTS: Positive results were found in seven of 63 patients (two EmA and five antitransglutaminase IgA positivity). Intestinal biopsy was applied in all 7 cases. Coeliac disease was revealed by histologic analysis in the five cases - 5/63 (7.9%). CONCLUSION: The prevalence of coeliac disease in Turner syndrome seems to be higher than in general population. This can play role in the insufficient effect of growth hormone therapy in the affected patients. The high prevalence indicates that the connection between these disorders can not be coincidental. Their cases and the available data from the publications indicate that screening of coeliac disease in patients with Turner syndrome should be performed and intestinal biopsy is recommended in positive cases.

[Optimizing estrogen treatment in Turner syndrome]. / Törekvéseink az ösztrogénterápia optimalizálására Turner-szindrómában.

INTRODUCTION AND AIM: Authors deducibled from retrospective analysis of patients data with Turner syndrome, who reached near adult height and from results of many multicentre study, that induction of puberty should be designed individually. They show, that estrogen therapy used in their earlier practice for growth promoting did not improve final height of patients. METHODS: The patients were assigned into three groups. The group 1. consisted of untreated patients, who had spontaneous puberty (n = 10). The group 2. consisted of patients, who received oxandrolone and estrogen (n = 18). The group 3. consisted of patients treated with growth hormone (n = 17). In those patients received growth hormone estrogen treatment was started at the age of 14.7 +/- 1.97 years. RESULTS: The final height or near adult height was 144.0 +/- 4.6 cm, 143.5 +/- 1.8 cm, and 154.2 +/- 7.0 cm in group 1, 2 and 3 respectively. The final height was not greater in the group 2. compared to that found in patients who developed spontaneous puberty (group 1.). CONCLUSION: The individual estrogen therapy in patients treated with growth hormone allows feminization, as well as the best adult height, without the occurrence of the more serious mental disturbances.

Mutational analysis of Hungarian patients with androgen insensitivity syndrome.

OBJECTIVE: To support the clinical diagnosis of androgen insensitivity syndrome (AIS), we performed mutational analysis of the androgen receptor gene. DESIGN: Clinical, hormonal and molecular genetic data of ten undervirilized genetic male patients living in Hungary were recorded. METHODS: PCR-based single strand conformation polymorphism (SSCP) analysis was used to study the whole coding region of the androgen receptor gene. Direct fluorescent sequencing was applied when aberrant migration was detected by SSCP. RESULTS: Five different mutations were identified in five unrelated genetic male patients with abnormal sexual differentiation. One of these mutations was novel, while the other four mutations have been described previously in the literature. One of the mutations identified earlier in individuals with sporadic AIS showed a familial inheritance pattern in our study group. No abnormality of the androgen receptor gene was identified in three patients clinically suspected to have partial AIS. CONCLUSION: Application of molecular techniques helped to clarify the diagnosis in patients with disorders of male sexual differentiation.

[Hyperinsulinemia, insulin-like growth factor-I, insulin-like growth factor-binding protein-1, and sex-hormone binding-globulin in prepubertal and pubertal girls with premature adrenarche]. / A hyperinsulinaemia, az inzulinszerú növekedési faktor-I, inzulinszerú növekedési faktort kötó fehérje-1, a nemi hormont kötó globulin vizsgálata a prepubertáskorú és pubertáskorú leányoknál, akiknél praematurus adrenarche lépett fel.

Precocious adrenarche is defined as the development of pubic hair before the age of 8 years in girls and 9 years in boys. Pubarche caused premature adrenarche in girls has been considered as a normal variant of pubertal development for years. Recently, it is cleared that premature pubarche can be considered as a marker of increased risk for endocrine and metabolic abnormalities. Precocious adrenarche in affected girls is associated with hyperinsulinaemia and functional ovarian hyperandrogenism during puberty. Authors investigated serum levels of insulin-like growth factor-I (IGF-I), insulin-like growth factor-binding protein-1 (IGFBP-1), insulin-like growth factor-binding protein-3 (IGFBP-3), sex hormone binding-globulin (SHBG) and levels of insulin during oral glucose tolerance test in 34 girls with premature adrenarche in 38 age- and BMI-matched healthy controls. Affected girls were assigned into prepubertal and pubertal subgroups. It has been shown that hyperinsulinaemia, decrease in IGFBP-1 and increase IGF-I levels may be present in some affected prepubertal patients. In the pubertal group, in addition to hyprinsulinaemia, decreased IGFBP-1 and increased IGF-I levels an attenuated SHBG level was observed. According to the authors, these laboratory parameters may predict endocrine and metabolic abnormalities in later life. The observed correlations support the hypothesis that insulin/IGF system plays role in the pathogenesis of hyperandrogenism in premature adrenarche and in later hormonal and metabolic changes.