Effects of a novel mobile health intervention compared to a multi-component behaviour changing program on body mass index, physical capacities and stress parameters in adolescents with obesity: a randomized controlled trial.

BACKGROUND: Less than 2% of overweight children and adolescents in Switzerland can participate in multi-component behaviour changing interventions (BCI), due to costs and lack of time. Stress often hinders positive health outcomes in youth with obesity. Digital health interventions, with fewer on-site visits, promise health care access in remote regions; however, evidence for their effectiveness is scarce. METHODS: This randomized controlled not blinded trial (1:1) was conducted in a childhood obesity center in Switzerland. Forty-one youth aged 10-18 years with body mass index (BMI) > P.90 with risk factors or co-morbidities or BMI > P.97 were recruited. During 5.5 months, the PathMate2 group (PM) received daily conversational agent counselling via mobile app, combined with standardized counselling (4 on-site visits). Controls (CON) participated in a BCI (7 on-site visits). We compared the outcomes of both groups after 5.5 (T1) and 12 (T2) months. Primary outcome was reduction in BMI-SDS (BMI standard deviation score: BMI adjusted for age and sex). Secondary outcomes were changes in body fat and muscle mass (bioelectrical impedance analysis), waist-to-height ratio, physical capacities (modified Dordel-Koch-Test), blood pressure and pulse. Additionally, we hypothesized that less stressed children would lose more weight. Thus, children performed biofeedback relaxation exercises while stress parameters (plasma cortisol, stress questionnaires) were evaluated. RESULTS: At intervention start median BMI-SDS of all patients (18 PM, 13 CON) was 2.61 (obesity > + 2SD). BMI-SDS decreased significantly in CON at T1, but not at T2, and did not decrease in PM during the study. Muscle mass, strength and agility improved significantly in both groups at T2; only PM reduced significantly their body fat at T1 and T2. Average daily PM app usage rate was 71.5%. Cortisol serum levels decreased significantly after biofeedback but with no association between stress parameters and BMI-SDS. No side effects were observed. CONCLUSIONS: Equally to BCI, PathMate2 intervention resulted in significant and lasting improvements of physical capacities and body composition, but not in sustained BMI-SDS decrease. This youth-appealing mobile health intervention provides an interesting approach for youth with obesity who have limited access to health care. Biofeedback reduces acute stress and could be an innovative adjunct to usual care.

Comorbidities in overweight children and adolescents: do we treat them effectively?

OBJECTIVE: The aim was to analyze the effectiveness of treatment concerning obesity-associated comorbidities in clinical practice. METHODS: A total of 11,681 overweight children with ≥ 6-month follow-up treated at 175 centers specialized in pediatric obesity care in Central Europe were included in this analysis (mean body mass index (BMI) 29.0 ± 5.6 kg m(-)(2), standard deviation score body mass index (SDS-BMI) 2.48 ± 0.54, 45% boys, age 11.4 ± 2.8 years). The changes of weight status, blood pressure, fasting lipids and glucose, and oral glucose tolerance tests were documented by standardized prospective quality documentation software (APV). RESULTS: After follow-up of in median 1.2 (interquartile range 0.9-2.2) years, a mean reduction of -0.15 SDS-BMI was achieved. The prevalence of prehypertension (37->33%) and hypertension (17->12%) decreased, while prevalences of triglycerides >150 mg dl(-1) (22->21%), low-density-lipoprotein-cholesterol >130 mg dl(-1) (15->14%), impaired fasting glucose (6->6%) and impaired glucose tolerance (9->8%) remained stable. Drug treatment according to cutoffs recommended in European obesity guidelines were not frequently indicated (hypertension: 10%; dyslipidemia: 1%, type 2 diabetes <1%). None of the children with dyslipidemia received lipid-lowering drugs and only 1.4% of the children with hypertension were treated with antihypertensive drugs. CONCLUSIONS: Achieving sufficient weight loss to improve obesity associated comorbidities was difficult in clinical practice. Drug treatment of hypertension, dyslipidemia and type 2 diabetes was rarely performed even if it was indicated only in a minority of the overweight children. Future analyses should identify reasons for this insufficient drug treatment of comorbidities and analyze whether the benchmarking processes of APV improve medical care of childhood obesity.

Obese boys at increased risk for nonalcoholic liver disease: evaluation of 16,390 overweight or obese children and adolescents.

OBJECTIVE: Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of population-specific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort. METHODS: In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16,390 children and adolescents (age 12.4±2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) >90th percentile) and obese (>97th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >50 U l(-1)). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis. RESULTS: In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (>99.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; P<0.001), in Xob (obese vs Xob; 9.5:17.0%; P<0.001) and in older age (< 12 vs ≥12 years; 8:12%; P<0.001; adjusted for BMI). ALT >50 U l(-1) was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight=3.2; boys vs girls OR=2.3). CONCLUSION: In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care.

Do centimetres matter? Self-reported versus estimated height measurements in parents.

AIM: An impressive discrepancy between reported and measured parental height is often observed. The aims of this study were: (a) to assess whether there is a significant difference between the reported and measured parental height; (b) to focus on the reported and, thereafter, measured height of the partner; (c) to analyse its impact on the calculated target height range. METHODS/RESULTS: A total of 1542 individual parents were enrolled. The parents were subdivided into three groups: normal height (3-97th Centile), short (<3%) and tall (>97%) stature. Overall, compared with men, women were far better in estimating their own height (p < 0.001). Where both partners were of normal, short or tall stature, the estimated heights of their partner were quite accurate. Women of normal stature underestimated the short partner and overestimated the tall partner, whereas male partners of normal stature overestimated both their short as well as tall partners. Women of tall stature estimated the heights of their short partners correctly, whereas heights of normal statured men were underestimated. On the other hand, tall men overestimated the heights of their female partners who are of normal and short stature. Furthermore, women of short stature estimated the partners of normal stature adequately, and the heights of their tall partners were overestimated. Interestingly, the short men significantly underestimated the normal, but overestimated tall female partners. CONCLUSION: Only measured heights should be used to perform accurate evaluations of height, particularly when diagnostic tests or treatment interventions are contemplated. For clinical trails, we suggest that only quality measured parental heights are acceptable, as the errors incurred in estimates may enhance/conceal true treatment effects.

[How to treat childhood obesity? Importance of primary prevention]. / Comment traiter l'obésité de l'enfant? Importance de la prévention primaire.

The prevalence of childhood obesity increases dramatically. First signs of cardiovascular diseases and type 2 diabetes appear early in life. The treatment of childhood obesity aims at weight maintenance during growth, normalization of body mass index at long-term and prevention of complications. The family based behavioural therapy is a promising approach. It provides simultaneous treatment for the overweight parent and child in order to modify the family environment, to provide role models and support for child behaviour changes. However, this requires group leaders and multiple counselors to meet with families. The treatment should be initiated as soon as possible, as its efficacy is reduced after the onset of puberty. Early preventive interventions that aim to modify both individual's behaviours and the environment are needed.

How a patient homozygous for a 30-kb deletion of the C4-CYP 21 genomic region can have a nonclassic form of 21-hydroxylase deficiency.

A case of nonclassic (NC) 21-hydroxylase deficiency, with a moderately elevated 17-hydroxyprogesterone level (145 nmol/L in filter paper blood spot), was detected in newborn screening. The newborn's phenotype was female, with no sign of virilization. Confirmatory diagnosis revealed elevated serum levels of 17-hydroxyprogesterone and of 21-desoxycortisol, whereas cortisol, PRA, and electrolytes were normal. Hydrocortisone substitution was considered at the age of 6 months, when virilization became obvious. For clinical reasons, this case had to be classified as late-onset congenital adrenal hyperplasia (CAH) with unusually early manifestation. However, the diagnosis of classic 21-hydroxylase deficiency was obtained by Southern blotting studies, showing that she was homozygous for the 30-kb deletion, including the 3' end of CYP21P pseudogene, the C4B gene, and the 5' end of the functional CYP21 gene. Further studies, using PCR and sequencing, were conducted to explain the discrepancy between this genotype, usually associated with a classic salt-wasting form, and the girl's phenotype. Typically, patients homozygous for the 30-kb deletion encoding classic CAH possess a unique CYP21P/21 hybrid gene with the junction site located after the third exon, yielding a nonfunctional pseudogene. The girl in question, however, was heterozygous for the 8-bp deletion, suggesting that the chimeric pseudogene on one allele had a junction site before the third exon. She was compound heterozygous for a 30-kb deletion encoding classic CAH on the paternal allele, and a 30-kb deletion encoding NC CAH on the maternal allele. This novel maternal CYP21P/21 hybrid gene is characterized by a junction site before intron 2 and differs from the normal CYP21 gene only by the P30L mutation in exon 1 and the promoter region of the CYP21P pseudogene. Because the P30L mutation has been described to result in an enzyme with 30-60% activity of the normal P450c21 enzyme, and the CYP21P promoter reduced the transcription to 20% of normal, this puzzling phenotype of a NC CAH with early onset may be fully explained by the genotype of the patient and considered as an intermediate form between the simple virilizing and NC form.

Insulin-like growth factors enhance steroidogenic enzyme and corticotropin receptor messenger ribonucleic acid levels and corticotropin steroidogenic responsiveness in cultured human adrenocortical cells.

In several species, including the human fetus, insulin-like growth factors (IGF-I and IGF-II) have been reported to modulate adrenal steroidogenesis, thus contributing to adrenal cortical differentiation. In the present study, we examined the long term effects of IGF-I and -II on human adult adrenal fasciculata-reticularis cells cultured in a chemically defined medium and compared them to the effects of insulin, human GH, and ACTH. Treatment for 3 days with IGF-I or -II at nanomolar concentrations or with insulin at micromolar concentrations slightly increased the production of androstenedione, cortisol, and dehydroepiandrosterone about 1.5-fold over that by control cells. Moreover, the acute steroidogenic response to ACTH of cells pretreated with IGF-I, IGF-II, or insulin was 3- to 6-fold higher than that of control cells. For each hormone, these effects of IGF-I and -II were dose dependent between 0.1-26 nmol/L (1-200 ng/mL). The secretion of androstenedione was more potently stimulated than that of dehydroepiandrosterone and cortisol, and this effect was more clearly yielded by pretreatment with IGF-II than with IGF-I or insulin. Human GH had no effect on these cells. In cells treated with IGF-I or -II, the messenger ribonucleic acid (mRNA) levels of cytochrome P450 17 alpha-hydroxylase and of 3 beta-hydroxysteroid dehydrogenase were increased, and the abundance of ACTH receptor mRNA was also slightly enhanced, but the mRNA of cytochrome P450 cholesterol side-chain cleavage enzyme was unchanged. In conclusion, IGFs enhance the steroidogenesis and ACTH responsiveness of human adrenocortical cells in culture. We speculate, that by this mechanism, IGFs may contribute to clinical states with hyperandrogenemia.

Is there a local IGF-system in human adrenocortical cells?

There is increasing evidence that in the fetal and postnatal development of the adrenal gland, trophic and differentiating effects of ACTH are locally modulated by a species-specific pattern of growth factors. As we have shown previously in human adult adrenocortical cells (HAC) in culture, IGF-I and, even more, IGF-II enhance the steroidogenesis and ACTH responsiveness. We now examined the secretion of IGFs and their binding proteins (IGFBP) in the medium of 12 serum free primary cultures of HAC by specific RIAs and [125I]IGF ligand blot or by immunoblot, and their long-term regulation by ACTH. HAC secrete 0.41 and 0.91 ng IGF-I and IGF-II/5 x 10(5) cells per day, respectively, and their secretion is significantly stimulated 2- and 1.6-fold, respectively, by ACTH. HAC secrete at least three IGFBPs. The 43-46 kDa and the 29 kDa proteins correspond to glycosylated and fragmented forms of IGFBP-3, and the 36 kDa protein to IGFBP-2. The most abundant protein is the 24 kDa IGFBP, with identical electrophoretic mobility to IGFBP-4. IGFBP-3, as measured by RIA, is in the range of 1 ng/day. None of the IGFBPs is significantly changed by ACTH. Thus, we have evidence for a local IGF system, and the IGF-levels are in a range compatible with a physiological auto or paracrine action on steroidogenesis.

Early manifestations of Prader-Willi syndrome: influence of growth hormone.

Pediatricians and neonatologists now understand the clinical picture of Prader-Willi syndrome (PWS) in infants as genetic tools are available to confirm this diagnosis. Hence, an increasing number of very young, still underweight children are being diagnosed with PWS. Some features, such as low prenatal weight and below-average height, subsequent poor growth velocity and increased body fat, possibly in infancy, may be interpreted as a consequence of early growth hormone (GH) deficiency. This raises the question of when is the best time for the initiation of GH treatment. This article presents the results of a study in which ten very young children with PWS (mean age 1.0 year) were treated with exogenous GH. We conclude that GH treatment in young, underweight children, as well as in older children with PWS: (1) normalizes growth and body proportions; (2) probably reduces fat mass and increases muscle mass; (3) may enhance motor development; and (4) is necessary, but obviously not sufficient, to normalize body composition and fat distribution. Whether there is a benefit in treating children with PWS from such an early age requires longer-term studies.

The use of L-T4 as liquid solution improves the practicability and individualized dosage in newborns and infants with congenital hypothyroidism.

UNLABELLED: Dosage recommendations for the initial therapy of congenital hypothyroidism (CH) in newborns vary between 8 microg/kg/d and 10-15 microg/kg/d. AIM: To evaluate the practicability of LT4 in liquid form and to define the initial dosage for optimal treatment. METHODS: Liquid LT4 solution was administered to 28 consecutive newborns with primary CH. We measured TSH, T3, T4, free T3 and free T4 before therapy and during follow-up up to 2 years. After 2 years a standardized developmental test (Griffith) was performed. RESULTS: The median dosage at start of therapy was 12.3 microg LT4/kg/d and decreased to about 5 microg LT4/kg/d after 9 months. The median time of normalization of TSH (< or =6 mU/l) was 2 weeks. In 21 patients, who received a median starting dosage of 12.7 microg LT4/kg (range 9.8-17.1 microg/kg), TSH levels normalized within a median of 1 week. Seven patients receiving only 10.1 microg LT4/kg normalized their TSH only after a median of 2 months. CONCLUSIONS: Newborns with CH should normalize their TSH within 1-2 weeks. The initial dose necessary to normalize TSH is not lower when a liquid solution is used. The higher dose used in tablets is not due to inefficient absorption, but rather reflects the increased demand for thyroid hormone in the first weeks of life.

Clinical, genetic and functional characteristics of three novel CYP17A1 mutations causing combined 17alpha-hydroxylase/17,20-lyase deficiency.

BACKGROUND: P450c17 has two distinct activities: 17alpha-hydroxylase activity and 17,20-lyase activity. Combined 17alpha-hydroxylase/17,20-lyase deficiency leads to a severe defect in the production of cortisol and sex steroids. In affected males this results in impaired masculinization with ambiguous or female external genitalia. Female patients have normal genitalia but show a lack of pubertal development in adolescence. An increased production of mineralocorticoids often leads to hypertension and hypokalemia in both sexes. METHODS: To better understand the mechanisms of P450c17 deficiency, we studied 2 patients (both 46,XY) with combined 17alpha-hydroxylase/17,20-lyase deficiency of different severity: one with complete lack of masculinization and one with ambiguous genitalia. RESULTS: Four mutations were identified by sequencing of the CYP17A1 gene: I332T and A355T in the less severely affected patient; G111S and R440H in the patient with complete lack of masculinization. The three novel mutations were expressed in COS1 cells and all mutant proteins except I332T showed a complete loss of both enzymatic activities. I332T retained some residual 17alpha-hydroxylase as well as 17,20-lyase activity. CONCLUSION: We identified 2 patients with the phenotypical spectrum of P450c17 deficiency. Three novel mutations in the CYP17A1 gene were identified and their functional characterization provided a good phenotype-genotype correlation. The location of the mutated residues in the three-dimensional model of P450c17 gave some additional insights into its structure-function relationship.

Growth hormone normalises height, prediction of final height and hand length in children with Prader-Willi syndrome after 4 years of therapy.

BACKGROUND: Based on the reported favourable effects of growth hormone (GH) treatment on growth and body composition in Prader-Labhart-Willi syndrome, we studied age dependency and the long-term effects on growth dynamics to elucidate the assumed hypothalamic GH deficiency. METHODS: We examined 23 children treated with hGH (24 U/m(2)/week) during a median of 4 (range 1.5-5.5) years; group 1: 10 young underweight (age 0.3-4.1 years), group 2: 8 prepubertal overweight (age 3.7-9.5 years) and group 3: 5 pubertal overweight children (age 9.0-14.6 years). RESULTS: After 4 years of therapy, height gain amounted to 1.8 SD; height (0.0 SD) and hand length (-0.2 SD) were normalised in the 2 prepubertal groups; in children above 6 years, height prediction approached parental target height. Weight for height rose in group 1 (to 0.64 SD) and decreased in group 2 (to 0.71 SD) to normal levels. Bone maturation of the pubertal children was too advanced to show a clear growth response to GH (height gain 0.42 SD). Even in this group, weight for height was reduced, but remained supernormal. CONCLUSION: Under exogenous GH, growth and body proportions are normalised in prepubertal children. With early institution of treatment, final height prediction reaches the parental target height range after 3 years. Such a growth-promoting effect of exogenous GH has so far only been described in children with GH deficiency.

Intra-adrenal regulation of androgen synthesis.

The adrenal cortex encloses the neuroendocrine medulla and is itself subdivided into three distinct zones, each having a specific function and regulation. While the glomerulosa and the fasciculata control vital systems of mineral and energy supply, which are stringently regulated by higher control factors, the function of the reticularis is less clear, beyond supplying a pool of weak androgens, and consequently we do not understand its redundant regulation. The following questions need to be answered: 1. How is the formation of dehydroepiandrosterone (DHEA) and androstenedione differently regulated from glucocorticoid synthesis in normally functioning adrenals? 2. How might growth factors, which increase prepubertally, prime the adrenarche? 3. The regulation of the 17/20-lyase enzyme activity is one of the key factors of adrenal androgen secretion (review [2]). How can the two activities of the P450c17 enzyme be differently regulated in the same cell in a developmentally dependent fashion? This review focuses on the intra-adrenal growth factor system and on the role of 17/20-lyase regulation, as well as on their possible interactions. The increase of activity of the 17/20-lyase enzymatic activity is necessary for the rise of C19 steroids, while the relative increase of formation of DHEA is only possible in the presence of a low 3beta-hydroxysteroid-dehydrogenase (3betaHSD) activity.

Is there growth hormone deficiency in prader-willi Syndrome? Six arguments to support the presence of hypothalamic growth hormone deficiency in Prader-Willi syndrome.

Prader-Labhart-Willi syndrome (PWS) is the most frequent form of syndromal obesity. Its main features are associated with hypothalamic dysfunction, which has not yet been comprehensively described. The aim of this review is to present arguments to define the presence of genuine growth hormone (GH) deficiency (GHD) in these patients. Decreasing growth velocity despite the onset of obesity, reduced lean body mass in the presence of adiposity, small hands and feet, relatively low insulin-like growth factor-I and low insulin levels, as well as the dramatic effect of GH treatment on growth, support the presence of hypothalamic GHD in PWS. Even though it might be difficult to ultimately prove GHD in PWS because of the obesity-induced counterregulation, the hormonal situation differs from that in simple obesity. The effects of long-term therapies with GH on body composition in these patients are summarized. GH therapy dramatically changes the phenotype of PWS in childhood: height and weight become normal and there is a sustained impact on the net loss of body fat. We conclude that GHD may account for several features of PWS.

Thyroid function and obesity in children and adolescents.

The aim of this retrospective study was to investigate the frequency of thyroid dysfunction as assessed by TSH, T3 and T4 in a large cohort of 290 obese and 280 healthy children. In addition, thyroid autoantibodies were measured in random subgroups of 123 obese and 80 control children, iodine excretion in 50 and thyroid volume in 23 of the obese children. Elevated TSH levels (>4 U/l) were found in 22 obese children (7.5%), but only in one control (0.3%). The medians of TSH and T3 concentrations were normal, but significantly higher in the obese group than in the controls, while T4 levels did not differ. The prevalence of positive thyroid autoantibodies was increased in the obese children, for the most part in those with elevated TSH. There was no evidence for iodine deficiency as a cause of the average increase of TSH. We conclude that in childhood obesity TSH and T3 levels are significantly increased; in most cases, however, these increases are not accounted for by thyroid autoimmunity or iodine deficiency. As a consequence, TSH elevations with normal thyroid hormone levels in obese children don't need any thyroxine treatment, if thyroid disorders were definitely excluded beforehand.

Iodine in contrast agents and skin disinfectants is the major cause for hypothyroidism in premature infants during intensive care.

In 51 sick newborns the influence of two different nonionic, iodine-containing contrast agents, Amipaque (group 1) and Omnipaque (group 2) and of long-term treatment with polyvinylpyrrolidone-iodine (PVP-I) (group 3) on thyroid function was studied. In the dose given, freshly dissolved Amipaque releases roughly 100 micrograms 'free' iodide/kg body weight; this release may be even higher in the solubilized agent Omnipaque because of increased breakdown. Urinary iodine excretion was elevated in all groups on day 5 after iodine exposure. In group 1, which included 17 term newborns, the median TSH level was normal after 5 days and 2 weeks, only 1 case of transient hypothyrotropinemia was observed; T4 and T3 median levels were in the lower range of normal. In groups 2 and 3, which included 8 preterm infants of 15 newborns and 9 preterm infants of 19 newborns, respectively, the median TSH values were elevated and T4 and T3 levels were very low. Hypothyroidism was diagnosed in 6 of the 8 preterm and in 1 of the 7 term newborns of group 2. In group 3, 7 of the 9 preterm and 3 of the 10 term newborns reacted with hypothyroidism. Eight preterm and 3 term newborns had to be substituted with thyroxine. The thyroid function of term newborns was less affected by Amipaque or Omnipaque than by PVP-I. The data show that preterm infants are very sensitive to an iodine load.

Aldosterone metabolism in rat renal tissue in vitro. Formation of lipid soluble metabolites.

In the present study the formation of lipid soluble metabolites from 3H-aldosterone was investigated in vitro in isolated kidneys and kidney and liver slices of Sprague Dawley rats. The steroids were separated by HPLC (forward and reversed phase systems) and detected on-line as UV- or 3H-chromatograms. Apart from an unenzymatically formed substance, isoaldosterone, three less polar metabolites were traced (A1, A2, A3). The structure of the quantitatively most important metabolite (A1), was identified as 5 alpha-dihydroaldosterone using a combination of techniques such as chromatographic comparison with reference steroids, antibody binding and mass spectrometry. Evidence for further conversion of DHaldo to 3 alpha, 5 alpha-tetrahydroaldosterone was obtained in chromatographic and antibody binding studies. The formation of metabolites was not dependent on glomerular filtration. Furthermore it displayed regional heterogeneity with highest activity in the outer medulla. Finally it was observed that the in vitro metabolism of aldosterone was not saturable over a range of initial aldo concentration of 10(-9) to 10(-5) M.

[Adrenal cortex function in children with bronchial asthma in fluticasone therapy]. / Nebennierenrindenfunktion bei Kindern mit Asthma bronchiale unter Therapie mit Fluticason.

In order to study the adverse reaction of a new, inhaled steroid (Fluticasone) on the pituitary-adrenocortical axis in asthmatic children, we investigated 7 children (aged 7 to 15 years) before and during treatment with Fluticason (100-200 micrograms/day). For the dosage tested, we found no depression of adrenal function, neither in circadian cortisol secretion nor in hCRH-stimulation-test. Another 7 asthmatic children under treatment with Budesonide (800 micrograms/day) were examined by the same tests. They equally did not show an adrenocortical suppression. However, in 4 other children under therapy with oral prednisone (2.5 to 7.5 mg/day), there was a marked suppression on adrenocortical function, even with low doses of the steroid. We conclude that Fluticasone (as well as Budesonide) in the above dosages represent a safe therapy for bronchial asthma in children.

Ring Y chromosome: cytogenetic and molecular characterization.

A female patient with Turner syndrome and the karyotype mos45,X/46,X,r(Y)/46,XY is described. Physical mapping of the ring chromosome by Y-specific single-copy and moderately repeated DNA sequences as molecular probes showed that, in addition to the heterochromatic part of Yq, a considerable portion of the Yp has also been lost in the course of the rearrangement. Thus, molecular findings provide independent support that this structurally abnormal sex chromosome is a ring Y and agree with the generally accepted model of ring formation requiring breaks in both chromosome arms. Clinical consequences of Y chromosome mosaicism in patients with Turner syndrome are discussed.

Nonclassical adrenal hyperplasia due to 21-hydroxylase-deficiency: does genotyping predict the clinical manifestation?

8 patients of 7 families with nonclassical adrenal hyperplasia (NCAH) were analysed for defects of the 21-hydroxylase-B-gene. As the defects were small or rare, complete molecular genetic diagnostic up to sequencing of this gene was necessary to detect the genotype, which then was associated with the phenotype. However, mutations in 4 alleles from 3 families are still undetectable. Thus, correct prenatal diagnosis in NCAH-families without index patient remains difficult.