Objective: To analyze the mutational spectrum of steroid 21-hydroxylase (CYP21) and the genotypephenotype correlation in patients with congenital adrenal hyperplasia (CAH) registered in the Middle European Society for Pediatric Endocrinology CAH database, and to design a reliable and rational approach for CYP21 mutation detection in Middle European populations. Design and methods: Molecular analysis of the CYP21 gene was performed in 432 CAH patients and 298 family members. Low-resolution genotyping was performed to detect the eight most common point mutations. High-resolution genotyping, including Southern blotting and sequencing was performed to detect CYP21 gene deletions, conversions, point mutations or other sequence changes. Results: CYP21 gene deletion and In2 and Ile172Asn mutation accounted for 72.7% of the affected alleles in the whole study group. A good genotype -phenotype correlation was observed, with the exception of Ile172Asn and Pro30Leu mutations. In 37% of patients low resolution genotyping could not identify the causative mutation or distinguish homozygosity from hemizygosity. Using high-resolution genotyping, the causative mutations could be identified in 341 out of 348 analyzed patients. A novel mutation Gln315Stop was found in one simple virilising CAH (SV-CAH) patient from Austria. In the remaining seven patients polymorphisms were identified as the leading sequence alteration. The presence of elevated basal and ACTH-stimulated 17-hydroxyprogesterone, premature pubarche, advanced bone age and clitoral hypertrophy directly implicated Asn493Ser polymorphism in the manifestation of nonclassical-(NC) and even SV-CAH. Conclusions: By genotyping for the most common point mutations, CYP21 gene deletion/conversion and the 8 bp deletion in exon 3, it should be possible to identify the mutation in 94 -99% of the diseased alleles in any investigated Middle European population. In patients with a mild form of the disease and no detectable mutation CYP21 gene polymorphisms should be considered as a plausible disease-causing mutation.European Journal of Endocrinology 153 99-106

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Despite the fact that congenital adrenal hyperplasia (CAH) is one of the most common inborn endocrine disorders, some patients are not identified, or may even die, in an acute salt-losing crisis. In a retrospective study covering the last 30 yr, we examined the time elapsing before diagnosis of CAH patients, in 5 Middle European countries, and the mortality rate in diagnosed patients and their siblings during childhood; we also attempted to estimate how many patients are not diagnosed clinically each year. Basic and follow-up clinical data and the family histories of 484 patients with classical forms of CAH diagnosed between 1969 and 1998 were collected and recorded in 5 Middle European countries. The sex-ratio, time elapsing before diagnosis, and mortality among siblings and patients were calculated, and the number of undiagnosed patients was estimated. We found significantly fewer genetic males (43.0%) than females (57.0%) among 484 classic CAH patients, and the percentage of diagnosed boys did not increase with time; 64.7% of them suffered from the salt-wasting (SW) form, and 35.3% from the simple virilizing (SV) form, of the disease. The diagnosis of CAH was established significantly later in males than in females in both forms [SW: 26 vs. 13 days (median), P < 0.0001; SV: 5.0 vs. 2.8 yr, P = 0.03]. Infant mortality in the general population was significantly lower than in either siblings (1.8% vs. 7.0%; P < 0.0001) or in SW (2.29% vs. 11.3%; P < 0.0001). According to our calculations, by our current praxis of clinical ascertainment, 2-2.5 SW and up to 5 SV stay undiagnosed, out of 40 expected CAH patients per year in the countries investigated. Both clinical detection and treatment of CAH patients, at least in males, were insufficient in the five Middle European countries examined during the last 30 yr. Neonatal mass screening and/or greater awareness of the medical community are discussed as ways of improving the efficacy of CAH management. Our experience may be applicable to other countries with similar health care systems.

Traumatic brain injury (TBI) is a frequent cause of neuroendocrine dysfunction typically in male adults. Head injuries are also common in childhood, but only a few case reports outlined the endocrine consequences. The aim of this study was to reveal anterior pituitary function in children with history of hospitalization due to mild to severe head trauma. Our endocrine follow-up study was performed between October 2003 and February 2004 in the Pediatric Department of Petz Aladár County Teaching Hospital, Gyor, Hungary. Twenty-six children (17 boys and nine girls, aged 11.47 +/- 0.75 years) at 30.6 +/- 8.3 months after head injury and 21 age-matched controls were enrolled. Basal and stimulated anterior pituitary and peripheral hormone concentrations were measured by routine laboratory methods. Pituitary dysfunction was detected in 61% of patients with TBI history. All growth hormone (GH) parameters measured and calculated were significantly (p < 0.05) lower in TBI group than in controls after L-DOPA stimulation. Similar difference was detected 60 min after insulin provocation. Forty-two percent of all TBI children showed insufficient growth hormone (GH) response in both stimulation tests, 73% of these cases were boys. Cortisol levels of TBI patients were significantly (p < 0.05) lower all through the insulin test than values measured in control group. The degree of pituitary dysfunction was independent from the severity of TBI. Our study confirms the high risk for hypopituitarism in children with TBI despite the lack of obvious clinical symptoms. We suggest screening of pituitary function after any kind of brain trauma requiring hospitalization in childhood.

Background: Longitudinal growth and bone age (BA) development are the most important clinical parameters for monitoring adequate glucocorticoid replacement in children with congenital adrenal hyperplasia (CAH). Aim of the Study: To analyze the growth pattern of patients treated for CAH of the salt wasting (SW) and simple virilizing (SV) clinical forms; to evaluate final height as compared to reference data and individual target height; to evaluate the course of BA development. Patients and Methods: A large database of 598 patients with CAH was created in 5 Central European countries and growth data of 341 treated patients with 21-hydroxylase deficiency were analyzed retrospectively. The patients were of Caucasian origin. Centiles were constructed in a cross-sectional manner and an additional longitudinal analysis was performed in order to evaluate the pubertal growth spurt by applying particular statistical methods (Preece-Baines model). Results: The growth of SW CAH patients was impaired in infancy and early childhood (0–3 years of age), but followed normal patterns in childhood until puberty. In contrast, children with SV CAH had normal patterns of growth in infancy and early childhood and were considerably taller than healthy references during childhood. In the longitudinal study, peak height velocity in both boys and girls was normal, but it occurred at an earlier age than in the standard population. The final height of patients with CAH was reduced in comparison to both the reference and the individual target height. No correlations were found between final height and age at the start of the therapy in SV patients or between final height and year of birth. BA was advanced in both types of CAH, but more accelerated in SV patients. Conclusion: Characteristic growth patterns for treated SV and SW CAH children were identified, with a normal pubertal growth spurt and reduced final height being observed.

This paper invokes the conceptual framework of Bourdieu to analyse the mechanisms, which help to maintain inappropriate authorship practices and the functions these practices may serve. Bourdieu's social theory with its emphasis on mechanisms of domination can be applied to the academic field, too, where competition is omnipresent, control mechanisms of authorship are loose, and the result of performance assessment can be a matter of symbolic life and death for the researchers. This results in a problem of game-theoretic nature, where researchers' behaviour will be determined more by the logic of competition, than by individual character or motives. From this follows that changing this practice requires institutionalized mechanisms, and change cannot be expected from simply appealing to researchers' individual conscience. The article aims at showing that academic capital (administrative power, seniority) is translated into honorary authorship. With little control, undetected honorary authorship gives the appearance of possessing intellectual capital (scientific merit). In this way a dominant position is made to be seen as natural result of intellectual ability or scientific merit, which makes it more acceptable to those in dominated positions. The final conclusion of this paper is that undemocratic authorship decisions and authorship based performance assessment together are a form of symbolic violence.

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The presence of systemic oxidative stress was proven in hypertensive children and adolescents, irrespective of their BMI.