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      Hydrocortisone dosing in children with classic congenital adrenal hyperplasia: results of the German/Austrian registry

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          Treatment of classic congenital adrenal hyperplasia (CAH) is necessary to compensate for glucocorticoid/mineralocorticoid deficiencies and to suppress androgen excess. Hydrocortisone (HC) is preferred in growing children with classic CAH but recommendations regarding dosage/administration are inconsistent. The aim of this study was to evaluate HC dosing in children with CAH in relation to chronological age, sex, and phenotype based on a multicenter CAH registry.


          The CAH registry was initiated in 1997 by the AQUAPE in Germany. On December 31st 2018, data from 1571 patients were included.


          A custom-made electronic health record software is used at the participating centers. Pseudonymized data are transferred for central analysis. Parameters were selected based on current guidelines. Descriptive analyses and linear regression models were implemented with SAS 9.4.


          We identified 1288 patients on exclusive treatment with hydrocortisone three times daily (604 boys; median age 7.2 years; 817 salt-wasting phenotype, 471 simple-virilizing phenotype). The mean (lower-upper quartiles) daily HC dose (mg/m² body surface area) was 19.4 (18.9–19.8) for patients <3 months ( n = 329), 15.0 (14.6–15.3) for age ≥3–12 months ( n = 463), 14.0 (13.7–14.3) for age 1–5.9 years ( n = 745), 14.2 (14.0–14.5) for age 6 years to puberty entry ( n = 669), and 14.9 (14.6–15.2) during puberty to 18 years ( n = 801). Fludrocortisone was administered in 74.1% of patients with a median daily dosage of 88.8 µg.


          Our analyses showed that still a high proportion of children are treated with HC doses higher than recommended. This evaluation provides comprehensive information on nationwide hydrocortisone substitution dosages in children with CAH underlining the benefit of systematic data within a registry to assess daily practice.

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          Most cited references 31

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          Congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

           P C White,  P Speiser (2000)
          More than 90% of cases of congenital adrenal hyperplasia (CAH, the inherited inability to synthesize cortisol) are caused by 21-hydroxylase deficiency. Females with severe, classic 21-hydroxylase deficiency are exposed to excess androgens prenatally and are born with virilized external genitalia. Most patients cannot synthesize sufficient aldosterone to maintain sodium balance and may develop potentially fatal "salt wasting" crises if not treated. The disease is caused by mutations in the CYP21 gene encoding the steroid 21-hydroxylase enzyme. More than 90% of these mutations result from intergenic recombinations between CYP21 and the closely linked CYP21P pseudogene. Approximately 20% are gene deletions due to unequal crossing over during meiosis, whereas the remainder are gene conversions--transfers to CYP21 of deleterious mutations normally present in CYP21P. The degree to which each mutation compromises enzymatic activity is strongly correlated with the clinical severity of the disease in patients carrying it. Prenatal diagnosis by direct mutation detection permits prenatal treatment of affected females to minimize genital virilization. Neonatal screening by hormonal methods identifies affected children before salt wasting crises develop, reducing mortality from this condition. Glucocorticoid and mineralocorticoid replacement are the mainstays of treatment, but more rational dosing and additional therapies are being developed.
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            Modelling covariance structure in the analysis of repeated measures data.

            The term 'repeated measures' refers to data with multiple observations on the same sampling unit. In most cases, the multiple observations are taken over time, but they could be over space. It is usually plausible to assume that observations on the same unit are correlated. Hence, statistical analysis of repeated measures data must address the issue of covariation between measures on the same unit. Until recently, analysis techniques available in computer software only offered the user limited and inadequate choices. One choice was to ignore covariance structure and make invalid assumptions. Another was to avoid the covariance structure issue by analysing transformed data or making adjustments to otherwise inadequate analyses. Ignoring covariance structure may result in erroneous inference, and avoiding it may result in inefficient inference. Recently available mixed model methodology permits the covariance structure to be incorporated into the statistical model. The MIXED procedure of the SAS((R)) System provides a rich selection of covariance structures through the RANDOM and REPEATED statements. Modelling the covariance structure is a major hurdle in the use of PROC MIXED. However, once the covariance structure is modelled, inference about fixed effects proceeds essentially as when using PROC GLM. An example from the pharmaceutical industry is used to illustrate how to choose a covariance structure. The example also illustrates the effects of choice of covariance structure on tests and estimates of fixed effects. In many situations, estimates of linear combinations are invariant with respect to covariance structure, yet standard errors of the estimates may still depend on the covariance structure. Copyright 2000 John Wiley & Sons, Ltd.
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              Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society* Clinical Practice Guideline


                Author and article information

                Endocr Connect
                Endocr Connect
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                28 April 2021
                01 May 2021
                : 10
                : 5
                : 561-569
                [1 ]Department of Paediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne, Germany
                [2 ]Department of Paediatrics , University Children’s Hospital Dresden, Dresden, Germany
                [3 ]University Children’s Hospital Bochum , Bochum, Nordrhein-Westfalen, Germany
                [4 ]University Children’s Hospital Heidelberg , Heidelberg, Germany
                [5 ]University Children’s Hospital Homburg , Homburg, Germany
                [6 ]University Children’s Hospital Innsbruck , Innsbruck, Austria
                [7 ]Department of Pediatric , Medical University of Vienna, Vienna, Austria
                [8 ]St.Anna Kinderspital , Medical University of Vienna, Vienna, Austria
                [9 ]Department of Biometrics , Otto von Guericke Universität Magdeburg, Magdeburg, Sachsen-Anhalt, Germany
                [10 ]University Children’s Hospital Erlangen , Erlangen, Germany
                [11 ]Institute of Epidemiology and Medical Biometry , ZIBMT, University of Ulm, Ulm, Germany
                Author notes
                Correspondence should be addressed to H Hoyer-Kuhn: heike-katharina.hoyer-kuhn@ 123456uk-koeln.de
                © The authors

                cyp21a2, glucocorticoids, fludrocortisone, treatment


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