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Congenital Adrenal Hyperplasia (congenital + adrenal_hyperplasia)
Selected AbstractsSonography in prenatal diagnosis of congenital adrenal hyperplasiaPRENATAL DIAGNOSIS, Issue 8 2004Julien Saada Abstract Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with an incidence of 1/15 000. More than 90% of CAH cases result from mutations of CYP21, leading to 21-hydroxylase deficiency. In its classical form, CAH is severe and consists of the virilizing (increase of androgens) and salt-wasting (lack of aldosterone) phenotype. When a proband exists, early prenatal diagnosis for CAH can be performed by direct molecular analysis in the first trimester. We describe herein two cases suggesting that the prenatal diagnosis of CAH can be initiated by the sonographic appearance of the adrenal gland at the second-trimester scan in the absence of a family history. Copyright © 2004 John Wiley & Sons, Ltd. [source] Congenital adrenal hyperplasia in adults: a review of medical, surgical and psychological issuesCLINICAL ENDOCRINOLOGY, Issue 1 2006Cara Megan Ogilvie Summary Our knowledge of the experience of adults with congenital adrenal hyperplasia (CAH) as they pass through life is only now emerging. In this review we gather medical, surgical and psychological literature pertaining to adults with CAH and consider this alongside practical experience gained from a dedicated adult CAH clinic. There is increasing awareness for the need for multidisciplinary teams who have knowledge of CAH particularly with respect to gynaecological surgery and clinical psychology for women and testicular function in men. Routine management of CAH comprises adjustment of glucocorticoid and mineralocorticoid treatment according to individual needs balancing biochemical markers, compliance and long term risks. Bone density is one such long term concern and is not greatly reduced in most individuals with CAH. More recently, attention has turned to cardiovascular risk factors and catecholamine deficiency in adults with CAH. Women with CAH require access to an experienced gynaecologist, specialised pregnancy care and psychosexual support. The very low fertility rates for women with CAH previously reported appear to be improving with time. Men with CAH are often lost to follow up and therefore miss out on surveillance for hypogonadism either through the effect of adrenal rests of from suppression of gonadotrophins resulting in a high prevalence of oligospermia. [source] Evaluating the accuracy of Malformations Surveillance Program in detecting virilization due to congenital adrenal hyperplasiaCONGENITAL ANOMALIES, Issue 1 2005Julie Travitz ABSTRACT Malformations surveillance programs of newborn infants have been developed as a method for identifying serious and relatively common birth defects. The virilization of newborn infants with the classic 21-hydroxylase form of congenital adrenal hyperplasia must be identified early if the associated metabolic crisis in the perinatal period is to be prevented. We compared the detection of virilization associated with 21-hydroxylase congenital adrenal hyperplasia in infants by three methods: an ,active' malformations surveillance of medical records at a large urban hospital; routine medical care by examining physicians; and newborn biochemical screening of blood samples. The experience at a large maternity center in Boston, since 1972, showed that pediatricians often recognized affected females (6/6), but not males (0/2); the state newborn screening program, begun in 1990, identified correctly all affected males and females. The Active Malformations Surveillance Program was the least effective screening method, identifying four of six affected females and neither of the affected males. The low rate of detecting affected females by the Surveillance Program was attributed to a failure to sensitize the research assistants to the importance of physicians' notations regarding the signs and symptoms of virilization. The failure of examining physicians, and thereby, the malformations surveillance program, to detect virilized newborn males was due to the lack of consistent associated physical features. These comparisons between these three methods of detection can be used to design and improve malformations surveillance programs. [source] Universal newborn screening and adverse medical outcomes: A historical noteDEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 4 2006Jeffrey P. Brosco Abstract Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and genetic conditions. Although the benefits of such screening programs appear to outweigh their costs, some critics have claimed that historical examples of inadvertent harm ensuing from false-positive screening results and subsequent inappropriate medical treatment should make us wary of expanding universal newborn screening. In this essay, we report the results of a review of the published literature to assess whether the extension of screening from at risk populations to all newborns led to substantial morbidity and mortality from misguided medical treatment. We provide a historical overview of universal newborn screening programs in the United States, and then focus on six early NBS programs: congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine disease. Our comprehensive search of published sources did not reveal a widespread problem of harm ensuing from medical treatment of children with false positive screening test results. © 2006 Wiley-Liss, Inc. MRDD Research Reviews 2006;12:262,269. [source] Fetal programming and fetal psychologyINFANT AND CHILD DEVELOPMENT, Issue 1 2010Peter T. Ellison Abstract The introduction of the ,fetal programming hypothesis', first in epidemiology, subsequently in a broad range of disciplines concerned with developmental biology, has generated new interest in phenotypic plasticity, the mechanisms that govern it, and its place in evolutionary biology. A number of epidemiological studies link small size at birth, assumed to be a consequence of constrained prenatal energy availability, with adverse effects on the risk of chronic diseases later in life. The cluster of chronic diseases associated with the metabolic syndrome and alterations of glucose metabolism are particularly implicated. Recent evidence suggests that epigenetic modification of gene expression affecting the hypothalamic-pituitary-adrenal (HPA) axis may be involved in these effects. In animal studies epigenetic alteration of HPA axis activity and responsiveness is associated with changes in adult behaviour and stress responsiveness. The potential for similar effects to contribute to psychological and psychiatric outcomes in humans has been explored in a number of contexts, including famine exposure, observed covariance with birth weight, and prenatal dexamethasone treatment of fetuses at risk of congenital adrenal hyperplasia. While fetal programming effects have now been widely demonstrated across species and human populations, the adaptive significance of these effects is still a matter of debate. Copyright © 2010 John Wiley & Sons, Ltd. [source] Rapid screening assay of congenital adrenal hyperplasia by measuring 17,-hydroxyprogesterone with high-performance liquid chromatography/electrospray ionization tandem mass spectrometry from dried blood spotsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2002Chien-Chen Lai Abstract A rapid, simple, and specific method was developed for the diagnosis of congenital adrenal hyperplasia (CAH) from dried blood spots on newborn screening cards based on high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). The usefulness of 17,-hydroxyprogesterone (17OH-P) determination on dried filter-paper blood samples from patients with CAH caused by 21-hydroxylase deficiency was evaluated. The LC/MS/MS detection of 17OH-P was rapid, <4 min. The intra- and interday accuracy and precision of the method were <7%. Our procedure maintained good linearities (R2 > 0.992) and recovery rate (>83%). We used this new method to directly determine the 17OH-P levels in dried blood specimens from abnormal children of various ages, with a detection limit of 20 ng/ml (,240 pg), to avoid the time-consuming derivatization steps required by the gas-chromatography/mass spectrometry (GC/MS) method. Four dried filter-paper blood samples of CAH patients (three girls and one boy, 1,14 years old) were all quantified in an LC/MS/MS study and revealed high 17OH-P levels (>90 ng/ml). After treatment, all of the elevated 17OH-P levels either decreased or disappeared. Compared with CAH patients, 17OH-P was nearly undetectable (<20 ng/ml) in the normal infants by LC/MS/MS. This LC/MS/MS assay is not only useful for both diagnosis and monitoring of treatment of CAH in all other age groups, it also can be used as a screening test for CAH infants. In this study, we provided the first data on 17OH-P in dried blood specimens affected with CAH using HPLC/ESI-MS/MS. J. Clin. Lab. Anal. 16:20,25, 2002. © 2002 Wiley-Liss, Inc. [source] Sonography in prenatal diagnosis of congenital adrenal hyperplasiaPRENATAL DIAGNOSIS, Issue 8 2004Julien Saada Abstract Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder with an incidence of 1/15 000. More than 90% of CAH cases result from mutations of CYP21, leading to 21-hydroxylase deficiency. In its classical form, CAH is severe and consists of the virilizing (increase of androgens) and salt-wasting (lack of aldosterone) phenotype. When a proband exists, early prenatal diagnosis for CAH can be performed by direct molecular analysis in the first trimester. We describe herein two cases suggesting that the prenatal diagnosis of CAH can be initiated by the sonographic appearance of the adrenal gland at the second-trimester scan in the absence of a family history. Copyright © 2004 John Wiley & Sons, Ltd. [source] Prenatal diagnosis of 21-hydroxylase deficiency caused by gene conversion and rearrangements: pitfalls and molecular diagnostic solutionsPRENATAL DIAGNOSIS, Issue 13 2002Rong Mao Abstract Objectives The present paper reports the prenatal diagnosis of congenital adrenal hyperplasia (CAH) in two cases of 21-hydroxylase deficiency. DNA diagnostic errors can be caused by the presence of the highly homologous 21-hydroxylase pseudogene, CYP21P, adjacent to the functional gene, CYP21. The present paper details how complex gene conversions and rearrangements between the CYP21 and CYP21P pose unique complications for prenatal diagnosis. Methods Analysis of eight common mutations in the 21-hydroxylase gene as well as deletion of the entire gene is accomplished using polymerase chin reaction (PCR) followed by amplified created restriction site (ACRS) or allele-specific oligohybridization (ASO) and Southern blot followed by hybridization to a CYP21-specific probe. Linkage analysis was performed using microsatellite markers flanking the CYP21 gene. Results The direct mutation detection assay indicated a complicated gene conversion and rearrangement in the probands of both families. Interpretation of these rearrangements made it difficult to determine whether or not the fetuses would be affected with CAH. Linkage studies revealed that each fetus had inherited both parental disease chromosomes and was therefore predicted to be affected with CAH. Conclusion As observed in the two reported cases, direct DNA analysis may provide limited information due to gene conversion or rearrangement between the CYP21 and CYP21P genes. These cases suggest that direct mutation detection should be supported by linkage analysis, whenever possible, to provide more comprehensive information for the family. Copyright © 2002 John Wiley & Sons, Ltd. [source] ORIGINAL RESEARCH,INTERSEX AND GENDER IDENTITY DISORDERS: Gender Assignment and Medical History of Individuals with Different Forms of Intersexuality: Evaluation of Medical Records and the Patients' PerspectiveTHE JOURNAL OF SEXUAL MEDICINE, Issue 4i 2007Lisa Brinkmann PhD ABSTRACT Introduction., Until now, there are only few studies that focus on the specific treatment experiences of people with intersexuality and evaluate their outcome in terms of psychological, physical, and social well-being. Further, the presentation of the patients' perspective is often neglected in research. Aim., Overview of preliminary results of the Hamburg-Intersex-Study on gender assignment and medical history of adult subjects with intersexuality (disorders of sex development), as well as the patients retrospectively stated thoughts and feelings regarding these interventions. Main Outcome Measures., Medical records from participants of the study were analyzed. The subjective attitudes and evaluation of the treatment measures were assessed with a self-constructed questionnaire. Data on psychological well-being were measured with the Brief Symptom Inventory. Methods., In total, 37 adult participants (mean age 30.6 years) with following diagnosis were included: congenital adrenal hyperplasia, complete and partial androgen insensitivity syndrome, gonadal dysgenesis and disturbances of the androgen biosynthesis, such as 5 alpha reductase deficiency and 17 beta hydroxysteroid deficiency. Results., The majority of participants had (often multiple) genital surgery to correct the appearance of their genitalia and/or to enable sexual functioning. The diagnostic groups differ not only in amount and invasiveness of experienced surgical and medical treatment but also in the subjective and retrospective evaluation of the treatment measures and in the amount of reported psychological distress. Conclusion., Many subjects stated to have experienced the medical procedures and care very negatively, whereby the aspects of secrecy, untruthfulness, and concealment were stated as most difficult and burdening. Brinkmann L, Schuetzmann K, and Richter-Appelt H. Gender assignment and medical history of individuals with different forms of intersexuality: Evaluation of medical records and the patients' perspective. J Sex Med 2007;4:964,980. [source] Genital sensation after feminizing genitoplasty for congenital adrenal hyperplasia: a pilot studyBJU INTERNATIONAL, Issue 1 2004N.S. Crouch OBJECTIVE To assess sensation in the clitoris and vagina in women with congenital adrenal hyperplasia (CAH) who have previously had genital surgery, and to evaluate sexual function in this group as the latter, and particularly the experience of orgasm, appear to be closely related to sensitivity. PATIENTS AND METHODS Six women were recruited from a multidisciplinary clinic specialising in intersex conditions, and representing an initial cohort from a larger ongoing study. The patients were asked to complete a postal questionnaire with a specialized sexual function assessment. Thermal, vibratory and light-touch sensory thresholds were assessed in the clitoris and vagina using a genito-sensory analyser and Von Frey filaments. RESULTS All six women had highly abnormal results for sensation in the clitoris. Only three of them had an introitus capable of admitting the vaginal probe, and the vaginal sensory data of all three were within the validated ranges. A self-administered sexual function assessment was completed by the five women who were sexually active. The scores indicated sexual difficulties, particularly in the areas of infrequency of intercourse and anorgasmia. CONCLUSIONS The sensory data for all six women were outside the normal range for the clitoris. The results for the upper vagina, which had not had surgery, were within normal ranges. These findings suggest that genital surgery may disrupt sensory input. Sexual function also appears to be impaired and this may relate to the compromised sensitivity and restricted introitus. The possibility that women with CAH have deficient clitoral sensation ab initio cannot be excluded. These striking findings must be evaluated further in the light of the controversy about the issue of genital surgery in children with CAH. [source] Diversion colitis in children with colovaginoplastyBJU INTERNATIONAL, Issue 9 2001H.A. Syed Objective To highlight the occurrence of diversion colitis and its effects in colovaginoplasty. Patients and methods The records of 18 children who had undergone colovaginoplasty were reviewed retrospectively. Nine patients had androgen-insensitivity syndrome and three each had congenital adrenal hyperplasia, vaginal agenesis and Mayer,Rokitansky syndrome. Through an abdominoperineal approach a segment of sigmoid colon was isolated on its vascular pedicle and brought to the perineum in the plane between the urethra and rectum, as a blind pouch or as an interposition between the proximal vagina and the perineum. The mean (range) follow-up was 5 (1.5,8) years. Results There were no major complications during the early follow-up. Three patients developed severe vaginal discharge with bleeding 2,7 years after colovaginoplasty; examination showed erythema, oedema, ulceration and bleeding. Histology confirmed the classic features of diversion colitis in all three patients. One child responded to vaginal irrigation with a solution of short-chain fatty acids, and the other two were treated with steroid enemas and mesalazine after a poor response to short-chain fatty acids. One of these patients has required surgical reduction of an excessively long neovagina. Conclusion Symptomatic diversion colitis can occur after colovaginoplasty. The severity of the symptoms raises concerns about the use of colovaginoplasty in children and alternative techniques of vaginal replacement should be considered in the first instance. [source] Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiencyACTA PAEDIATRICA, Issue 5 2009Thomas MK Völkl Abstract Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control. Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI. Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 ,g/L) compared to the matched controls (6.7 ,g/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage. Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients. [source] Unfavourable trends in cardiovascular and metabolic risk in paediatric and adult patients with congenital adrenal hyperplasia?CLINICAL ENDOCRINOLOGY, Issue 2 2010Christiaan F. Mooij Summary Context, As a result of the introduction of treatment with glucocorticoids and mineralocorticoids, now 60 years ago, congenital adrenal hyperplasia has become a lifelong chronic disease. Whether long-term treatment of the disease leads to long-term side effects remains unknown. In this respect, especially cardiovascular risk seems to be important. Evidence synthesis, We reviewed the reported prevalence of conventional cardiovascular risk factors, i.e. obesity, insulin resistance, high blood pressure and dyslipidaemia in patients with congenital adrenal hyperplasia. Overall, the studies suggest a tendency towards an increased body mass index and fat mass, the presence of insulin resistance and hypertension, although data are relatively scarce and obtained in heterogeneous populations. Conclusions, Our findings suggest that adult CAH patients tend to have a cluster of metabolic risk factors, which are consistent with the metabolic syndrome. This notion may have consequences for the care for this group of patients. [source] Transient anomalies in genital appearance in some extremely preterm female infants may be the result of foetal programming causing a surge in LH and the over activation of the pituitary,gonadal axisCLINICAL ENDOCRINOLOGY, Issue 5 2008Ronda Greaves Summary Aim, Animal studies have linked foetal programming with the development of the polycystic ovarian syndrome, and metabolic syndrome, in adulthood. The objective is to describe the investigation of four extreme-premature female infants born between 25 and 29 weeks' gestation with apparent genital abnormalities in association with unusually high androgens and gonadotrophins, to postulate a cause and to raise awareness of pitfalls in assessment of these infants. Methods, Clinical examination and biochemical evaluation of four infants referred for apparent congenital ambiguity. Results, Female gender was assigned at birth. Chromosome analysis confirmed 46XX, urine steroid profiles demonstrated no evidence of congenital adrenal hyperplasia and only the expected levels of foetal adrenal steroids. Elevated LH (up to 162 IU/l), testosterone (up to 2·6 nmol/l), ,4 androstenedione (up to > 35 nmol/l) and dehydro-epiandrosterone sulphate (DHEAS) (up to 26·6 µmol/l) were seen in all four infants. These decreased over time but were significantly different from a control population of premature infants of similar gestational age. Conclusions, We postulate that the clinical pattern of apparent clitoral enlargement in some extremely premature infants may reflect true temporary virilization due to an unusually high (or excessive) LH surge, in turn causing high foetal androgens. Foetal programming of gonadotrophin excess is probably the primary cause of androgen increase, in turn causing virilization, in some extreme-premature infants. These may potentially be a group at future risk of polycystic ovary or metabolic syndrome, however, further work needs to be conducted to substantiate this hypothesis. [source] Congenital adrenal hyperplasia in adults: a review of medical, surgical and psychological issuesCLINICAL ENDOCRINOLOGY, Issue 1 2006Cara Megan Ogilvie Summary Our knowledge of the experience of adults with congenital adrenal hyperplasia (CAH) as they pass through life is only now emerging. In this review we gather medical, surgical and psychological literature pertaining to adults with CAH and consider this alongside practical experience gained from a dedicated adult CAH clinic. There is increasing awareness for the need for multidisciplinary teams who have knowledge of CAH particularly with respect to gynaecological surgery and clinical psychology for women and testicular function in men. Routine management of CAH comprises adjustment of glucocorticoid and mineralocorticoid treatment according to individual needs balancing biochemical markers, compliance and long term risks. Bone density is one such long term concern and is not greatly reduced in most individuals with CAH. More recently, attention has turned to cardiovascular risk factors and catecholamine deficiency in adults with CAH. Women with CAH require access to an experienced gynaecologist, specialised pregnancy care and psychosexual support. The very low fertility rates for women with CAH previously reported appear to be improving with time. Men with CAH are often lost to follow up and therefore miss out on surveillance for hypogonadism either through the effect of adrenal rests of from suppression of gonadotrophins resulting in a high prevalence of oligospermia. [source] Neonatal salt-wasting and 11 ,-hydroxylase deficiency in a child carrying a homozygous deletion hybrid CYP11B2 (aldosterone synthase),CYP11B1 (11 ,-hydroxylase)CLINICAL GENETICS, Issue 3 2004B Ezquieta This article reports the case of a boy diagnosed at 1.8 years of age with congenital adrenal hyperplasia due to 11 ,-hydroxylase deficiency. The patient showed salt-wasting episodes during the neonatal period. On molecular analysis, a homozygous deletion hybrid (CYP11B2,CYP11B1) involving the CYP11B locus at 8q24.3 was found. Southern blot analysis showed the break point of the chimera gene to be located before intron 5; sequence analysis identified it at exon 4 between codons 202 and 248. This CYP11B2(5,)/B1(3,) hybrid should lack aldosterone synthase activity (due to the CYP11B1 residues at exons 5 and 6), and the enzyme it codes for should not be promoted by adrenocorticotropic hormone (ACTH) (CYP11B2 promoter sequences). The patient phenotype , neonatal salt-wasting and 11 ,-hydroxylase deficiency , is in agreement with this hybrid structure. This is the first time a homozygous deletion hybrid generated by unequal crossover has been described in exon 4. This genetic lesion appears to be the reciprocal product from the recombination event that causes glucocorticoid-remediable aldosteronism, a duplication dominant allele (CYP11B2,CYP11B1/B2,CYP11B1) coding for additional aldosterone synthase activity regulated by ACTH. The clinical presentation of the condition in this patient contributes to the in vivo understanding of the regulation of this complex locus in which two ,duplicated' genes have evolved different regulatory and enzymatic activities involved in mineralocorticoid and glucocorticoid synthesis in the adrenal glands. The fact that this allele was first predicted and has now been documented clinically and molecularly in vivo is particularly noteworthy. [source] Gene conversion (655G splicing mutation) and the founder effect (Gln318Stop) contribute to the most frequent severe point mutations in congenital adrenal hyperplasia (21-hydroxylase deficiency) in the Spanish populationCLINICAL GENETICS, Issue 2 2002B Ezquieta This study addresses the contributions of gene conversion and a founder effect to the distribution of the two most frequent severe point mutations of the 21-hydroxylase (21OH) gene causing congenital adrenal hyperplasia: the 655G splicing mutation at intron 2, and Gln318Stop in a Spanish population. Direct and indirect analyses of segregated mutant and normal 21OH genes in 200 Spanish families (classic and nonclassic 21OH deficiency) were performed. Both mechanisms were found to contribute to different degrees to the defective investigated alleles. The 655G splicing mutation (62 alleles, 15.5%) seemed to be almost exclusively related to recent conversion events, whereas Gln318Stop (33 alleles, 8.3%) is more likely to be due to the dissemination of remotely generated mutant alleles. Other severe defective alleles, 8 bp-deletion (13 alleles, 3.3%), 306insT (5 alleles, 1.3%), and gene deletions (43 alleles, 11%), as well as the mild mutation Val281Leu (120 alleles, 30%), also appear to be strongly associated with particular D6S273 alleles. Although gene conversion contributes to the generation of severe 21OH alleles, the high frequency of some severe mutations in different geographic areas is consistent with a founder effect. [source] | ||||||||||||||||