198 results on '"S. Faisal Ahmed"'
Search Results
152. Sex Assignment in Disorders of Sex Development
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Angela K Lucas-Herald and S Faisal Ahmed
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Delayed puberty ,Ambiguous genitalia ,Sex Chromosome DSD ,Sex assignment ,medicine ,Disorders of sex development ,medicine.symptom ,Multidisciplinary team ,Psychology ,medicine.disease ,Psychosocial ,Developmental psychology - Abstract
Disorders of sex development (DSD) are relatively rare conditions with diverse pathophysiology, which usually present in the newborn or adolescent periods. These conditions are very heterogeneous and can present in a variety of different ways, most commonly with ambiguous genitalia noticed in the newborn period or delayed puberty in adolescents. The impact of these disorders on the lives of these patients and their families should not be underestimated. These clinical situations can often be difficult to manage, particularly in those cases where the sex of rearing is uncertain. The needs of each individual patient presenting with DSD conditions must be fully considered, along with the needs of their families and where appropriate, cultural practices. The multidisciplinary team should be involved from early in the diagnosis and ethical principles must be considered at all stages of management of the condition. Key Concepts: Disorders of sex development usually present in the newborn or adolescent periods. There are three broad groups of DSD: sex chromosome DSD; 46,XY DSD and 46,XX DSD. Where there is uncertainty about the sex of a patient, sex assignment should be delayed until appropriate investigations have been carried out. A multidisciplinary team should be involved from an early stage. The psychosocial implications of a diagnosis of DSD must be considered for the family and the patient. Keywords: ambiguous genitalia; gender; multidisciplinary team; sex development; ethics
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- 2012
153. Disorders of sex development: challenges for the future
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Kyriakie Sarafoglou and S Faisal Ahmed
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Male ,medicine.medical_specialty ,46, XX Disorders of Sex Development ,Pediatric endocrinology ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,030209 endocrinology & metabolism ,Primary Ovarian Insufficiency ,Bioinformatics ,Steroidogenic Factor 1 ,Biochemistry ,Variable Expression ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Complete androgen insensitivity syndrome ,030225 pediatrics ,Internal medicine ,medicine ,Humans ,Point Mutation ,Congenital adrenal hyperplasia ,Disorders of sex development ,Allele ,Gynecology ,Disorder of Sex Development, 46,XY ,business.industry ,Biochemistry (medical) ,medicine.disease ,3. Good health ,Mutation (genetic algorithm) ,Female ,business ,Comparative genomic hybridization - Abstract
The perpetual challenge in the diagnosis and management of patients with disorders of sex development (DSD), to paraphrase the adage, is that as our circle of knowledge in the genetic mechanisms of DSD expands, so does the circumference of darkness surrounding it. New technologies (comparative genomic hybridization, sequencing by hybridization, and next generation sequencing) are rapidly generating massive amounts of information on the pathogenesis of DSD (1). The caveat is that identifying a pathogenic mutation may not predict the clinical picture because phenotype can be highly variable, even within the same family (2). Oligogenic modulators, developmental switches, epigenetic influences, environmental stimuli, and even imbalanced cis-regulation of mutant vs. wild-type alleles when mutations are present in a heterozygous state may also be contributing factors to the variable expression of phenotype (3). A major step forward in organizing the molecular and clinical information was the recent change in nomenclature and classification of DSD. In 2006, the Pediatric Endocrine Society (formerly known as the Lawson and Wilkins Pediatric Endocrine Society) and the European Society for Pediatric Endocrinology consensus group defined DSD as congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical, and broadly classified DSD into three groups based upon cytogenetic, hormonal, gonadal histology, and clinical findings: 46,XY DSD, 46,XX DSD, and sex chromosome DSD (4). The classification reflected the natural history of the diagnostic process in which the sex chromosomes are the usual starting point for investigations of a child with atypical genitalia. As our genetic and endocrine understanding of unclassified or syndromic conditions improves, the DSD classification, which continues to gain wide acceptance across the globe (5), has the flexibility to incorporate them into its current structure. But there is still a long way to go to where the genetic information can be used to predict long-term outcomes to provide personalized care for the DSD patient. In some DSD, clinical diagnosis can be confirmed by hormonal and molecular testing. For example, in complete androgen insensitivity syndrome there is an 80 – 90% chance that a 46,XY infant with normal female genitalia and normal testosterone synthesis will have a mutation in androgen receptor gene (6). Similarly, the majority of 46,XX presenting with virilized genitalia will have congenital adrenal hyperplasia with a mutation in CYP21A2 where genotype-phenotype correlations are excellent (7). In cases of XY DSD with partially virilized genitalia, a molecular diagnosis has been relatively elusive so that diagnosis is guided by a thorough clinical, biochemical, and anatomical evaluation of the affected infant. For instance, only about 20% of these cases associated with normal androgen synthesis will have a mutation in the androgen receptor gene (6). Discordance between molecular changes and functional in vitro transactivation studies complicate even further the efforts for attributing the particular DSD phenotype to the identified gene change. Furthermore, such functional studies continue to remain in the realms of research laboratories, and their large-scale clinical utility remains unclear. The recent identification of mutations associated with DSD in a poorly characterized MAPK sig
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- 2012
154. Urinary gonadotrophins: a useful non-invasive marker of activation of the hypothalamic pituitary-gonadal axis
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Jane D McNeilly, S Faisal Ahmed, Sheila Khanna, Peter J Galloway, and Avril Mason
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LH ,medicine.medical_specialty ,Creatinine ,lcsh:RC648-665 ,business.industry ,Maternal and child health ,Research ,Urinary system ,Non invasive ,Puberty ,lcsh:RJ1-570 ,Hypothalamic–pituitary–gonadal axis ,lcsh:Pediatrics ,Urine ,Assessment ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Adolescence ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,FSH ,Medicine ,business ,Normal range - Abstract
Background Non-invasive screening investigations are rarely used for assessing the activation and progression of the hypothalamic-pituitary gonadal axis through puberty. This study aimed to establish a normal range for urinary gonadotrophins in children progressing through puberty. Methods Urine samples were collected from 161 healthy school children (76 boys, 85 girls) aged 4–19 yrs. Height and weight were converted to standard deviation score. Pubertal status, classified by Tanner staging, was determined by self-assessment. Urinary gonadotrophins were measured by chemiluminescent microparticle immunoassay. Results were grouped according to pubertal status (pre-pubertal or pubertal). Results Of the 161 children, 50 were pre-pubertal (28 boys; 22 girls) and 111 were pubertal (48 boys; 63 girls). Overall, urinary gonadotrophins concentrations increased with pubertal maturation. All pre-pubertal children had a low urinary LH:Creatinine ratio. LH:Creatinine ratios were significantly higher in pubertal compared to pre-pubertal boys (pp = 0.006). However, LH:FSH ratios were a more consistent discriminant between pre-pubertal and pubertal states in both sexes (Boys 0.45 pubertal vs 0.1 pre-pubertal; girls 0.23 pubertal vs 0.06 pre-pubertal). Conclusion Urinary gonadotrophins analyses could be used as non-invasive integrated measurement of pubertal status which reflects clinical/physical status.
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- 2012
155. Inflammation and linear bone growth: the inhibitory role of SOCS2 on GH/IGF-1 signaling
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Colin Farquharson and S Faisal Ahmed
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medicine.medical_specialty ,medicine.medical_treatment ,Inflammation ,Suppressor of Cytokine Signaling Proteins ,Complement factor I ,Bone and Bones ,Proinflammatory cytokine ,Internal medicine ,Medicine ,Animals ,Humans ,Growth Plate ,Insulin-Like Growth Factor I ,Renal Insufficiency, Chronic ,SOCS2 ,Growth Disorders ,Bone growth ,Bone Development ,business.industry ,Human Growth Hormone ,medicine.disease ,Body Height ,Endocrinology ,Cytokine ,Nephrology ,Pediatrics, Perinatology and Child Health ,Linear Models ,Cytokines ,medicine.symptom ,Signal transduction ,Inflammation Mediators ,business ,Kidney disease ,Signal Transduction - Abstract
Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function.
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- 2012
156. SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis
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Chloe Pass, Carmen Huesa, Colin Farquharson, S Faisal Ahmed, and Vicky E MacRae
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Male ,medicine.medical_specialty ,Genotype ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Blotting, Western ,Suppressor of Cytokine Signaling Proteins ,Biology ,Polymerase Chain Reaction ,Chondrocyte ,Mice ,Chondrocytes ,Internal medicine ,medicine ,Animals ,Orthopedics and Sports Medicine ,SOCS3 ,Growth Plate ,Insulin-Like Growth Factor I ,Phosphorylation ,SOCS2 ,Cells, Cultured ,Metatarsal Bones ,Cell Proliferation ,Bone growth ,Mice, Knockout ,Suppressor of cytokine signaling 1 ,Growth factor ,Gene Expression Regulation, Developmental ,Chondrogenesis ,Immunohistochemistry ,STAT Transcription Factors ,medicine.anatomical_structure ,Endocrinology ,Growth Hormone ,Janus kinase ,Signal Transduction - Abstract
Suppressor of Cytokine Signaling-2 (SOCS2) is a negative regulator of growth hormone (GH) signaling and bone growth via inhibition of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. This has been classically demonstrated by the overgrowth phenotype of SOCS2(-/-) mice, which has normal systemic insulin-like growth factor 1 (IGF-1) levels. The local effects of GH on bone growth are equivocal, and therefore this study aimed to understand better the SOCS2 signaling mechanisms mediating the local actions of GH on epiphyseal chondrocytes and bone growth. SOCS2, in contrast to SOCS1 and SOCS3 expression, was increased in cultured chondrocytes after GH challenge. Gain- and loss-of-function studies indicated that GH-stimulated chondrocyte STATs-1, -3, and -5 phosphorylation was increased in SOCS2(-/-) chondrocytes but not in cells overexpressing SOCS2. This increased chondrocyte STAT signaling in the absence of SOCS2 is likely to explain the observed GH stimulation of longitudinal growth of cultured SOCS2(-/-) embryonic metatarsals and the proliferation of chondrocytes within. Consistent with this metatarsal data, bone growth rates, growth plate widths, and chondrocyte proliferation were all increased in SOCS2(-/-) 6-week-old mice as was the number of phosphorylated STAT-5-positive hypertrophic chondrocytes. The SOCS2(-/-) mouse represents a valid model for studying the local effects of GH on bone growth.
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- 2012
157. Identification and management of poor response to growth-promoting therapy in children with short stature
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Régis Coutant, Ron G. Rosenfeld, S Faisal Ahmed, Jesús Argente, Philippe Backeljauw, Peter Bang, Markus Bettendorf, M.J.E. Walenkamp, Martin O. Savage, Gianni Bona, Pediatric surgery, and Other Research
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medicine.medical_specialty ,Pediatrics ,Medicin och hälsovetenskap ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Growth hormone ,Short stature ,Medical and Health Sciences ,Endocrinology ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Child ,Growth Disorders ,High rate ,Growth promoting ,Treatment regimen ,business.industry ,Body Height ,The primary diagnosis ,Discontinuation ,Treatment Outcome ,Child, Preschool ,Growth Hormone ,medicine.symptom ,business - Abstract
Growth hormone (GH) is widely prescribed for children with short stature across a range of growth disorders. Recombinant human (rh) insulin-like growth factor-1 (rhIGF-1) therapy is approved for severe primary IGF-I deficiency - a state of severe GH resistance. Evidence is increasing for an unacceptably high rate of poor or unsatisfactory response to growth-promoting therapy (i.e. not leading to significant catch up growth) in terms of change in height standard deviation score (SDS) and height velocity (HV) in many approved indications. Consequently, there is a need to define poor response and to prevent or correct it by optimizing treatment regimens within accepted guidelines. Recognition of a poor response is an indication for action by the treating physician, either to modify the therapy or to review the primary diagnosis leading either to discontinuation or change of therapy. This review discusses the optimal investigation of the child who is a candidate for GH or IGF-1 therapy so that a diagnosis-based choice of therapy and dosage can be made. The relevant parameters in the evaluation of growth response are described together with the definitions of poor response. Prevention of poor response is addressed by discussion of strategy for first-year management with GH and IGF-1. Adherence to therapy is reviewed as is the recommended action following the identification of the poorly responding patient. The awareness, recognition and management of poor response to growth-promoting therapy will lead to better patient care, greater cost-effectiveness and increased opportunities for clinical benefit.
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- 2012
158. E-consultation for DSD: a global platform for access to expert advice
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Stenvert L. S. Drop, Alaa El-Ghoneimi, S Faisal Ahmed, Pierre-Yves Mure, Dan Wood, and Pediatrics
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Male ,Service (systems architecture) ,Telemedicine ,Knowledge management ,Consultants ,Urology ,Expert advice ,Disorders of Sex Development ,Telehealth ,Global Health ,Pediatric Assistants ,03 medical and health sciences ,0302 clinical medicine ,Health care ,Medicine ,Humans ,030212 general & internal medicine ,Child ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,E consultation ,Data collection ,business.industry ,Electronic consultation ,3. Good health ,Pediatrics, Perinatology and Child Health ,Female ,business - Abstract
Electronic consultation (e-consultation) has been used for some years to facilitate communication between patients and their doctors, but it is also emerging as a valuable tool aiding communication between clinicians, both primary care and specialists, about a patient's care. Telehealth systems are being developed to provide video consultations to support diagnosis and management, as well as supporting clinical networks and health professional education. In some world regions, it seems increasingly likely that most rare diseases will be managed through a network of centres of expertise, and e-consultation systems may become a vital component of the service provided by these networks. Long-distance consultation across geographical and national boundaries has been used between colleagues in DSD for many years. However, the development of a robust and secure e-consultation service within the international DSD community appears to be timely. It will extend the current database and e-learning facilities, and should be achieved with the objective of providing expert opinion on a worldwide basis. It is proposed to install a steering committee to oversee the various practical, legal and cultural issues setting standards on data collection and exchange. The opportunity to broaden access to healthcare for all DSD patients and to widen discussion across the DSD community is valuable, and it is the view of the authors that this should be pursued and developed.
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- 2012
159. Management of differences and disorders of sex development in the newborn
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S. Faisal Ahmed, Paula Midgley, and Martina Rodie
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The birth of a new baby is one of the greatest wonders of nature. The first question that is usually posed by the new parent is 'is it a boy or a girl?'; without this information the parents cannot even formulate the second question, which is usually 'is he/she alright?'. It is no wonder that the birth of a child with an abnormality of genital development where the sex of rearing is uncertain at birth, presents difficult clinical and ethical issues. However, the recognition of genital ambiguity may depend on the expertise of the observer. The prevalence of genital anomalies at birth may be as high as 1 in 300 births (1), the prevalence of complex anomalies that may lead to true genital ambiguity may be as low as 1 in 5000 births (2). Rather than treating every affected child as a medical emergency, it is paramount that such a child is first assessed by an expert with adequate knowledge about the range of variation in the physical appearance of genitalia, the underlying pathophysiology of disorders of sex development, and the strengths and weaknesses of the tests that can be performed in early infancy. This expert should be able to ensure that the parents’ needs for information are comprehensively addressed, while appropriate investigations are performed in a timely fashion. This expert also needs to have immediate access to the multidisciplinary team that is essential for the management of such a child. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.
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- 2011
160. A preliminary trial of the effect of recombinant human growth hormone on short-term linear growth and glucose homeostasis in children with Crohn's disease
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S C, Wong, P, Kumar, P J, Galloway, J C, Blair, M, Didi, A M, Dalzell, K, Hassan, P, McGrogan, and S Faisal, Ahmed
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Male ,Adolescent ,Human Growth Hormone ,Prednisolone ,Body Height ,Recombinant Proteins ,Enteral Nutrition ,Glucose ,Crohn Disease ,Homeostasis ,Humans ,Insulin ,Female ,Child - Abstract
It is unclear whether recombinant human growth hormone (rhGH) improves linear growth in children with Crohn's disease (CD).To investigate the effects of rhGH on height velocity (HV) and glucose homeostasis over a 6-month period.Randomized controlled trial in two tertiary children's hospitals in 22 children with inflammatory bowel disease amongst whom 21 had CD. Duration of disease from diagnosis and number of acute relapses requiring either exclusive enteral nutrition or therapeutic dose of oral prednisolone were similar in the treatment and control groups.Either rhGH (0·067 mg/kg per day) as daily subcutaneous injections (rhGH group; n, 11) or no rhGH, (Ctrl; n, 11) for 6 months.Percentage change in HV after 6 months in the two groups. Auxology, puberty, skeletal age, disease factors, treatment and glucose homeostasis were also assessed.Median HV increased from 4·5 (range, 0·6, 8·9) at baseline to 10·8 (6·1, 15·0) cm/year at 6 month (P = 0·003) in the rhGH group, whereas in the Ctrl group, it was 3·8 (1·4, 6·7) and 3·5 cm/year (2·0, 9·6), respectively (P = 0·58). Median percentage increase in HV after 6 months in the rhGH group was 140% (16·7, 916·7) compared with 17·4% (-42·1%, 97·7%) in the Ctrl group (P0·001). There were no significant differences in disease activity and proinflammatory cytokines at baseline and 6 months in both groups and change in bone age for chronological age was also similar in the two groups. In the rhGH group, fasting insulin increased from 4·0 (2·0, 11·0) to 7·0 mU/l (2·0, 16·0) (P = 0·02), whereas in the Ctrl group, it was 3·0 (1·2, 12·7) and 3·8 mU/l (2·1, 7·0) (P = 0·72), respectively.Although this pilot trial shows that rhGH can improve short-term linear growth in children with CD, the clinical efficacy of this therapy needs to be further studied in longer-term studies of growth, glucose homeostasis and disease status.
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- 2011
161. Investment supervision in stock market
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Umm-e-Laila, Abdul Raees, S. Faisal Ahmed Bukhari, and Umm-e-Farwa
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Market capitalization ,Finance ,Unit investment trust ,business.industry ,Order (exchange) ,Return on investment ,Corporate governance ,Stock market ,business ,Investment (macroeconomics) ,Open-ended investment company - Abstract
Stock market plays a vital role in country's economy and financial system. It has many impacts on the economy like raising capital for businesses, aiding company growth, corporate governance, mobilizing savings for the investment, reallocation of wealth, government capital-raising for development. In stock market the investors are normally dependent on brokers for appropriate selection of shares for buying and selling. These dependencies normally have many issues like brokerage, monopoly of broker. In order to reduce dependency on the broker, a model is proposed for investment supervision that will help investor to find out the possible trends in shares for future investment. This model is used to analyzes the past financial statements of a company and it shows effectiveness of the company's share. On behalf of the results the user can take decisions for future investment in that company. This model uses ratio analysis for analyzing the financial statements.
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- 2010
162. WT1 mutations in Meacham syndrome suggest a coelomic mesothelial origin of the cardiac and diaphragmatic malformations
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Shirley I. Smith, Peter Kelehan, Wayne Lam, John Tolmie, Mohnish Suri, David O'Neill, Emma McCann, Shantala Vadeyar, William Reardon, S Faisal Ahmed, David R. FitzPatrick, Judith Grant, and Nicholas D. Hastie
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Heart Defects, Congenital ,medicine.medical_specialty ,Candidate gene ,Pathology ,Genes, Wilms Tumor ,Diaphragm ,Uterus ,Biology ,Epithelium ,Internal medicine ,Genetics ,medicine ,Missense mutation ,Humans ,Diaphragmatic hernia ,Genetics (clinical) ,urogenital system ,fungi ,Infant, Newborn ,Wilms' tumor ,Syndrome ,medicine.disease ,Phenotype ,Mesothelium ,Endocrinology ,medicine.anatomical_structure ,Male pseudohermaphroditism ,Mutation - Abstract
Meacham syndrome is a rare sporadically occurring multiple malformation syndrome characterized by male pseudohermaphroditism with abnormal internal female genitalia comprising a uterus and double or septate vagina, complex congenital heart defect and diaphragmatic abnormalities. We report on eight new cases of this condition, two of whom were shown to have heterozygous missense mutations in the C-terminal zinc finger domains of WT1: Arg366Cys and Arg394Trp. These data represent clinical and molecular evidence that the WT1 gene plays a central role in normal development of the diaphragm and the proepicardially derived tissues. Identification of WT1 expression in the region of coelomic mesothelium which will form the proepicardium and diaphragm provides a plausible unifying patterning defect in these cases. Interestingly, the Arg366Cys mutation has been previously reported in Denys–Drash syndrome and Arg394Trp mutation has been previously reported in both isolated Wilms tumor and Denys–Drash syndrome. This phenotypic diversity with a single mutation suggests there are other factors modulating all aspects of WT1 function during human development. If genetic modifiers of WT1 can be identified in animal models these become good candidate genes for the cases with Meacham syndrome we report on here where WT1 mutations cannot be identified. © 2007 Wiley-Liss, Inc.
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- 2007
163. Functional characterization of GATA3 mutations causing the hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome: insight into mechanisms of DNA binding by the GATA3 transcription factor
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Paul T. Christie, Encarna Guillén-Navarro, S Faisal Ahmed, Zulf Mughal, Asif Ali, Albert C.M. Ong, Hilde Van Esch, Brian Harding, Geoffrey N. Hendy, M. Andrew Nesbit, Patricia Christin, Irina V. Grigorieva, Jozef Gecz, Eberhard Blind, Peter E. Clayton, Sarah F. Smithson, Fiona Lalloo, Christoph J. Mache, Catherine Bloch, Brigitte Gilbert-Dussardier, Nicholas Shaw, Anna Hackett, Isil Halac, Choni Rinat, Rajesh V. Thakker, Jacques Weill, Maria Bitner-Glindzicz, and John Tolmie
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Adult ,Male ,Models, Molecular ,Adolescent ,Hypoparathyroidism ,Nonsense mutation ,Molecular Sequence Data ,GATA3 Transcription Factor ,Biology ,Deafness ,medicine.disease_cause ,Kidney ,Models, Biological ,Frameshift mutation ,Germline mutation ,Genetics ,medicine ,Missense mutation ,Humans ,Abnormalities, Multiple ,Amino Acid Sequence ,Child ,Molecular Biology ,Genetics (clinical) ,Zinc finger transcription factor ,Zinc finger ,Mutation ,Splice site mutation ,Base Sequence ,Infant, Newborn ,Infant ,General Medicine ,Syndrome ,Pedigree ,DNA-Binding Proteins ,Child, Preschool ,Female ,RNA Splice Sites - Abstract
The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous germline mutations were identified in patients with HDR. These consisted of three nonsense mutations, six frameshifting deletions, two frameshifting insertions, one missense (Leu348Arg) mutation and one acceptor splice site mutation. The splice site mutation was demonstrated to cause a pre-mRNA processing abnormality leading to the use of an alternative acceptor site 8 bp downstream of the normal site, resulting in a frameshift and prematurely terminated protein. Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3 mutations: those that lead to a loss of DNA binding which represent over 90% of all mutations, and involved a loss of the carboxy-terminal zinc finger; those that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that did not alter DNA binding or the affinity but likely altered the conformational change that occurs during binding in the DNA major groove as predicted by a three-dimensional modeling. These results elucidate further the molecular mechanisms underlying the altered functions of mutants of this zinc finger transcription factor and their role in causing this developmental anomaly. No mutations were identified in patients with isolated hypoparathyroidism, thereby indicating that GATA3 abnormalities are more likely to result in two or more of the phenotypic features of the HDR syndrome and not in one, such as isolated hypoparathyroidism.
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- 2007
164. Consensus statement on management of intersex disorders. International Consensus Conference on Intersex
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Peter A, Lee, Christopher P, Houk, S Faisal, Ahmed, and Ieuan A, Hughes
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Counseling ,Gonadal Dysgenesis, 46,XY ,Male ,Parents ,Sexual Behavior ,Disorders of Sex Development ,Infant, Newborn ,Gender Identity ,Neoplasms, Germ Cell and Embryonal ,Combined Modality Therapy ,Phenotype ,Treatment Outcome ,Terminology as Topic ,Humans ,Psychology ,Female ,Genetic Predisposition to Disease ,Gonadal Steroid Hormones ,Attitude to Health ,Case Management ,Forecasting - Published
- 2006
165. Summary of consensus statement on intersex disorders and their management. International Intersex Consensus Conference
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Christopher P, Houk, Ieuan A, Hughes, S Faisal, Ahmed, and Peter A, Lee
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Counseling ,Gonadal Dysgenesis, 46,XY ,Male ,Parents ,Sexual Behavior ,Disorders of Sex Development ,Infant, Newborn ,Gender Identity ,Neoplasms, Germ Cell and Embryonal ,Combined Modality Therapy ,Phenotype ,Treatment Outcome ,Terminology as Topic ,Humans ,Psychology ,Female ,Genetic Predisposition to Disease ,Gonadal Steroid Hormones ,Attitude to Health ,Case Management ,Forecasting - Published
- 2006
166. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome
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Melissa, Hines, S Faisal, Ahmed, and Ieuan A, Hughes
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Adult ,Male ,Time Factors ,Adolescent ,Sexual Behavior ,Gender Identity ,Androgen-Insensitivity Syndrome ,Self Concept ,Personality Development ,Sex Factors ,Risk Factors ,Case-Control Studies ,Surveys and Questionnaires ,Adaptation, Psychological ,Humans ,Female ,Life Style - Abstract
We evaluated psychological outcomes and gender development in 22 women with complete androgen insensitivity syndrome (CAIS). Participants were recruited through a medical database (n = 10) or through a patient support group (n = 12). Controls included 14 males and 33 females, of whom 22 were matched to women with CAIS for age, race, and sex-of-rearing. Outcome measures included quality of life (self-esteem and psychological general well-being), gender-related psychological characteristics (gender identity, sexual orientation, and gender role behavior in childhood and adulthood), marital status, personality traits that show sex differences, and hand preferences. Women recruited through the database versus the support group did not differ systematically, and there were no statistically significant differences between the 22 women with CAIS and the matched controls for any psychological outcome. These findings argue against the need for two X chromosomes or ovaries to determine feminine-typical psychological development in humans and reinforce the important role of the androgen receptor in influencing masculine-typical psychological development. They also suggest that psychological outcomes in women with CAIS are similar to those in other women. However, additional attention to more detailed aspects of psychological well-being in CAIS is needed.
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- 2003
167. Skeletal disproportion in children with chronic renal disease
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T. James Beattie, Lolita Alcocer, Ian J. Ramage, S Faisal Ahmed, Nadia Qayyum, Heather Maxwell, and Anna V. Murphy
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Short stature ,Endocrinology ,medicine ,Prevalence ,Humans ,Longitudinal Studies ,Child ,Growth Disorders ,Anthropometry ,business.industry ,Human Growth Hormone ,Chronic renal disease ,Kidney Transplantation ,Body Height ,Sitting height ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Physical therapy ,Kidney Failure, Chronic ,Regression Analysis ,Female ,medicine.symptom ,business - Abstract
Objectives: To assess stature and skeletal disproportion in children with chronic renal disease. Methods: Cross-sectional study of height (HT), sitting height (SH), subischial leg length (SILL), sitting height/height ratio (SH:HT) and disproportion score (SH SDS minus SILL SDS) in 56 children (M:35) with median age 11.4 years (range 4.5,18.7) with chronic renal disease. Results: There were 19 children with chronic renal insufficiency, 6 receiving peritoneal dialysis and 31 after renal transplant. The median HTSDS for the whole group was –1.21 (–2.8, 0.35). The median SH:HT ratio in non-transplanted children and renal transplant were 0.51 (0.49, 0.53) and 0.50 (0.48, 0.53), respectively (p = 0.02). The median disproportion score of the whole group was –3.2 (–4.8, –1.8). There was a significant correlation between disproportion score and SH:HT (r = 0.5, p = 0.005). SH:HT ratio was negatively related to duration of illness (r = 0.4, p = 0.005). Conclusion: Children with chronic renal disease have significant body disproportion and this may be due to a disproportionately greater effect of disease and treatment on spinal growth.
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- 2002
168. The genetics of male undermasculinization
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S Faisal, Ahmed and Ieuan A, Hughes
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Male ,Embryonic and Fetal Development ,Mice ,Sex Differentiation ,Genes ,Models, Animal ,Testis ,Disorders of Sex Development ,Animals ,Humans ,Gestational Age ,Testosterone ,Genitalia, Male - Abstract
A review of the genetics of male undermasculinization must encompass a description of the embryology of the genital system. The dimorphism of sex development consequent upon the formation of a testis and the subsequent secretion of hormones to impose a male phenotype is highlighted. Thus, an understanding of the causes of male undermasculinization (manifest as XY sex reversal, complete and partial) includes reviewing the genetic factors which control testis determination and the production and action of testicular hormones. The study of disorders of male sex development has contributed substantially to knowledge of normal male development before birth. This knowledge has been complimented in recent years by the use of targeted murine gene disruption experiments to study the sex phenotype, although murine and human phenotypes are not always concordant. The investigation of disorders associated with male undermasculinization of prenatal onset is described briefly to complete the review.
- Published
- 2002
169. PTEN mutation spectrum and genotype-phenotype correlations in Bannayan-Riley-Ruvalcaba syndrome suggest a single entity with Cowden syndrome
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Corrado Romano, Richard C. Trembath, Elaine H. Zackai, Charis Eng, Michael J. Bennett, Carol A. Crowe, John Tolmie, Katherine L. Nathanson, Teresa M. Dunn, David K. Manchester, Majed Dasouki, Robert J. Gorlin, Bruce R. Korf, Liang Ping Weng, Shirley Hodgson, Patricia L. M. Dahia, Robin M. Winter, Alasdair G. W. Hunter, Victoria Murday, Jennifer B. Kum, John M. Graham, S Faisal Ahmed, Kathryn L. Lunetta, Roberto T. Zori, Howard Feit, Joann Bodurtha, Michael T. Geraghty, Susan Miesfeldt, Deborah J. Marsh, Melissa A. Parisi, Mary Curtis, and Barbara R. Pober
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Genetic Markers ,Male ,Heterozygote ,Tumor suppressor gene ,Genotype ,medicine.disease_cause ,Cohort Studies ,Craniofacial Abnormalities ,Bannayan–Riley–Ruvalcaba syndrome ,Germline mutation ,Intellectual Disability ,Genetics ,medicine ,PTEN ,Humans ,Abnormalities, Multiple ,Molecular Biology ,Genetics (clinical) ,Cells, Cultured ,Germ-Line Mutation ,Family Health ,Mutation ,Mutation Spectra ,biology ,Chromosomes, Human, Pair 10 ,Genetic Carrier Screening ,Tumor Suppressor Proteins ,Macrocephaly ,PTEN Phosphohydrolase ,Chromosome Mapping ,General Medicine ,Cowden syndrome ,Syndrome ,medicine.disease ,Phosphoric Monoester Hydrolases ,Pedigree ,Phenotype ,biology.protein ,Cancer research ,Female ,medicine.symptom ,Chromosome Deletion ,Hamartoma Syndrome, Multiple - Abstract
Germline mutations in the tumour suppressor gene PTEN have been implicated in two hamartoma syndromes that exhibit some clinical overlap, Cowden syndrome (CS) and Bannayan-Riley-Ruvalcaba syndrome (BRR). PTEN maps to 10q23 and encodes a dual specificity phosphatase, a substrate of which is phosphatidylinositol 3,4,5-triphosphate, a phospholipid in the phosphatidylinositol 3-kinase pathway. CS is characterized by multiple hamartomas and an increased risk of benign and malignant disease of the breast, thyroid and central nervous system, whilst the presence of cancer has not been formally documented in BRR. The partial clinical overlap in these two syndromes is exemplified by the hallmark features of BRR: macrocephaly and multiple lipomas, the latter of which occur in a minority of individuals with CS. Additional features observed in BRR, which may also occur in a minority of CS patients, include Hashimoto's thyroiditis, vascular malformations and mental retardation. Pigmented macules of the glans penis, delayed motor development and neonatal or infant onset are noted only in BRR. In this study, constitutive DNA samples from 43 BRR individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both CS and BRR, were screened for PTEN mutations. Mutations were identified in 26 of 43 (60%) BRR cases. Genotype-phenotype analyses within the BRR group suggested a number of correlations, including the association of PTEN mutation and cancer or breast fibroadenoma in any given CS, BRR or BRR/CS overlap family ( P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family ( P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRR patients ( P = 0.028). In contrast to a prior report, no significant difference in mutation status was found in familial versus sporadic cases of BRR ( P = 0.113). Comparisons between BRR and a previously studied group of 37 CS families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CS alone or both CS and BRR when compared with BRR alone ( P = 0.002). Among CS, BRR and BRR/CS overlap families that are PTEN mutation positive, the mutation spectra appear similar. Thus, PTEN mutation-positive CS and BRR may be different presentations of a single syndrome and, hence, both should receive equal attention with respect to cancer surveillance.
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- 1999
170. Sexual dimorphism in the neonatal gonad
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N Coleman, A Cheng, Han N. Lim, J.R. Hawkins, K L Ng, S Faisal Ahmed, and Ieuan A. Hughes
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Male ,endocrine system ,medicine.medical_specialty ,Gonad ,Ovary ,Endocrine System ,Embryonic and Fetal Development ,Internal medicine ,Y Chromosome ,Testis ,medicine ,Humans ,Aromatase ,Testosterone ,Sex Characteristics ,biology ,Gonadal ridge ,luteinizing hormone/choriogonadotropin receptor ,Infant, Newborn ,General Medicine ,Sex Determination Processes ,medicine.anatomical_structure ,Endocrinology ,Pediatrics, Perinatology and Child Health ,biology.protein ,Female ,Luteinizing hormone ,Germ cell - Abstract
The neonatal gonad has two distinct forms (i.e., is sexually dimorphic), as judged by morphological and endocrine characteristics. The dimorphic process begins early in embryogenesis. It is well established by the time of birth, by which time the genital ridge has developed into either a testis or an ovary. The mechanisms involved in sex determination involve the Y chromosome, autosomal genes, transcription factors and possibly other unidentified control networks. This review paper describes the morphological changes that occur and the endocrine functions in the developing gonads. It highlights a number of important differences in fetal and neonatal gonadal function. The testis has early histological definition, several determining genes, delayed germ cell maturation, early autonomous steroid secretion, luteinizing hormone (LH) receptor and steroid enzyme expression, high fetal testicular testosterone content, prominent postnatal Leydig and Sertoli cells and high postnatal serum testosterone levels. The ovary has a prolonged monomorphic state, probably one determining gene, germ cells in early meiotic arrest, delayed expression of LH receptor and aromatase, low ovarian oestradiol content, prominent postnatal follicles and low postnatal serum oestradiol levels.
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- 1999
171. The spectrum of associated congenital anomalies in disorders of sex development: a review of the I-DSD Registry
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Kathryn Cox, Antonio Balsamo, Wiebke Arlt, S Faisal Ahmed, Richard O. Sinnott, Feyza Darendeliler, Ieuan A. Hughes, Mona Ellaithi, Olle Söder, Martina Rodie, Jipu Jiang, Stenvert L. S. Drop, Lidka Lisa, Yves Morel, Jillian Bryce, Silvano Bertelloni, Martine Cools, Mona Alkhawari, Olaf Hiort, and Laura Audí
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Pediatrics ,medicine.medical_specialty ,business.industry ,medicine ,Disorders of sex development ,medicine.disease ,business - Published
- 2013
172. Characterising changes in the in vivo male rodent brain using magnetic resonance spectroscopy
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Lindsay Gallagher, William M. Holmes, Michelle Welsh, I. Mhairi Macrae, S Faisal Ahmed, Jim Mullin, Martina Rodie, and Martin McMillan
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Nuclear magnetic resonance ,Rodent ,biology ,Chemistry ,In vivo ,biology.animal ,Nuclear magnetic resonance spectroscopy - Published
- 2013
173. Growth Disorders
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S. Faisal Ahmed
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business.industry ,Medicine ,General Medicine ,business ,Humanities - Published
- 2008
174. Subject Index Vol. 68, Suppl. 5, 2007
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Bessie E. Spiliotis, Mary P. Gillam, Klaus Mann, Barney Harrison, Anthony P. Heaney, Wiebke Arlt, Ieuan A. Hughes, F. Péter, V. Radonsky, D. Damiani, Felix Casanueva, Wim Van Hul, Elena Livadariu, H. Cabral de Menezes Filho, E. Sólyom, Allan E. Herbison, Peter J Trainer, M. C. Burlacu, Felix Beuschlein, Sabine M.P.F. de Muinck Keizer-Schrama, Amar Agha, Ulla Feldt-Rasmussen, Stanko Skrtic, Wayne S. Cutfield, Annette Grüters, David R. Clemmons, Francis H. Glorieux, J. Sudagani, A. Muzsnai, Patrick Wilton, Robert C. Tasker, Dana S. Hardin, Paul Czernichow, Friedhelm Raue, Hans Lennernäs, S. Aylwin, Georgios Karagiannis, Sadaf Farooqi, M.B. Ranke, Maithé Tauber, Karin Frank-Raue, Mehul T. Dattani, H. Kuperman, S. Dewan, Michael Buchfelder, A. Mukherjee, Feyza Darendeliler, C. Taylor, David B. Dunger, Gudmundur Johannsson, Christian J. Strasburger, Gerard S. Conway, I.M. Holdaway, A. Lecka, Adrian F. Daly, Heiko Krude, T. Della Manna, Paraic McGrogan, I. Ilyés, J. Prague, Lauri A. Aaltonen, Daniel Kelberman, V. Dichtchekenian, Claus Højbjerg Gravholt, J.M. Rodrigues, Günter K. Stalla, Helmuth G. Dörr, Jens Sandahl Christiansen, Kees Noordam, Kirstine Stochholm, Ragnhildur Bergthorsdottir, T. Kearney, A. McGregor, Kenji Fujieda, Martin O. Savage, K. Gnanalingham, J. Kovács, Helena Filipsson, Michael Droste, Hans P.F. Koppeschaar, Clifford J. Rosen, J. Miell, Dominique Simon, Mitchell E. Geffner, Ezio Ghigo, Torben Laursen, Lucy Ann Behan, L. Steinmetz, Akira Shimatsu, Jarod S.C. Wong, Andy Toogood, Carlo L. Acerini, Theo J. Visser, Aldo Pinchera, Berthold P. Hauffa, Niki Karavitaki, T. Niederland, N. Setian, Albert Beckers, Phyllis W. Speiser, Nils Krone, Mark E. Molitch, Mauro Bozzola, S Faisal Ahmed, D. Kannappan, J. Sólyom, V. Oguntolu, J.P.H. Shield, Y. Al-Zaman, Beverly M. K. Biller, and Bernhard Saller
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Endocrinology ,Index (economics) ,Endocrinology, Diabetes and Metabolism ,Pediatrics, Perinatology and Child Health ,Statistics ,Subject (documents) ,Psychology - Published
- 2007
175. Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021)
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Leslie Perry, Naomi S Crouch, Helen E. Turner, Stuart O'Toole, John C. Achermann, Martina Rodie, Sue Elford, Ruth McGowan, Julie Alderson, Talat Mushtaq, Mars Skae, Ieuan A. Hughes, Nils Krone, S Faisal Ahmed, Ahmed, S Faisal [0000-0003-0689-5549], Achermann, John [0000-0001-8787-6272], and Apollo - University of Cambridge Repository
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Parents ,puberty ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Disorders of Sex Development ,DSD ,030209 endocrinology & metabolism ,03 medical and health sciences ,Nursing care ,0302 clinical medicine ,Endocrinology ,Multidisciplinary approach ,Internal medicine ,medicine ,Humans ,gonads ,Child ,Service (business) ,business.industry ,Sexual Development ,Paediatric endocrinologist ,genitalia ,Diagnostic test ,United Kingdom ,030220 oncology & carcinogenesis ,business ,Young person - Abstract
It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion. Finally, for rare conditions such as these, it is imperative that clinical experience is shared through national and international clinical and research collaborations.
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176. Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis
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Nicole Reisch, Stefanie Hahner, Johan G. Beun, Manuela Brösamle, Henrik Falhammar, Irina Chifu, Hedi Claahsen van der Grinten, S Faisal Ahmed, Svetlana Lajic, Sophie Bensing, Jette Kristensen, Eystein S. Husebye, Paola Loli, Hanna F. Nowotny, and Maria Clemente
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medicine.medical_specialty ,Hydrocortisone ,Hormone Replacement Therapy ,Endocrinology, Diabetes and Metabolism ,Mini Review ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,medicine ,Adrenal insufficiency ,Humans ,Endocrine system ,Glucocorticoid replacement ,Congenital adrenal hyperplasia ,Hormone replacement therapy ,Adverse effect ,Intensive care medicine ,Glucocorticoids ,business.industry ,Adrenal crisis ,Stress instructions ,medicine.disease ,Europe ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,Glucocorticoid ,medicine.drug - Abstract
Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives.
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177. Salivary androgens in adolescence and their value as a marker of puberty: results from the SCAMP cohort
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Supitcha Patjamontri, Alexander Spiers, Rachel B Smith, Chen Shen, Jo Adaway, Brian G Keevil, Mireille B Toledano, and S Faisal Ahmed
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androstenedione ,liquid chromatographymass spectrometry (lc-msms) ,pubertal development scale (pds) ,saliva ,testosterone ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Context: Salivary androgens represent non-invasive biomarkers of puberty that may have utility in clinical and population studies. Objective: To understand normal age-related variation in salivary sex steroids and demonstrate their correlation to pubertal development in young adolescents. Design, setting and participants: School-based cohort study of 1495 adolescents at two time points for collecting saliva samples approximately 2 years apart. Outcome measures: The saliva samples were analyzed for five androgens (testostero ne, androstenedione (A4), 17-hydroxyprogesterone, 11-ketotestosterone and 11β-hydroxyandrostenedione) using liquid chromatography-mass spectrometry; in addition, salivary dehydroepiandrosterone (DHEA) and oestradiol (OE2) were analysed by ELISA. The pubertal staging was self-reported using the Pubertal Development Scale (PDS). Results: In 1236 saliva samples from 903 boys aged between 11 and 16 years, salivary androgens except DHEA exhibited an increasing trend with an advancing age (ANOVA, P < 0.001), with salivary testosterone and A4 concentration showing the strongest correlation (r = 0.55, P < 0.001 and r = 0.48, P < 0.001, respectively). In a subgroup analysis of 155 and 63 saliva samples in boys and girls, respectively, morning salivary testosterone concentrations showed the highest correlation with composite PDS scores and voice-breaking category from PDS self-report in boys (r = 0.75, r = 0.67, respectively). In girls, salivary DHEA and OE2 had negligible correlations with age or composite PDS scores. Conclusion: In boys aged 11–16 years, an increase in salivary testosterone and A4 is associated with self-reported pubertal progress and represents valid non-invasive biomarkers of puberty in boys.
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- 2023
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178. New cases of rare bone and mineral conditions reported within the first 18 months of the European registry for rare bone and mineral conditions
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Ana Luisa Priego Zurita, Jillian Bryce, Inês Alves, Manila Boarini, Corinna Grasemann, Wolfgang Högler, M. Kassim Javaid, Agnès Linglart, Klaus Mohnike, Marina Mordenti, Geert Mortier, Marco Roos, Luca Sangiorgi, Rebecca Skarberg, Ondrej Soucek, S. Faisal Ahmed, and Natasha Appelman-Dijkstra
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Endocrinology, Diabetes and Metabolism ,Orthopedics and Sports Medicine - Full Text
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179. Predictors of surgical complications in boys with hypospadias: data from an international registry
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Tim Cheetham, Sukran Poyrazoglu, Justin H Davies, S Faisal Ahmed, Jillian Bryce, Anna Nordenström, Angela K Lucas-Herald, Paul-Martin Holterhus, Marcio Lopes Miranda, Stuart O’Toole, Eduardo Corrêa Costa, Kathryn Scougall, Federico Baronio, Rachel L Boal, Jose Roberto Castera, Sebastián Castro, Feyza Darendeliler, Mirjam Dirlewanger, Gabriella Gazdagh, Evgenia Globa, Gil Guerra-Junior, Tulay Guran, Gloria Herrmann, Ahsen Karagözlü Akgül, Renata Markosyan, Kenneth McElreavey, Gianni Russo, Valerie Schwitzgebel, Marianna Stancampiano, and Michael Steigert
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Pediatrics ,RJ1-570 ,Surgery ,RD1-811 - Abstract
Background Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence.Methods Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher’s exact tests and spearman’s correlation tests were performed on the data to assess associations between clinical factors and complication rates.Results Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications.Conclusions Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.
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- 2023
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180. Starting point for benchmarking outcomes and reporting of pituitary adenoma surgery within the European Reference Network on Rare Endocrine Conditions (Endo-ERN): results from a meta-analysis and survey study
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Amir H Zamanipoor Najafabadi, Merel van der Meulen, Ana Luisa Priego Zurita, S Faisal Ahmed, Wouter R van Furth, Evangelia Charmandari, Olaf Hiort, Alberto M Pereira, Mehul Dattani, Diana Vitali, Johan P de Graaf, and Nienke R Biermasz
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endo-ern ,pituitary ,surgery ,registry ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, inc luding care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pi tuitary adenoma within Endo-ERN. Design and Methods: Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by refere nce centers on their current surgical practice. Results: A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6- represented countries published 48 articles. Remission rates we re 50% (95% CI: 42–59) for patients with acromegaly, 68% (95% CI: 60–75) for Cushing’s disease, and 53% (95% CI: 39–66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37–61%) of patients and visual improvement in 78% (95% CI: 68–87). Mort ality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11–23), transient diabetes insipidus in 12% (95 % CI: 6–21), permanent diabetes insipidus in 4% (95% CI: 3–6), syndrome of inappropria te secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5–14), severe epist axis in 2% (95% CI: 0–4), and cerebrospinal fluid leak in 4% (95% CI: 2–6). Thirty-five (81 %) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. Conclusion: The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the hete rogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries.
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- 2022
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181. The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres
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Luca Persani, Martine Cools, Stamatina Ioakim, S Faisal Ahmed, Silvia Andonova, Magdalena Avbelj-Stefanija, Federico Baronio, Jerome Bouligand, Hennie T Bruggenwirth, Justin H Davies, Elfride De Baere, Iveta Dzivite-Krisane, Paula Fernandez-Alvarez, Alexander Gheldof, Claudia Giavoli, Claus H Gravholt, Olaf Hiort, Paul-Martin Holterhus, Anders Juul, Csilla Krausz, Kristina Lagerstedt-Robinson, Ruth McGowan, Uta Neumann, Antonio Novelli, Xavier Peyrassol, Leonidas A Phylactou, Julia Rohayem, Philippe Touraine, Dineke Westra, Valeria Vezzoli, and Raffaella Rossetti
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next-generation sequencing ,rare diseases or syndromes ,disorders of sex development ,congenital hypogonadotropic hypogonadism ,primary ovarian insufficiency ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11–490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.
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- 2022
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182. Integrating clinical and genetic approaches in the diagnosis of 46,XY disorders of sex development
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Zofia Kolesinska, James Acierno, S Faisal Ahmed, Cheng Xu, Karina Kapczuk, Anna Skorczyk-Werner, Hanna Mikos, Aleksandra Rojek, Andreas Massouras, Maciej R Krawczynski, Nelly Pitteloud, and Marek Niedziela
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array-comparative genomic hybridization ,differences and/or disorders of sex development ,massive parallel/next generation sequencing ,oligogenicity ,46 ,XY DSD ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
46,XY differences and/or disorders of sex development (DSD) are clinically and genetically heterogeneous conditions. Although complete androgen insensitivity syndrome has a strong genotype–phenotype correlation, the other types of 46,XY DSD are less well defined, and thus, the precise diagnosis is challenging. This study focused on comparing the relationship between clinical assessment and genetic findings in a cohort of well-phenotyped patients with 46,XY DSD. The study was an analysis of clinical investigations followed by genetic testing performed on 35 patients presenting to a single center. The clinical assessment included external masculinization score (EMS), endocrine profiling and radiological evaluation. Array-comparative genomic hybridization (array-CGH) and sequencing of DSD-related genes were performed. Using an integrated approach, reaching the definitive diagnosis was possible in 12 children. The correlation between clinical and genetic findings was higher in patients with a more severe phenotype (median EMS 2.5 vs 6; P = 0.04). However, in 13 children, at least one variant of uncertain significance was identified, and most times this variant did not correspond to the original clinical diagnosis. In three patients, the genetic studies guided further clinical assessment which resulted in a reclassification of initial clinical diagnosis. Furthermore, we identified eight patients harboring variants in more than one DSD genes, which was not seen in controls (2.5%; P = 0.0003). In summary, taking into account potential challenges in reaching the definitive diagnosis in 46,XY DSD, only integrated approach seems to be the best routine practice.
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- 2018
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183. Gonadal Function in Boys with Bilateral Undescended Testes.
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Lucas-Herald AK, Alkanhal KI, Caney E, Malik I, Alimussina M, McNeilly JD, Bradnock T, Lee B, Steven M, Flett M, O'Toole S, McGowan R, and Faisal Ahmed S
- Abstract
Background: Bilateral undescended testes (BUDT) may be a marker of an underlying condition that affects sex development or maturation., Aims: To describe the extent of gonadal dysfunction in cases of BUDT who had systematic endocrine and genetic evaluation at a single tertiary pediatric center., Methods: A retrospective review was conducted of all boys with BUDT who had endocrine evaluation between 2008 and 2021 at the Royal Hospital for Children, Glasgow (RHCG). Continuous variables were analyzed using Mann-Whitney U and non-continuous variables using Fisher's exact, via Graphpad Prism v 8.0. Multivariable logistic regression was used to identify any associations between groups. A P < .05 was considered statistically significant., Results: A total of 243 bilateral orchidopexies were performed at RHCG between 2008 and 2021. Of these 130 (53%) boys were seen by the endocrine team. The median (range) age at first orchidopexy was 1 year (0.2, 18.0) with 16 (12%) requiring re-do orchidopexy. The median External Masculinization Score of the group was 10 (2, 11) with 33 (25%) having additional genital features. Of the 130 boys, 71 (55%) had extragenital anomalies. Of the 70 who were tested, a genetic abnormality was detected in 38 (54%), most commonly a chromosomal variant in 16 (40%). Of the 100 who were tested, endocrine dysfunction was identified in 38 (38%)., Conclusion: Genetic findings and evidence of gonadal dysfunction are common in boys who are investigated secondary to presentation with BUDT. Endocrine and genetic evaluation should be part of routine clinical management of all cases of BUDT., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)
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- 2023
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184. Salivary androgens in adolescence and their value as a marker of puberty: results from the SCAMP cohort.
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Patjamontri S, Spiers A, Smith RB, Shen C, Adaway J, Keevil BG, Toledano MB, and Faisal Ahmed S
- Abstract
Context: Salivary androgens represent non-invasive biomarkers of puberty that may have utility in clinical and population studies., Objective: To understand normal age-related variation in salivary sex steroids and demonstrate their correlation to pubertal development in young adolescents., Design, Setting and Participants: School-based cohort study of 1495 adolescents at two time points for collecting saliva samples approximately 2 years apart., Outcome Measures: The saliva samples were analyzed for five androgens (testosterone, androstenedione (A4), 17-hydroxyprogesterone, 11-ketotestosterone and 11β-hydroxyandrostenedione) using liquid chromatography-mass spectrometry; in addition, salivary dehydroepiandrosterone (DHEA) and oestradiol (OE2) were analysed by ELISA. The pubertal staging was self-reported using the Pubertal Development Scale (PDS)., Results: In 1236 saliva samples from 903 boys aged between 11 and 16 years, salivary androgens except DHEA exhibited an increasing trend with an advancing age (ANOVA, P < 0.001), with salivary testosterone and A4 concentration showing the strongest correlation (r = 0.55, P < 0.001 and r = 0.48, P < 0.001, respectively). In a subgroup analysis of 155 and 63 saliva samples in boys and girls, respectively, morning salivary testosterone concentrations showed the highest correlation with composite PDS scores and voice-breaking category from PDS self-report in boys (r = 0.75, r = 0.67, respectively). In girls, salivary DHEA and OE2 had negligible correlations with age or composite PDS scores., Conclusion: In boys aged 11-16 years, an increase in salivary testosterone and A4 is associated with self-reported pubertal progress and represents valid non-invasive biomarkers of puberty in boys.
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- 2023
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185. Outcome of COVID-19 infections in patients with adrenal insufficiency and excess.
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Nowotny HF, Bryce J, Ali SR, Giordano R, Baronio F, Chifu I, Tschaidse L, Cools M, van den Akker EL, Falhammar H, Appelman-Dijkstra NM, Persani L, Beccuti G, Ross IL, Grozinsky-Glasberg S, Pereira AM, Husebye ES, Hahner S, Faisal Ahmed S, and Reisch N
- Abstract
Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce., Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing's syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021., Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison's disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission., Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules.
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- 2023
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186. Starting point for benchmarking outcomes and reporting of pituitary adenoma surgery within the European Reference Network on Rare Endocrine Conditions (Endo-ERN): results from a meta-analysis and survey study.
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Zamanipoor Najafabadi AH, van der Meulen M, Priego Zurita AL, Faisal Ahmed S, van Furth WR, Charmandari E, Hiort O, Pereira AM, Dattani M, Vitali D, de Graaf JP, and Biermasz NR
- Abstract
Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pituitary adenoma within Endo-ERN., Design and Methods: Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by reference centers on their current surgical practice., Results: A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6-represented countries published 48 articles. Remission rates were 50% (95% CI: 42-59) for patients with acromegaly, 68% (95% CI: 60-75) for Cushing's disease, and 53% (95% CI: 39-66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37-61%) of patients and visual improvement in 78% (95% CI: 68-87). Mortality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11-23), transient diabetes insipidus in 12% (95% CI: 6-21), permanent diabetes insipidus in 4% (95% CI: 3-6), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5-14), severe epistaxis in 2% (95% CI: 0-4), and cerebrospinal fluid leak in 4% (95% CI: 2-6). Thirty-five (81%) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon., Conclusion: The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the heterogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries.
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- 2022
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187. The genetic diagnosis of rare endocrine disorders of sex development and maturation: a survey among Endo-ERN centres.
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Persani L, Cools M, Ioakim S, Faisal Ahmed S, Andonova S, Avbelj-Stefanija M, Baronio F, Bouligand J, Bruggenwirth HT, Davies JH, De Baere E, Dzivite-Krisane I, Fernandez-Alvarez P, Gheldof A, Giavoli C, Gravholt CH, Hiort O, Holterhus PM, Juul A, Krausz C, Lagerstedt-Robinson K, McGowan R, Neumann U, Novelli A, Peyrassol X, Phylactou LA, Rohayem J, Touraine P, Westra D, Vezzoli V, and Rossetti R
- Abstract
Differences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries. All HCPs, except 1, performed NGS investigations for SDM disorders on 6720 patients, 3764 (56%) with differences of sex development (DSD), including 811 unexplained primary ovarian insufficiency, and 2956 (44%) with congenital hypogonadotropic hypogonadism (CHH). The approaches varied from targeted analysis of custom gene panels (range: 11-490 genes) in 81.5% of cases or whole exome sequencing with the extraction of a virtual panel in the remaining cases. These analyses were performed for diagnostic purposes in 21 HCPs, supported by the National Health Systems in 16 cases. The likelihood of finding a variant ranged between 7 and 60%, mainly depending upon the number of analysed genes or criteria used for reporting, most HCPs also reporting variants of uncertain significance. These data illustrate the status of genetic diagnosis of DSD and CHH across Europe. In most countries, these analyses are performed for diagnostic purposes, yielding highly variable results, thus suggesting the need for harmonization and general improvements of NGS approaches.
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- 2022
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188. Analysis of therapy monitoring in the International Congenital Adrenal Hyperplasia Registry.
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Lawrence N, Bacila I, Dawson J, Bryce J, Ali SR, van den Akker ELT, Bachega TASS, Baronio F, Birkebaek NH, Bonfig W, van der Grinten HC, Costa EC, de Vries L, Elsedfy H, Güven A, Hannema S, Iotova V, van der Kamp HJ, Clemente M, Lichiardopol CR, Milenkovic T, Neumann U, Nordenström A, Poyrazoğlu Ş, Probst-Scheidegger U, De Sanctis L, Tadokoro-Cuccaro R, Thankamony A, Vieites A, Yavaş Z, Faisal Ahmed S, and Krone N
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- 17-alpha-Hydroxyprogesterone, Androstenedione, Child, Child, Preschool, Female, Humans, Hydrocortisone therapeutic use, Male, Progesterone, Registries, Retrospective Studies, Adrenal Hyperplasia, Congenital drug therapy
- Abstract
Objective: Congenital adrenal hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4)., Design: Retrospective cohort study using real-world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries., Patients: Pseudonymized data from children with 21-hydroxylase deficiency (21OHD) recorded in the International CAH Registry., Measurements: Assessments between January 2000 and October 2020 in patients prescribed HC were reviewed to summarise biomarkers 17OHP and D4 and HC dose. Longitudinal assessment of measures was carried out using linear mixed-effects models (LMEM)., Results: Cohort of 345 patients, 52.2% female, median age 4.3 years (interquartile range: 3.1-9.2) were taking a median 11.3 mg/m
2 /day (8.6-14.4) of HC. Median 17OHP was 35.7 nmol/l (3.0-104.0). Median D4 under 12 years was 0 nmol/L (0-2.0) and above 12 years was 10.5 nmol/L (3.9-21.0). There were significant differences in biomarker values between centres (p < 0.05). Correlation between D4 and 17OHP was good in multiple regression with age (p < 0.001, R2 = 0.29). In longitudinal assessment, 17OHP levels did not change with age, whereas D4 levels increased with age (p < 0.001, R2 = 0.08). Neither biomarker varied directly with dose or weight (p > 0.05). Multivariate LMEM showed HC dose decreasing by 1.0 mg/m2 /day for every 1 point increase in weight standard deviation score., Discussion: Registry data show large variability in 17OHP and D4 between centres. 17OHP correlates with D4 well when accounting for age. Prescribed HC dose per body surface area decreased with weight gain., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)- Published
- 2022
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189. 3T-MRI-based age, sex and site-specific markers of musculoskeletal health in healthy children and young adults.
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Elsharkasi HM, Chen SC, Steell L, Joseph S, Abdalrahaman N, McComb C, Johnston B, Foster J, Wong SC, and Faisal Ahmed S
- Abstract
Objective: The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people., Design: Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.0, 30.0)., Methods: Detailed assessment of bone microarchitecture (constructive interference in the steady state (CISS) sequence, voxel size 0.2 × 0.2 × 0.4 mm3), bone geometry (T1-weighted turbo spin echo (TSE) sequence, voxel size 0.4 × 0.4 × 2 mm3) and bone marrow (1H-MRS, point resolved spectroscopy sequence (PRESS) (single voxel size 20 × 20 × 20 mm3) size and muscle adiposity (Dixon, voxel size 1.1 × 1.1 × 2 mm3)., Results: There was an inverse association of apparent bone volume/total volume (appBV/TV) with age (r = -0.5, P < 0.0005). Cortical area, endosteal and periosteal circumferences and muscle cross-sectional area showed a positive association to age (r > 0.49, P < 0.0001). In those over 17 years of age, these parameters were also higher in males than females (P < 0.05). This sex difference was also evident for appBV/TV and bone marrow adiposity (BMA) in the older participants (P < 0.05). AppBV/TV showed a negative correlation with BMA (r = -0.22, P = 0.01) which also showed an association with muscle adiposity (r = 0.24, P = 0.04). Cortical geometric parameters were highly correlated with muscle area (r > 0.57, P < 0.01)., Conclusions: In addition to providing deep insight into the normal relationships between bone, fat and muscle in young people, these novel data emphasize the role of MRI as a non-invasive method for performing a comprehensive and integrated assessment of musculoskeletal health in the growing skeleton.
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- 2022
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190. Congenital Micropenis: Etiology And Management.
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Stancampiano MR, Suzuki K, O'Toole S, Russo G, Yamada G, and Faisal Ahmed S
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In the newborn, penile length is determined by a number of androgen dependent and independent factors. The current literature suggests that there are interracial differences in stretched penile length in the newborn and although congenital micropenis should be defined as a stretched penile length of less than 2.5 SDS of the mean for the corresponding population and gestation, a pragmatic approach would be to evaluate all boys with a stretched penile length below 2 cm, as congenital micropenis can be a marker for a wide range of endocrine conditions. However, it remains unclear as to whether the state of micropenis, itself, is associated with any long-term consequences. There is a lack of systematic studies comparing the impact of different therapeutic options on long-term outcomes, in terms of genital appearance, quality of life, and sexual satisfaction. To date, research has been hampered by a small sample size and inclusion of a wide range of heterogeneous diagnoses; for these reasons, condition-specific outcomes have been difficult to compare between studies. Lastly, there is a need for a greater collaborative effort in collecting standardized data so that all real-world or experimental interventions performed at an early age can be studied systematically into adulthood., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)
- Published
- 2021
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191. A survey of the feasibility of developing osteoporosis clinical trials in Duchenne muscular dystrophy: Survey of the opinion of young people with Duchenne muscular dystrophy, families and clinicians.
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Choong Wong S, Joseph S, Capaldi N, Marco MD, Dunne J, Guglieri M, Horrocks I, Straub V, and Faisal Ahmed S
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- Adolescent, Feasibility Studies, Humans, Patient Participation, Placebos, Quality of Life, Surveys and Questionnaires, Clinical Trials as Topic, Muscular Dystrophy, Duchenne drug therapy, Osteoporosis drug therapy
- Abstract
Background/aims: Given the extent of osteoporosis in people with Duchenne muscular dystrophy treated with glucocorticoids and the limited evidence of bone-protective therapies, clinical trials are needed. We conducted surveys to obtain the opinion of young people with Duchenne muscular dystrophy, parents/guardians and neuromuscular clinicians on the feasibility of osteoporosis clinical trials in this population., Methods: Online surveys were sent to three groups: (a) people with a confirmed diagnosis of Duchenne muscular dystrophy (≥14 years), (b) parents and guardians and (c) neuromuscular clinicians in the UK NorthStar Clinical Network. Surveys (a) and (b) were distributed via the UK Duchenne muscular dystrophy Registry., Results: Survey respondents included 52 people with Duchenne muscular dystrophy with a median age of 17 years (range: 14, 40) and 183 parents/guardians. Fourteen out of 23 (61%) NorthStar centres responded. Of the 52 people with Duchenne muscular dystrophy, 13 (25%) were very concerned about their bone health and 21 (40%) were slightly concerned. Of the 183 parents/guardians, 75 (41%) were very concerned about their son's bone health and 90 (49%) were slightly concerned. Fractures and quality of life were the top two main outcome measures identified by people with Duchenne muscular dystrophy. Fractures and bone density were the top two main outcome measures identified by parents/guardians and neuromuscular clinicians. Thirty percent of people with Duchenne muscular dystrophy and 40% of parents/guardians would not take part if an osteoporosis trial involved a placebo that was administered parenterally. Only 2 of the 14 NorthStar centres (14%) would enrol people with Duchenne muscular dystrophy if a parenteral placebo was used in an osteoporosis trial in Duchenne muscular dystrophy., Conclusion: There is great awareness of bone health and the need for bone-protective trials among people with Duchenne muscular dystrophy and their carers. However, a proportion of people with Duchenne muscular dystrophy and parents are reluctant to participate in a placebo-controlled osteoporosis trial that included a parenteral therapy. A larger proportion of health care experts are unwilling to enrol their patients in such a trial. Our finding is relevant for the design of bone-protective studies in Duchenne muscular dystrophy.
- Published
- 2021
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192. Plasma Renin Measurements are Unrelated to Mineralocorticoid Replacement Dose in Patients With Primary Adrenal Insufficiency.
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Pofi R, Prete A, Thornton-Jones V, Bryce J, Ali SR, Faisal Ahmed S, Balsamo A, Baronio F, Cannuccia A, Guven A, Guran T, Darendeliler F, Higham C, Bonfig W, de Vries L, Bachega TASS, Miranda MC, Mendonca BB, Iotova V, Korbonits M, Krone NP, Krone R, Lenzi A, Arlt W, Ross RJ, Isidori AM, and Tomlinson JW
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Dose-Response Relationship, Drug, Female, Hormone Replacement Therapy methods, Humans, Infant, Infant, Newborn, Longitudinal Studies, Male, Middle Aged, Mineralocorticoids pharmacology, Renin drug effects, Retrospective Studies, Young Adult, Adrenal Insufficiency blood, Adrenal Insufficiency drug therapy, Mineralocorticoids administration & dosage, Renin blood
- Abstract
Context: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency., Objective: To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency., Design: Observational, retrospective, longitudinal analysis., Patients: A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison disease (AD) were analysed., Main Outcome Measures: PRC, electrolytes, blood pressure (BP), and anthropometric parameters were used to predict their utility in optimizing MC replacement dose., Results: PRC was low, normal, or high in 19%, 36%, and 44% of patients, respectively, with wide variability in MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC., Conclusions: The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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193. Understanding the needs of professionals who provide psychosocial care for children and adults with disorders of sex development.
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Dessens A, Guaragna-Filho G, Kyriakou A, Bryce J, Sanders C, Nordenskjöld A, Rozas M, Iotova V, Ediati A, Juul A, Krawczynski M, Hiort O, and Faisal Ahmed S
- Abstract
Objective: Disorders in sex development (DSD) can be treated well medically, but families will encounter many psychosocial challenges. Promoting counselling to facilitate acceptance and coping is important yet equality of access is unknown. This study investigated the modalities of psychosocial care provided in centres of DSD care., Methods: An international survey conducted among 93 providers of psychosocial care, identified through clinical networks, registries and professional forums., Results: Forty-six respondents from 22 different countries filled out the survey (49%). Most respondents (78%) were based in hospital-based expert teams. Referrals came from paediatric endocrinologists (76%), gynaecologists (39%) and paediatric urologists (37%). Psychological counselling was most frequently given to parents (74%), followed by children (39%), adolescents (37%) and adults (11%) and was most frequently focused on coping and acceptance of DSD (54%), education (52%), the atypical body (39%) and genital (41%), decisions on genital surgery (33%), complications with sexual intercourse (29%), disclosure (28%) and acceptance of infertility (11%). Respondents most frequently observed DSD related confusion about gender (54%), acceptance of cross gender behaviour (50%), anxiety (43%) and sadness and depression (38%)., Conclusions: Most psychosocial care is provided to parents. It is assumed that parental support is important as acceptance is conditional to become affectionate caretakers. Although it may be more difficult for youngsters to communicate about their condition and treatment, providing opportunity to bring up issues that are important for them, is imperative. Clinicians and parents should be aware that parental and patients' interests may not correspond completely. Psychosocial management should also include transition and adult care., Competing Interests: Competing interests: None declared.
- Published
- 2017
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194. A critical appraisal of vertebral fracture assessment in paediatrics.
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Kyriakou A, Shepherd S, Mason A, and Faisal Ahmed S
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- Absorptiometry, Photon methods, Adolescent, Child, Child, Preschool, Cohort Studies, Female, Humans, Male, Pediatrics methods, Absorptiometry, Photon standards, Pediatrics standards, Spinal Fractures diagnostic imaging
- Abstract
Purpose: There is a need to improve our understanding of the clinical utility of vertebral fracture assessment (VFA) in paediatrics and this requires a thorough evaluation of its readability, reproducibility, and accuracy for identifying VF., Methods: VFA was performed independently by two observers, in 165 children and adolescents with a median age of 13.4 years (range, 3.6, 18). In 20 of these subjects, VFA was compared to lateral vertebral morphometry assessment on lateral spine X-ray (LVM)., Results: 1528 (84%) of the vertebrae were adequately visualised by both observers for VFA. Interobserver agreement in vertebral readability was 94% (kappa, 0.73 [95% CI, 0.68, 0.73]). 93% of the non-readable vertebrae were located between T6 and T9. Interobserver agreement per-vertebra for the presence of VF was 99% (kappa, 0.85 [95% CI, 0.79, 0.91]). Interobserver agreement per-subject was 91% (kappa, 0.78 [95% CI, 0.66, 0.87]). Per-vertebra agreement between LVM and VFA was 95% (kappa 0.79 [95% CI, 0.62, 0.92]) and per-subject agreement was 95% (kappa, 0.88 [95% CI, 0.58, 1.0]). Accepting LVM as the gold standard, VFA had a positive predictive value (PPV) of 90% and a negative predictive value (NPV) of 95% in per-vertebra analysis and a PPV of 100% and NPV of 93% in per-subject analysis., Conclusion: VFA reaches an excellent level of agreement between observers and a high level of accuracy in identifying VF in a paediatric population. The readability of vertebrae at the mid thoracic region is suboptimal and interpretation at this level should be exercised with caution., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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195. E-consultation for DSD: a global platform for access to expert advice.
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Drop SL, Mure PY, Wood D, El-Ghoneimi A, and Faisal Ahmed S
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- Child, Female, Humans, Male, Pediatric Assistants, Consultants, Disorders of Sex Development diagnosis, Disorders of Sex Development therapy, Global Health, Telemedicine
- Abstract
Electronic consultation (e-consultation) has been used for some years to facilitate communication between patients and their doctors, but it is also emerging as a valuable tool aiding communication between clinicians, both primary care and specialists, about a patient's care. Telehealth systems are being developed to provide video consultations to support diagnosis and management, as well as supporting clinical networks and health professional education. In some world regions, it seems increasingly likely that most rare diseases will be managed through a network of centres of expertise, and e-consultation systems may become a vital component of the service provided by these networks. Long-distance consultation across geographical and national boundaries has been used between colleagues in DSD for many years. However, the development of a robust and secure e-consultation service within the international DSD community appears to be timely. It will extend the current database and e-learning facilities, and should be achieved with the objective of providing expert opinion on a worldwide basis. It is proposed to install a steering committee to oversee the various practical, legal and cultural issues setting standards on data collection and exchange. The opportunity to broaden access to healthcare for all DSD patients and to widen discussion across the DSD community is valuable, and it is the view of the authors that this should be pursued and developed., (Copyright © 2012 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2012
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196. SOCS2 is the critical regulator of GH action in murine growth plate chondrogenesis.
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Pass C, MacRae VE, Huesa C, Faisal Ahmed S, and Farquharson C
- Subjects
- Animals, Blotting, Western, Cell Proliferation, Cells, Cultured, Chondrocytes drug effects, Chondrocytes metabolism, Gene Expression Regulation, Developmental, Growth Hormone pharmacology, Growth Plate cytology, Immunohistochemistry, Insulin-Like Growth Factor I metabolism, Male, Metatarsal Bones cytology, Metatarsal Bones drug effects, Metatarsal Bones growth & development, Mice, Mice, Knockout, Phosphorylation, Polymerase Chain Reaction, STAT Transcription Factors metabolism, Signal Transduction, Suppressor of Cytokine Signaling Proteins genetics, Chondrocytes cytology, Chondrogenesis, Genotype, Growth Hormone metabolism, Growth Plate metabolism, Suppressor of Cytokine Signaling Proteins metabolism
- Abstract
Suppressor of Cytokine Signaling-2 (SOCS2) is a negative regulator of growth hormone (GH) signaling and bone growth via inhibition of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. This has been classically demonstrated by the overgrowth phenotype of SOCS2(-/-) mice, which has normal systemic insulin-like growth factor 1 (IGF-1) levels. The local effects of GH on bone growth are equivocal, and therefore this study aimed to understand better the SOCS2 signaling mechanisms mediating the local actions of GH on epiphyseal chondrocytes and bone growth. SOCS2, in contrast to SOCS1 and SOCS3 expression, was increased in cultured chondrocytes after GH challenge. Gain- and loss-of-function studies indicated that GH-stimulated chondrocyte STATs-1, -3, and -5 phosphorylation was increased in SOCS2(-/-) chondrocytes but not in cells overexpressing SOCS2. This increased chondrocyte STAT signaling in the absence of SOCS2 is likely to explain the observed GH stimulation of longitudinal growth of cultured SOCS2(-/-) embryonic metatarsals and the proliferation of chondrocytes within. Consistent with this metatarsal data, bone growth rates, growth plate widths, and chondrocyte proliferation were all increased in SOCS2(-/-) 6-week-old mice as was the number of phosphorylated STAT-5-positive hypertrophic chondrocytes. The SOCS2(-/-) mouse represents a valid model for studying the local effects of GH on bone growth., (Copyright © 2012 American Society for Bone and Mineral Research.)
- Published
- 2012
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197. Balanced translocation of 10q and13q, including the PTEN gene, in a boy with a human chorionic gonadotropin-secreting tumor and the Bannayan-Riley-Ruvalcaba syndrome.
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Faisal Ahmed S, Marsh DJ, Weremowicz S, Morton CC, Williams DM, and Eng C
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Diabetes Insipidus genetics, Head anatomy & histology, Humans, Magnetic Resonance Imaging, Male, PTEN Phosphohydrolase, Pituitary Neoplasms genetics, Pituitary Neoplasms therapy, Puberty, Precocious genetics, Radiotherapy, Syndrome, Chorionic Gonadotropin metabolism, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 13, Phosphoric Monoester Hydrolases genetics, Pituitary Neoplasms metabolism, Translocation, Genetic, Tumor Suppressor Proteins
- Published
- 1999
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198. Sexual dimorphism in the neonatal gonad.
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Hughes IA, Coleman N, Faisal Ahmed S, Ng KL, Cheng A, Lim HN, and Hawkins JR
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- Embryonic and Fetal Development genetics, Embryonic and Fetal Development physiology, Endocrine System growth & development, Female, Humans, Infant, Newborn, Male, Ovary pathology, Sex Characteristics, Testis pathology, Endocrine System physiology, Ovary growth & development, Sex Determination Processes, Testis growth & development, Y Chromosome
- Abstract
The neonatal gonad has two distinct forms (i.e., is sexually dimorphic), as judged by morphological and endocrine characteristics. The dimorphic process begins early in embryogenesis. It is well established by the time of birth, by which time the genital ridge has developed into either a testis or an ovary. The mechanisms involved in sex determination involve the Y chromosome, autosomal genes, transcription factors and possibly other unidentified control networks. This review paper describes the morphological changes that occur and the endocrine functions in the developing gonads. It highlights a number of important differences in fetal and neonatal gonadal function. The testis has early histological definition, several determining genes, delayed germ cell maturation, early autonomous steroid secretion, luteinizing hormone (LH) receptor and steroid enzyme expression, high fetal testicular testosterone content, prominent postnatal Leydig and Sertoli cells and high postnatal serum testosterone levels. The ovary has a prolonged monomorphic state, probably one determining gene, germ cells in early meiotic arrest, delayed expression of LH receptor and aromatase, low ovarian oestradiol content, prominent postnatal follicles and low postnatal serum oestradiol levels.
- Published
- 1999
- Full Text
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