A5006439423- Sexual Differentiation and Disorders
- Hormonal and reproductive studies
- Adrenal Hormones and Disorders
- Hormonal Regulation and Hypertension
- Metabolism and Genetic Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Growth Hormone and Insulin-like Growth Factors
- Urological Disorders and Treatments
- Birth, Development, and Health
- Diet and metabolism studies
- Reproductive biology and impacts on aquatic species
- Stress Responses and Cortisol
- Zebrafish Biomedical Research Applications
- Adrenal and Paraganglionic Tumors
- Diabetes Management and Research
- Pituitary Gland Disorders and Treatments
- Physiological and biochemical adaptations
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Diabetes and associated disorders
- Ion Transport and Channel Regulation
- Pharmacogenetics and Drug Metabolism
- Urologic and reproductive health conditions
- Estrogen and related hormone effects
- Prostate Cancer Treatment and Research
University of Sheffield
2016-2025
Sheffield Children's Hospital
2016-2025
Sheffield Children's NHS Foundation Trust
2018-2025
University Hospital Carl Gustav Carus
2019-2023
Technische Universität Dresden
2019-2023
Seoul National University Children's Hospital
2021
Radboud University Nijmegen
2021
Pfizer (United Kingdom)
2021
Novo Nordisk (United Kingdom)
2021
University of Birmingham
2010-2020
No consensus exists for management of adults with congenital adrenal hyperplasia (CAH) due to a paucity data from cohorts meaningful size.Our objective was establish the health status CAH.We conducted prospective cross-sectional study CAH attending specialized endocrine centers across United Kingdom.Participants included 203 patients (199 21-hydroxylase deficiency): 138 women, 65 men, median age 34 (range 18-69) years.Anthropometric, metabolic, and subjective evaluated. Anthropometric...
Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2-11% incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents diagnostic challenge patients with incidentalomas, tumor size, imaging, and even histology all providing unsatisfactory predictive values.Here we developed novel steroid metabolomic approach, mass spectrometry-based profiling followed by machine learning...
Abstract Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders. CAH most often caused by deficiency steroid 21-hydroxylase. The frequency CYP21-inactivating mutations and the genotype-phenotype relationship were characterized in 155 well defined unrelated patients. We able to elucidate 306 310 disease-causing alleles (diagnostic sensitivity, 98.7%). frequent mutation was intron 2 splice site (30.3%), followed gene deletions (20.3%), I172N (19.7%) large conversions...
Summary It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) assessed by an experienced clinician adequate knowledge about the range conditions associated DSD. If there doubt, case should be discussed regional team. In most cases, particularly in newborn, paediatric endocrinologist within DSD team acts as first point contact. The underlying pathophysiology and strengths weaknesses tests can performed parents affected young person undertaken timely...
Dehydroepiandrosterone (DHEA) sulfotransferase, known as SULT2A1, converts the androgen precursor DHEA to its inactive sulfate ester, DHEAS [corrected], thereby preventing conversion of an active androgen. SULT2A1 requires 3'-phosphoadenosine-5'-phosphosulfate (PAPS) for catalytic activity. We have identified compound heterozygous mutations in gene encoding human PAPS synthase 2 (PAPSS2) a girl with premature pubarche, hyperandrogenic anovulation, very low levels, and increased levels. In...
Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, likely succumb hypoglycemia and/or overwhelming infection. Mutations receptor (MC2R) and melanocortin 2 accessory protein (MRAP), FGD types 1 respectively, account for approximately 45% cases.A locus chromosome 8 has previously been linked disease three families, but no underlying gene...
P450 oxidoreductase deficiency (PORD) is a unique congenital adrenal hyperplasia variant that manifests with glucocorticoid deficiency, disordered sex development (DSD), and skeletal malformations. No comprehensive data on genotype-phenotype correlations in Caucasian patients are available.The objective of the study was to establish large PORD cohort.The design clinical, biochemical, genetic assessment including multiplex ligation-dependent probe amplification (MLPA) 30 from 11 countries.We...
The focus of care in disorders sex development (DSD) is often directed to issues related and gender development. In addition, the molecular etiology remains unclear majority cases. To report range associated conditions identified international DSD (I-DSD) Registry. Anonymized data were extracted from I-DSD Registry for diagnosis, karyotype, rearing, genetic investigations, anomalies. If necessary, clarification was sought reporting clinician. Of 649 accessible cases, occurred 168 (26%); 103...
It is unclear whether the proportion of infants with a disorder sex development who are raised as male or female has changed over time. The temporal trends in assignment affected cases entered International Disorder Sex Development (I-DSD) Registry were studied.Cases disorders reported partial androgen insensitivity syndrome (PAIS; n = 118), gonadal (DGD; 232), and synthesis (DAS; 104) divided into those born before 1990, 1990-1999, after 1999. External appearance genitalia was described by...
Significance The currently used treatment regimen for the cancers of adrenal cortex involves mitotane, a nonspecific derivative pesticide DDT (1,1-(dichlorobiphenyl)-2,2-dichloroethane), which has an unclear mechanism action. Our studies in cell culture and genetic analysis public databases demonstrate that human adrenocortical carcinomas (ACCs) are remarkably sensitive to recently defined death pathway referred as ferroptosis, indicating induction ferroptosis could be promising approach...
Fertility rates in women with congenital adrenal hyperplasia (CAH) are reported to be poor, but few data available. We assessed and course of pregnancy, mode delivery long-term outcome offspring from CAH.A large cohort CAH due 21-hydroxylase deficiency had initially been diagnosed followed at one centre. Those who given birth were contacted. Information was gathered hospital records, direct patient contact, structured questionnaire the Documentation Pregnancy Preventive Care Booklets.Between...
Steroid 11beta-hydroxylase (CYP11B1) deficiency (11OHD) is the second most common form of congenital adrenal hyperplasia (CAH). Cases nonclassic 11OHD are rare compared with incidence 21-hydroxylase deficiency.The aim study was to analyze functional consequences seven novel CYP11B1 mutations (p.M88I, p.W116G, p.P159L, p.A165D, p.K254_A259del, p.R366C, p.T401A) found in three patients classic 11OHD, two and heterozygous carriers for mutations.We conducted studies employing a COS7 cell vitro...
Abstract Context: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data adults are lacking. Objective: The objective of the study was test whether severity disease-causing CYP21A2 mutations influences treatment and health status with CAH. Research Design Methods: We analyzed genotype 153 CAH from United Kingdom Congenital Hyperplasia Adult Study Executive cohort. Results: were distributed...