Endocrine Abstracts

Background: Our practice is to commence newly diagnosed children and young people (CYP) with diabetes, over 5 years old, on multiple daily insulin (MDI), using fixed Insulin to Carbohydrate ratios (ICRs) with meals across the day. ICRs are subsequently adjusted according to blood glucose response, individualising insulin treatment. We know intensified insulin therapy includes use of varied ICRs, reflecting varying insulin sensitivity at different times of day. We do not know w...

Zebrafish has emerged as an important vertebrate in vivo model to study human disease. Steroidogenesis in zebrafish is not well characterised. Human CYP11A1 (hCYP11A1) catalyses the first step of steroidogenesis, the conversion of cholesterol to pregnenolone. Zebrafish Cyp11a1 (zCyp11a1) is essential during embryogenesis. Published data suggest that zCyp11a1 facilitates steroidogenesis in the interrenal (equivalent to mammalian adrenal), gonad and brain. We identified...

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individuals, with nor...

Aim: To describe the prevalence and natural history of retinopathy in a cohort of children and young people with type 1 diabetes attending a tertiary hospital diabetes clinic.Methods: We analysed follow-up data from 2008 to 2010 on all children eligible for retinopathy screening using the ‘Twinkle’ diabetes database and the regional retinal screening database.Results: 88% (149/169) of eligible children were screened in 20...

Congenital adrenal hyperplasia due to P450 oxidoreductase (POR) deficiency (ORD) results in disordered sex development (DSD) in individuals of both sexes. POR provides electrons to CYP17A1 thereby facilitating synthesis of the major androgen precursor dehydroepiandrosterone (DHEA). ORD disrupts this enzymatic step, resulting in deficient synthesis of 5α-dihydrotestosterone (DHT) via DHEA, readily explaining undervirilisation (46,XY DSD) in male ORD neonates. Female virili...

Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis, facilitating conversion of cholesterol to pregnenolone. Cholesterol, transported by steroidogenic acute regulatory protein (StAR) into the inner mitochondrial membrane, is converted by CYP11A1 into 22R-hydroxycholesterol. Subsequently, CYP11A1 converts 22R-hydroxycholesterol by 20alpha-hydroxylation and cleavage of the C20–C22 bond into pregnenolone. All pat...

CYP17A1 is a key enzyme of human steroidogenesis, which is unique in that it catalyses two reactions, 17-hydroxylase activity converting pregnenolone and progesterone to 17-hydroxypregnenolone (17Preg) and 17-hydroxy-progesterone, respectively, and 17,20 lyase activity, responsible for the conversion of 17Preg to dehydroepiandrosterone the crucial precursor of human sex steroid biosynthesis. 17-hydroxylase deficiency, a variant of congenital adrenal hyperplasia, results in glu...

Background: Incorporating the ideas and views of children and young people (CYP) with endocrine conditions from early stages in the research life cycle will increase the benefit for patients and contribute to high impact research.Methods: We conducted two days of patient and public involvement (PPI) sessions with patients from a tertiary endocrine centre who are living with Congenital Adrenal Hypoplasia (CAH). We explore...

Background: As diagnostic workup and management of patients with Disorders of Sex Development (DSD) evolves, access to the latest advances should continue.Aims: To explore whether DSD patients in the West Midlands Region (WMR) remain under follow up, having optimal diagnostic workup and management.Method: An unselected cohort of 48 patients with discrepant phenotypic gender and sex chromosomes in the WMR were identified from the re...

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...