Endocrine Abstracts

A 19-year-old student was referred with a history of increasing anxiety attacks, palpitations and breathlessness. Blood pressure and urinary catecholamine levels were elevated. MRI imaging confirmed a para-aortic paraganglionoma and MIBG scan highlighted bony metastases. The patient underwent surgery for the primary lesion and targeted MIBG therapy for metastases.Age of onset, malignant disease and metastases increase the likelihood of a genetic cause an...

In response to the 2003 Government White Paper entitled ‘Our future, Our inheritance’, we piloted a project to promote the genetic service within tertiary medicine. Three clinical nurse specialists (CNS); renal, cardiac and endocrine, are the catalyst for interaction between disciplines. This abstract relates the endocrine genetic experience.Targeting patients and families with genetic endocrine disease is achieved by three methods; identificat...

Introduction: Rare genetic overgrowth disorders are a group of conditions characterised by height and/or head circumference >2 S.D. above the mean for age and sex, learning disability, congenital anomalies, and in some cases childhood tumours. POD is a national cohort study that includes a next generation sequencing (NGS) panel of overgrowth genes. We present a new model for clinical confirmation of pathogenic variants identified by this research panel. Clin...

Background: Congenital adrenal hyperplasia (CAH) is the underlying diagnosis in most newborns presenting with 46,XX disorders of sex development (DSD). Cytochrome P450 oxidoreductase deficiency (PORD) is a rare form of CAH caused by inactivating mutations in the POR gene. The hallmark feature of PORD is combined sex-steroid and glucocorticoid deficiency due to impairment of CYP17A1 and CYP21A2. Skeletal malformations resembling the Antley-Bixler Syndrome phenotype are common i...

Disorders of sex development (DSDs) refer to a range of congenital disorders where the chromosomal, gonadal or anatomical sex is atypical. Patients typically present in the newborn period where ambiguous genitalia often prevents immediate gender assignment or during the adolescent period where atypical sexual development becomes apparent. Genetic testing is key in establishing the diagnosis allowing for personalised management of these patients, and can significantly reduce th...

Introduction: Steroid 5-α reductase type 2 deficiency causes 46,XY disorder of sex development (DSD) and is an autosomal recessive disorder resulting from mutations in the SRD5A2 gene. SRD5A2 facilitates the conversion of testosterone to dihydrotestosterone (DHT), crucially required for masculinisation of external genitalia. Thus 46,XY individuals with SRD5A2 mutations present with varying severity of undermasculinisation.We descri...

Introduction: Osteogenesis imperfecta (OI) is a genetic, heterogeneous, connective tissue disorder most commonly caused by mutations in type I collagen genes. A hallmark of disease is frequent fractures that are precipitated by minimal trauma. There are limited data on the impact of OI on non-skeletal outcomes across the lifecourse. We present cross-sectional data of one of the largest single centre patient cohorts of OI in adulthood (n=186).The aim of this study was ...

Background: 3-M syndrome is associated with severe proportionate pre- and postnatal growth restriction, and is caused by mutations in CUL7, OBSL1, or CCDC8 genes.Aims and methods: To define baseline growth and GH–IGF1 axis status as well as response to r-hGH in relation to mutation status in 3-M children, using retrospective analysis of data from clinical notes.Results: 50 individuals (19 CUL7, 19 <...

Background: Congenital, isolated, central, hypothyroidism (CCH), is rare and evades diagnosis on TSH-based congenital hypothyroidism screening programmes in the UK. Genetic ascertainment is therefore paramount in enabling prompt diagnosis and treatment of familial cases. Recognised causes include TSHB and IGSF1 gene defects, with only two previous reports of biallelic, highly disruptive (nonsense; R17X, in-frame deletion and missense; p.S115-T117del+T118), mu...

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...