Endocrine Abstracts

Introduction: The UK 100,000 Genomes Project (100KGP) investigated the genetic basis of rare disease. The molecular drivers of most paediatric pituitary disease remains unknown.Methods: Children with genetically unexplained pituitary disorders attending a tertiary paediatric endocrinology centre were recruited to the 100KGP and underwent whole genome sequencing. Parental DNA was obtained where feasible. Virtual gene panels were applied and bioinformatic ...

Introduction: Coffin-Siris Syndrome (CSS) is a rare multisystem genetic disorder which often arises from genetic abnormalities within genes encoding for the SWI/SNF complex (ARID1A, ARID1B, DPF2, SMARCA4, SMARCB1, SMARCA2, SMARCE1). Endocrine abnormalities previously associated with this disorder include idiopathic short stature, hyperinsulinism, obesity, growth hormone deficiency, and cryptorchidism. We describe the endocrine features and associated radiological find...

Silver-Russell syndrome (SRS) is characterised by low birth weight, short stature, and feeding difficulties in childhood, with marked leanness also described. There is limited information on body composition in older people with SRS.Objective: To evaluate body composition in adults with SRS. Methods: Participants aged ≥18 years with molecularly-confirmed SRS attended a single study appointment. Body composition was evaluated ...

The classical features of Silver-Russell syndrome (SRS) appear to become less pronounced with increasing age. Small-for-gestational-age (SGA) birth is associated with adult metabolic syndrome. SRS is associated with SGA but the adult sequelae and long-term effects of childhood growth hormone (GH) treatment are unclear.Objective: To determine the phenotype and cardio-metabolic profile in older individuals with SRS and compare individuals previously untrea...

Childhood short stature in Silver-Russell syndrome (SRS) is frequently treated with growth hormone (GH), however final height and long-term body mass index (BMI) data are limited.Objective: To assess height and BMI in older individuals with molecularly confirmed SRS and compare those previously treated with GH to those untreated.Methods: Growth data on individuals aged ≥13 years with SRS were evaluated from UK, French and Ger...

Objectives: THRA mutations cause Resistance to Thyroid Hormone α (RTHα), an underdiagnosed disorder with hypothyroid features but near-normal thyroid function tests (TFTs). We developed a pathway, combining molecular analyses, new biomarkers and physiological measurements, to better diagnose and treat this disorder.Methods: Structural and functional analyses of THRA variants, discovered by next generation sequencing in specifi...