Endocrine Abstracts

Background: Childhood growth monitoring aims to identify growth failure and detect underlying pathology. According to UK guidance, height <-2.7 standard deviation score (SDS) (<0.4th percentile) is used as the referral threshold. Additional referral criteria include height deficit (HSDS-target height SDS) <-2.0 and height velocity (HV) SDS <-1.3. Lack of routine HV and mid-parental height calculation, combined with stricter cut-offs compared to other European c...

Background: GH resistance or primary IGF1 deficiency (PIGFD) presents with growth failure, low serum IGF1 and normal/elevated serum GH. PIGFD comprises a spectrum of phenotypic and biochemical abnormalities for which genetic GH–IGF1 axis defects may be causative.Objective: Genotyping of PIGFD patients referred for sequencing of candidate genes.Methods: From 2008 to 2013, 62 patients (42 males and 20 females), median age 6.9 ye...

Background: GH insensitivity (GHI) presents with growth failure, IGF-1 deficiency and normal/elevated GH (basal >5 μg/l and/or peak >10 μg/l). GHI encompasses a spectrum of clinical and biochemical abnormalities. Associations between phenotypic characteristics and genetic defects remain obscure.Objective: Identify phenotypic predictors of underlying genetic defects in GHI.Methods: In total of 102 children (62M) me...

Background: In children, Cushing’s disease (CD) presents with a combination of weight gain and slowed linear growth. First-line pituitary surgery is the treatment of choice for most patients. In paediatric patients, the transsphenoidal surgical success rate is 60%–98% when performed by an expert pituitary surgeon. There is a need for additional pharmacological interventions to control hypercortisolaemia, which are currently limited, in children and adolescents. In ph...

Background: Endogenous Cushing’s syndrome (CS) in children remains a challenge to diagnose and exclude. 24-h urinary free cortisol (UFC) measurements are a convenient, non-invasive test for paediatric patients.Objective: To assess the screening accuracy of 24-h UFC measurements in paediatric patients referred to our centre for evaluation of possible CS.Methods: A retrospective review of children referred to our centre between ...

Selective transsphenoidal adenomectomy remains the accepted first line treatment for Cushing’s disease (CD), until recently by microscopic (sublabial) transsphenoidal pituitary surgery. Endonasal transsphenoidal endoscopic surgery is emerging as a novel, less invasive treatment for pituitary adenomas with lower postoperative complications and morbidity. The safety of endoscopic surgery has been extensively reviewed in adult patients and is now considered best practice for...

Objectives: Noonan Syndrome (NS) is an autosomal dominant multi-system disorder characterised by short stature (SS), distinctive facial features and cardiovascular abnormalities. Mutations in multiple genes regulating the RAS-MAPK pathway have been identified in NS including 5 recently described novel LZTR1 variants. We identified 2 novel LZTR1 variants in patients with features of growth hormone insensitivity and NS. The molecular function of LZTR1 ...

Background: The low dose dexamethasone suppression test (LDDST) is an important investigation for suspected Cushing’s syndrome (CS). The traditional definition of normal suppression of serum cortisol to ≤50 nmol/l (0.5 mg 6 hrly × 48 hrs) comes from a time when biochemical auto analysers did not routinely detect very low values. Previous studies reported 5.1–8.3% of patients with Cushing’s disease (CD) suppressed to <50 nmol/l at 48 hrs. Many clin...

Objectives: The homozygous GHR pseudoexon (6Ψ) mutation leads to aberrant splicing of the GHR gene with clinical and biochemical heterogeneity. We investigated whether the phenotypic variability could be explained by transcript heterogeneity i.e. ratio of abnormal (6Ψ GHR) to normal (WT GHR) transcripts and/or the presence of concurrent defects in other short stature (SS) genes.Methods: 6 Ψ GHR ...

Context: Severe or ‘classical’ growth hormone insensitivity (GHI) is characterised by extreme short stature, dysmorphism and metabolic anomalies. It is caused by homozygous or compound heterozygous mutations of the Growth Hormone Receptor gene (GHR). Genetic analysis traditionally focuses on the exonic regions of gene(s). The non-coding regions of the genome may harbour numerous disease-causing mutations that are not well recognised or understood.<p clas...