Endocrine Abstracts

Background/hypothesis: Congenital hyperinsulinism in infancy (CHI) mainly arises from mutations in ATP-sensitive potassium channel genes. However, the expression pattern of defects can be markedly diverse. In diffuse CHI (CHI-D) all islet cells express gene defects, whereas patients with focal CHI (CHI-F) only express defects in a localised region of islet cells due to loss of a maternally-imprinted locus. Here, we examined the properties of a novel population of CHI islet cel...

The Endocrine Society guidelines recommend initial testing for Cushing’s syndrome (CS) can be based on non-invasive late-night salivary cortisol measurement (NSC). In the BHSCT NSC (11pm), measured using the IBL ELISA kit has been found to be highly discriminative in identifying patients with CS. However it is a labour intensive test and the need for analysing samples in batches delays turnaround time, limiting its use in the routine work-up for CS. Roche provide an autom...

Introduction: Heavy menstrual bleeding (HMB) affects over 1 million women in the UK. At menses, progesterone (P4) withdrawal drives inflammation, tissue break-down and repair of the endometrium. Glucocorticoids are mediators of inflammation and angiogenesis. Our previous studies have demonstrated that differential endometrial expression of the glucocorticoid-metabolising enzymes, 11β-HSD-1 and -2, may play a role in HMB. We hypothesise that aberrant lo...

Introduction: Adverse neurodevelopmental outcomes have been recognised in children with hypoglycaemia due to early and late presenting congenital hyperinsulinism (CHI). The Vineland Adaptive Behaviour Scales II (VABS-II) is a standardised measure used to assess parent reported adaptive behaviour. The test measures five domains; motor, communication, daily living skills (DLS), socialisation, and maladaptive behaviour. We have used VABS-II to identify specific neurodevelopmental...

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...

Mammalian genes display pulsatile transcription dynamics with bursts of expression occurring with variable duration and frequency. Using the human prolactin gene as a model of tissue specific gene regulation, we have characterised the transcription dynamics of this gene in cell lines, primary cells and pituitary tissue slices. Our data indicate that the tissue environment may have an important influence on cellular transcription activity. Cultures of cells from enzymatically d...

Introduction: Congenital hyperinsulinism (CHI) is an important cause of hypoglycaemia in infancy requiring intensive medical and surgical support. Carbohydrate requirement (CHO) represents a simple index of severity but does not predict the failure of medical treatment and hence the requirement for pancreatectomy.Aims: To design and validate a severity tool for use in early onset CHI patients.Methods: To design the Manchester CHI s...

Fetal events can affect adult testosterone levels but how this occurs is unknown, as adult Leydig cells (ALC) do not differentiate until puberty. Qin et al. 2008 (PLos ONE) identified that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) is essential postnatally for ALC development. We hypothesized that: i) COUP-TFII+ non-Leydig interstitial cells are progenitors for ALC and are present in the fetal testis, ii) these ‘pr...

Background: Calculation of a urinary steroid metabolite ratio (uSMR) may be a useful method of improving diagnostic yield when investigating disorders of steroid hormone synthesis.Objective & HypothesisTo investigate the range of uSMR in children with suspected disorders of steroid hormone synthesis.Population / MethodsTen ratios were calculated on steroid metabolite data analysed b...

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoids thus amplifying their intracellular actions. 11β-HSD1 deficiency or inhibition, which improve metabolic syndrome and attenuate atherosclerosis in vulnerable rodent strains, is a target for drug development. However, 11β-HSD1 also converts 7-ketocholesterol (7KC) (which accumulates in fatty tissues), to the potentially more atherogenic, 7β-hydroxycholesterol. Whether a...