Endocrine Abstracts

Background: Quality of life (QoL) has been variously reported as normal or impaired in congenital adrenal hyperplasia (CAH) adults. We found impaired QoL in UK CAH adults and now report the relationship between QoL, glucocorticoid treatment and health outcomes in these patients.Methods: Cross-sectional analysis of 151 CAH adults with 21-hydroxylase deficiency aged 18–69 years in whom QoL (SF-36), glucocorticoid regimen, anthropometric, and metabolic...

Background: Acid-labile subunit (ALS) deficiency inhibits ternary complex formation leading to primary IGF1 deficiency and short stature. Potential metabolic consequences such as diabetes and low bone mass are not well studied.Objective: This study measured insulin sensitivity, lipid profile, bone density and structure in members of 4 affected families and explore possible gene-dose effects.Methods: Four patients (7–21 years) ...

We have previously reported the following metabolic abnormalities were common in 203 adult patients with CAH: obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%) and osteoporosis (7%) (Arlt et al. JCEM 2010 95 5110–21). The CAH patients were taking different glucocorticoid therapies at various doses (n=196): hydrocortisone (n=25 M, 26 W), prednisolone (n=21M,67W), dexamethasone (n=15M,22W) or comb...

Fetal Leydig cell (LC) dysfunction leads to human male reproductive disorders (‘testicular dysgenesis syndrome’; TDS) that manifest at birth (cryptorchidism, hypospadias) or in young adulthood (low sperm count, testicular germ cell cancer). The factors regulating fetal LC function in early gestation are unknown, but can be disrupted in rats by environmental chemicals (e.g. dibutyl phthalate (DBP)). We identify a novel repressor mechanism that explains this vulnerabil...

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...

Orbital fat (OF) represents a highly specialised adipose tissue depot that occupies a confined space behind the eyeball known as the orbit. OF fills most of the orbital cavity providing support to the delicate structures that link the eye to the brain, and protects against sight-threatening mechanical and inflammatory trauma. Subcutaneous (SC) and omental (OM) adipose tissues are highly active endocrine organs, regulated in part by glucocorticoids (GCs). The pre-receptor regul...

The preparation of Sandostatin LAR® injections using a 2 ml ampoule of vehicle solution may be associated with some technical difficulties of administration, with adverse consequences for patients. The development of a 2.5 ml prefilled syringe may alleviate some of these problems. We have compared these two methods of Sandostatin LAR® administration in 17 patients with acromegaly and 5 patients with neuro-endocrine tumours, (6 drug naïve, 1...

Graves' disease (GD) is caused by genetic and environmental factors. To date only the HLA class II region on chromosome 6p21 and the CTLA-4 gene on chromosome 2q33 have been consistently associated with disease. A recent study has indicated the most likely position of the aetiological variant in the CTLA-4 locus to be in a 6.1kb region of the 3' untranslated region of the gene. However the same degree of mapping resolution has not been achieved for the HLA class II region due ...

Intra-adipose steroid metabolism may be a key determinant of accumulation and distribution of body fat. Adverse 'central' fat can be driven by glucocorticoid excess or decreased oestrogen/androgen ratio. We previously demonstrated increased regeneration of cortisol by 11beta-HSD1 in adipose in human obesity. Here, we measured mRNAs for enzymes dictating local activation of oestrogens (aromatase) and androgens (5alpha-reductase type 1) in subcutaneous human adipose and related ...

A form of congenital adrenal hyperplasia (CAH) is associated with accumulation of steroid metabolites indicating impaired 17alpha-hydroxylase and 21-hydroxylase activities. However, sequencing of CYP17 and CYP21 genes does not reveal mutations, suggesting the involvement of a co-factor interacting with both enzymes. Affected females present with ambiguous genitalia at delivery, but circulating androgens are low and virilisation does not progress, a paradox yet to be explained....