Endocrine Abstracts

Introduction: • The incidence of primary hyperparathyroidism (PHPT) in Scotland is approximately 3.5/100 000 per year.• The incidence is probably on the rise due to increase in ‘routine biochemical testing’• Some patients tend to undergo surgery, while others are conservatively treated and most followed up for a short period before discharge from follow up.Aims: • Determine if ri...

Aims and objectives: Patients with thyroid dysfunction typically require frequent monitoring of thyroid function tests in order to titrate drug treatments and achieve normal thyroid function. A nurse-led thyroid telephone consulting service was established in 2006 to allow monitoring of thyroid function tests without the need for a hospital doctor’s appointment, with the aim of offering increased convenience for patients as well as significant cost savings. This audit aim...

We recently demonstrated that fetal programming changes induced by a maternal low protein diet (MLP) that lead to the development of hypertension in the rat offspring were associated with increased expression of the AT1b angiotensin receptor (AT1b) and reduced methylation of its promoter in the adrenal gland. Previous findings have suggested that overactivity of the maternal pituitary–adrenal axis in pregnancy results in overexposure of the fetus to glucocorticoids which ...

Background: The growth hormone receptor (GHR) 6Ψ pseudoexon mutation (A to G at ds-1) is one of the most frequent mutations causing GH insensitivity. It causes aberrant mRNA splicing, leading to activation of a pseudoexon and insertion of 36 additional amino acids, resulting in a functionless receptor. Although IGF-I remains the mainstay of treatment for these patients we investigated the ability of RNA antisense oligonucleotides (ASOs) to correct aberrant GHR splicing us...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by ACTH resistance resulting in isolated glucocorticoid deficiency with preserved mineralocorticoid secretion. Approximately 25% of cases result from mutations in the ACTH receptor (MC2R) and 20% result from mutations in the Melanocortin 2 receptor accessory protein (MRAP). MRAP is a small single transmembrane domain protein that is specifically required for trafficking MC2R to the ce...

Introduction: Silver–Russell Syndrome (SRS) is a heterogeneous condition characterised by low birth weight, postnatal growth failure and clinical features including relative macrocephaly, limb or facial asymmetry and a triangular facies with broad forehead, pointed chin and downturned mouth. SRS been linked to a number of genetic abnormalities including maternal uniparental disomy (UPD), of chromosome 7 and hypomethylation of the IGF2-H19 imprinted region on chromosome 11...

Mutations in the ACTH receptor (Melanocortin 2 receptor/MC2R) are associated with Familial Glucocorticoid Deficiency/FGD. FGD is an autosomal recessive disorder that results from ACTH insensitivity at the adrenal cortex. However, only about 25% of FGD are caused by mutations in the MC2R suggesting the genetically heterogeneous nature of the disease. The transfection-mediated functional expression of the MC2R can only be achieved in cell lines of adrenal origin implying that th...

Familial Glucocorticoid Deficiency type 2 (patients with normal MC2R) is associated with mutations in the MRAP (Melanocortin Receptor Accessory Protein) gene. In order to investigate the function of this novel single transmembrane domain protein, CHO and SKN-SH cells were transfected with MRAP-FLAG and/or MC2R-GFP constructs and imaged using confocal microscopy. Although the MC2R-GFP failed to be expressed at the cell surface when transfected alone, it was found to be expresse...

The peptide hormone ACTH stimulates lipolysis and suppresses leptin production in adipocytes via the G-protein coupled seven transmembrane receptor, MC2-R. We have shown previously that PPARγ2 is the primary factor responsible for transactivation of the already identified murine MC2-R promoter in the differentiating 3T3-L1 adipocyte cell line. In this study we show that despite the activity of this promoter being transient during differentiation, MC2-R mRNA remains elevat...

The high dose short Synacthen (corticotropin) test (SST) is widely used to investigate suspected secondary adrenal insufficiency but concern remains about falsely reassuring results with potentially serious clinical consequences.In order to evaluate the long-term safety of the SST, we retrospectively evaluated the clinical outcome in 178 patients who achieved 30-minute cortisol values in the lowest 15th percentile of normal healthy responses. This subgro...