Endocrine Abstracts

Background: The human adrenal cortex is composed of different zones, namely the zona glomerulosa (ZG), zona fasciculata (ZF), zona reticularis, and the recently proposed undifferentiated zone (UZ). The adrenal cortex synthesises and secretes steroids, mainly aldosterone and cortisol, both responsible for essential physiological and metabolic functions. Adrenal cortex disorders can be life threatening and current treatment involves life-long steroid replacement, which is not id...

The adrenal cortex is the primary site of steroid synthesis, producing glucocorticoids under the control of the hypothalamic–pituitary axis and mineralocorticoids under the control of the renin–angiotensin system.Adrenal insufficiency, which can be life threatening, is cause by a number of adrenal disorders, and lifelong management of these patients with exogenous steroids can be challenging. No drug suitably mimics the diurnal pattern of corti...

Introduction: The Sonic hedgehog (Shh) pathway is an evolutionarily conserved signalling pathway, playing an essential role during embryonic development. Murine studies have shown the importance of Shh in the growth of the adrenocortical primordium. Shh expression has previously been described in relatively undifferentiated sub-capsular cells in the developing rodent adrenal, however the organisation of the human foetal adrenal (HFA) is unique. This novel study aimed to descri...

Background: Familial Glucocorticoid Deficiency is an autosomal recessive disorder characterised by ACTH resistance of the adrenal cortex, leading to isolated glucocorticoid deficiency. Causative genes include MC2R, its accessory protein MRAP and StAR which account for 50% of cases. Recently nicotinamide nucleotide transhydrogenase (NNT) has been associated with a further 10% of cases. NNT generates the high concentrations of NADPH in mitochondria necessary for detoxification o...

The melanocortin-2-receptor accessory protein (MRAP) is a type I integral transmembrane protein required for the functional expression of the melanocortin-2-receptor (MC2R).Here we have investigated the expression and biochemical properties of mouse MRAP. Initially, mouse MRAP and MC2R tissue expression were determined by RT-PCR, being only present in the adrenal gland and fat tissue. Then, by in situ hybridisation studies using a full-length MRAP...

Background: Aberrations in the timing of puberty may result in significant adverse health outcomes, including cancers, cardiovascular and neurological pathologies. Self-limited delayed puberty (DP) (i.e. constitutional delay of puberty) runs in families with either autosomal dominant or complex inheritance patterns in >70% of families, indicating a strong genetic basis of the trait. However, only a few genes have been identified underlying DP so far....

Introduction: A unique variant of familial glucocorticoid deficiency (FGD) exists in the Irish travelling community, a genetically isolated population with high levels of consanguinity. Affected children develop hypocortisolaemia and raised ACTH but retain normal renin and aldosterone levels. Children also have short stature, evidence of increased chromosomal breakage and natural killer cell deficiency.Methods: We sought areas of homozygosity common to a...

The adrenal cortex is a dynamic organ that undergoes self-renewal. In the mouse it is divided into two concentric layers, the outer zona glomerulosa (ZG) and the inner zona fasciculata (ZF), that secrete aldosterone and corticosterone, respectively. Capsular and subcapsular stem/progenitor cells differentiate and migrate in a centripetal fashion to repopulate the gland until they reach the juxtamedullary region where they undergo senescence and apoptosis. Our lab has previousl...

Background: The initiation of puberty is heralded by increasing gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. During embryonic life the GnRH neuroendocrine network develops thanks to a coordinated migration of neurons from the nasal placode to the forebrain. Our group has previously demonstrated that dysregulation in GnRH neuronal migration leads to delayed pubertal onset. Late puberty affects up to 2% of the population and is associated with adverse h...

Case history: A 63-year-old female presented with bi-temporal hemianopia. Pituitary MRI demonstrated a macroadenoma with suprasellar extension. Her medical history included a glomus tumour of the right ear treated with external beam radiotherapy (EBRT) 25 years previously. She had no evidence of pituitary hormone abnormality and had normal urinary metanephrines levels. She underwent transsphenoidal surgery with total resection and full recovery of her visual fields. Immunohist...