Endocrine Abstracts

Background: Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with incomplete penetrance. Heterozygote mutations have been identified in the aryl-hydrocarbon receptor interacting protein (AIP) gene in 20% of FIPA families causing young-onset aggressive tumours.Aims: The aim of this study was to perform comparative gene expression microarray analysis of familial AIP positive and AIP negative adenomas and compare them to sporadi...

AMPK is a key regulator of cellular and body energy homeostasis. We previously demonstrated that AMPK activation in osteoblasts increases bone formation in vitro while deletion of the AMPKα1 subunit leads to decreased bone mass in vivo. To determine whether bone turnover can be stimulated in the absence of AMPKα1 subunit, we subjected WT and AMPKα1−/− mice to catabolic (ovariectomy: OVX) and anabolic (intermittent PTH adminis...

GH influences multiple metabolic pathways. Excess GH (acromegaly) causes a distinct form of cardiomyopathy, which may progress to fulminant heart failure. AMPK is an energy conservation enzyme that modulates multiple areas of the cell stress response, inhibiting anabolism and promoting catabolism. AMPK is activated by phosphorylation at Thr172 and measurement of Thr172 phosphorylation is thought to correlate with enzyme activity. We investigated the influence of GH on cardiac ...

Pituitary adenomas are benign tumours, which do not involve mutations in tumour suppressor genes or oncogenes. We have shown that the canonical Raf/MAPK and PI(3)K/Akt pathways are over-activated in these tumours, but their downstream effectors are modified to a much lesser extent. It is probable that the oncogenic mutations responsible for the initiation of these tumours therefore lies proximal to the convergence of these pathways, at or even upstream to the growth factor rec...

Several hormones, including cortisol, have a circadian rhythm in plasma and saliva. Salivary cortisol is now extensively used for screening and following patients with various conditions where the regulation of hypothalamo-pituitary–adrenal axis is abnormal, for example in major depression where salivary cortisol levels show a disruption or loss of the circadian rhythm.Annexin 1 is a glucocorticoid-induced protein, which is responsible for mediating...

Introduction: Genomic testing is expected to become a part of mainstream testing in the not-too-distant future, with clinicians ordering genetics tests in the same way routine endocrine tests are requested today. Knowledge on how and what test to request needs to be gathered by a wide range of physicians. To support this, the Genomics Education Programme of NHS England is developing a resource for all endocrinologists to use in clinic as part it’s Genomic...

Introduction: In children, tumours occupying the pituitary fossa are mainly craniopharyngioma (80–90%) and pituitary adenomas (2–3%). We present two cases of pituitary adenoma and the challenging management when complete surgical resection is not possible. Case 1: A 13.5 year old girl presented with tall stature. Pituitary hormone profile revealed high IGF1 123 nmol/l (24.5–66) and prolactin 722 mU/l (102–496). Growth hormone (GH) was not completely suppres...

Introduction: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose humans to pituitary adenomas, mostly GH and sometimes prolactin-secreting adenomas. Rodent models of heterozygous AIP loss provided mixed results, with little phenotype in heterozygote global knockouts to 80% in somatotroph-specific homozygote knockout animals. However, human patients with an AIP mutation often have mixed GH-PRL adenomas and, in a smaller pr...

Introduction: Androgen insensitivity syndrome (AIS) is a heterogeneous condition. At the milder end of the clinical spectrum, patients with mild AIS (MAIS) are phenotypically male, and may present with infertility, either isolated or associated with gynaecomastia or signs of mild undervirilization. Most cases of complete and approximately 25% of partial AIS patients harbour mutations in the androgen receptor (AR) gene. Over 1,000 pathogenic variants have been describe...

Introduction: Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose humans to pituitary adenomas, mostly GH and sometimes prolactin-secreting adenomas. Rodent models of heterozygous AIP loss provided mixed results, with little phenotype in heterozygote global knockouts to 80% in somatotroph-specific homozygote knockout animals. However, human patients with an AIP mutation often have mixed GH-PRL adenomas and, in a smaller pr...