Endocrine Abstracts

Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 30% of pituitary gigantism cases. However, pathological accelerated growth and/or tall stature can be unrelated to the growth hormone (GH) axis, and may occur in isolation or as part of a syndrome, such as in Klinefelter, Marfan or Sotos syndromes. We report a five-generation kindred with two brothers with pituitary gigantism due to AIP mutation-positive GH-secreting pi...

A 34-year-old male with two decades of gender identity issues considered gender reassignment and attended pre-orchidectomy sperm-banking when he was found to be azoospermic. He described a history of difficulty learning to play the piano and of deep-vein thrombosis at 19 years. He was 187 cm tall with a span of 189.7 cm, and exhibited L-sided undescended testis, R testis 1.8×2.5×3.7 cm, bilateral prominent gynaecomastia, a female body habitus, micropenis, bimanual sy...

Background: Familial isolated pituitary adenoma (FIPA) is recently identified autosomal dominant condition with incomplete penetrance. Heterozygote mutations have been identified in the aryl-hydrocarbon receptor interacting protein (AIP) gene in 20–30% of FIPA families. AIP mutation positive patients have distinct phenotype: the disease is occurring at a younger age and have more aggressive tumours.Aims: The aim of this study was to perform comparat...

Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene predispose to early onset pituitary adenoma, with a preponderance of somatotrophinomas. Patients harbouring an AIP mutation respond poorly to somatostatin analogue (SSA) treatment. On the other hand, a subset of sporadic somatotrophinomas with no AIP mutations show low AIP protein expression and exhibit a decreased response to SSA treatment as well. microRNAs are small...

A 29y female presented with an 8y history of hypomagnesaemia. It was noted incidentally when hospitalised with mumps-related pancreatitis. Subsequently symptomatic hypomagnesaemia, with headaches and lethargy, was treated with magnesium glycerol phosphate 4 mg TDS, but she remained symptomatic with occasional need of IV Mg2+. It was thought that she was poorly compliant with her oral Mg2+ supplements. At presentation to our department for follow-up of her...

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...

Introduction: Since there is no completely effective therapy available for malignant phaeochromocytomas (PCCs) and paragangliomas, we have been investigating novel targeted therapies utilising one more benign (MPC) and one more malignant (MTT) PCC cell line. We have previously shown that the IGF1-receptor-inhibitor NVP-AEW541 led to compensatory ERK and mTORC1 up-regulation at suboptimal doses and that the dual PI3K/mTORC1-inhibitor NVP-BEZ235 also resulted in compensatory ERK...

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...