Endocrine Abstracts

Acromegaly is caused by excessive growth hormone (GH) secretion frequently due to GH-secreting pituitary tumors. Acromegalic tumors (ACRO) display reduced microvascular density versus normal pituitaries, suggesting they are under hypoxic conditions. Under hypoxia, tumors gain a survival advantage by stabilizing the transcription factor known as hypoxia-inducible factor 1 alpha (HIF1a). Western blot screening of ACRO (n=40) revealed significantly higher HIF1a protein l...

SSTR2 is one of the main pharmacological target for GH-secreting pituitary adenomas treatment and the cytoskeletal protein FLNA plays an important role in tumor responsiveness by regulating SSTR2 expression and signaling. Single-Molecule Imaging was used to investigate the spatial distribution of FLNA-SSTR2 at the plasma membrane level and the involvement of FLNA in SSTR2 mobility, receptor clustering organization/internalization. This method is based on labeling SNAP/CLIP-tag...

: Hypothalamic regulation of pituitary adrenocorticotropic hormone (ACTH) secretion switches to dopamine (DA) with a parallel loss of DAerg control of alpha-melanocyte-stimulating hormone (α-MSH) release in lactating dams. It has been also shown that dephosphorylation/inactivation of tyrosine hydroxylase (TH) in terminals of DA neurons at the median eminence is required not only for suckling-induced PRL release but also for ACTH responses. The aim of the present study was...

We have recently shown that patients with growth hormone (GH) excess (acromegaly) exhibit inadequately low intrahepatic lipid content (IHL) despite marked insulin resistance. GH might increase mitochondrial oxidation capacity thereby counteracting ectopic lipid accumulation; however, up-regulation of mitochondrial function has been reported in early stages of non-alcoholic fatty liver disease. Up to now, data on mitochondrial activity in patients with acromegaly are missing.</...

Somatostatin analogues (SSAs) approved to treat acromegaly tend to suppress postprandial insulin/glucagon secretion and can worsen glucose tolerance. COR-005, a novel SSA, is under investigation for treatment of acromegaly. In rodents, COR-005 effectively inhibits GH secretion with 10,000-fold greater potency compared with insulin release suppression. We sought to determine for the first time the effects of COR-005 on postprandial glucose in humans.The p...

Introduction: Clinical observational studies have reported the persistence of a high cardiovascular risk in patients with cured Cushing’s syndrome (CCS) compared with controls of the same age, gender and BMI. It is still at debated whether this is due to the persistence of comorbidities, hormone deficiencies or chronic changes induced by hypercortisolism. The aim of this translational approach was to investigate the interplay in CCS of the cardiovascular disease in vivo a...

: Nonfunctioning pituitary adenomas (NPA) are prevalent neoplams from pituitary. The best treatment is the surgical approach but residual tumours are common. For residual tumours the options are radiotherapy (RT) and re-surgery. There are no significant studies testing drugs in NPA. Due to the fact that these tumors express dopamine D2 receptors, dopamine agonists that may be useful in patients with NPA.Methods: We selected 145 patients with residual tum...

Introduction: Prader–Willi syndrome is a genetic disorder characterized by hypotonia, intellectual disabilities, obesity and behavioral disturbance. Patients present with several neuroendocrinological abnormalities, such as growth hormone deficiency, hypogonadotropic hypogonadism, and hyperphagia, as the result of possible involvement of the hypothalamo-hypophyseal system. Diffusion tensor imaging (DTI) is a noninvasive MRI technique capable of providing quantitative indi...

The G protein-coupled receptor (GPCR) kinase 2, GRK2, is a ubiquitous serine/threonine protein kinase that is able to phosphorylate and desensitize the active form of several GPCR. Compelling, as yet limited, evidence from in vitro studies have suggested a potential role of GRK2 in mediating desensitization of Gpr54, the canonical receptor for kisspeptins that is abundantly expressed in GnRH neurons. Yet, although kisspeptins have been universally recognized as essent...

Introduction: PATRO adults is an international, longitudinal, non-interventional study of the long-term safety and efficacy of recombinant human growth hormone (rhGH; Omnitrope®, Sandoz). The study will provide additional data on the long-term safety of rhGH in adult patients with severe GH deficiency (GHD). Here, we present safety data from an interim analysis.Methods: Eligible patients are adults who are receiving treatment with Omnitro...