Endocrine Abstracts

Pregnancy complications such as fetal growth restriction are associated with abnormal placental cell (cytotrophoblast) proliferation and apoptosis. Regulation of these events is unclear but recently we have used a placental explant model to demonstrate that IGFs influence cytotrophoblast kinetics and demonstrated that the protein tyrosine phosphatase (PTP) SHP-2 is required for IGF actions in the placenta. However, SHP-2 accounts for only 20% of total PTP activity, suggesting ...

Objective: The diagnosis of subclinical Cushing’s syndrome in patients with incidentalomas is not always straight forward and a number of different criteria have been used. The 1 mg overnight dexamethasone suppression test has been recommended as a screening test, followed up by other tests of the hypothalomo–pituitary–adrenal axis to confirm the diagnosis. In this study we investigate whether the low-dose dexamethasone suppression test offers additional informa...

CD38 is an enzyme which catalyses the production of the second messengers cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate which mobilize calcium from ryanodine-sensitive intracellular calcium stores. Intracellular calcium is well known to be important for mobilisation of secretory granules to the plasma membrane in preparation for exocytosis and CD38 signalling has recently been demonstrated to increase posterior pituitary oxytocin release (Jin et al.</i...

Uterine involution is a critical component of postpartum reproduction, which involves endometrial tissue repair, myometrial contraction and bacterial clearance. The uterus synthesises insulin-like growth factors (IGF-I and –II), IGF-I receptor (IGF-1R), and IGF binding proteins (IGFBPs -1 to -6) that regulate IGF bioavailability. This study used tissue from 12 multiparous Holstein-Friesian cows at day 14 postpartum to investigate expression of the uterine IGF system durin...

Patients with Grave’s disease (GD) are more prone to develop low serum calcium values than patients operated on because of goitre after total thyroidectomy. Moreover, some patients with GD achieve hypercalcemia probably due to active bone disease. We have used citrate-calcium clamping (CiCa) in order to investigate the calcium homeostasis in detail in patients with Grave’s disease.Material and method: Our series of patients undergoing total thy...

Topical glucocorticoid therapy causes adverse effects in human skin including a reduction in dermal fibroblast proliferation and extracellular matrix protein secretion (e.g. collagen 1) and epidermal thinning – effects paralleled in photoexposed and elderly skin. These cause reduced wound healing rates and a loss of elasticity with increased fragility and transepidermal water loss – signs also typical of Cushing’s syndrome characterised by raised circulating cor...

Our recent studies have localised 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1), which activates cortisol from cortisone, to the human ocular non-pigmented ciliary epithelium, and in an open blinded study conducted on healthy male volunteers, systemic inhibition of this isozyme with oral carbenoxolone (CBX) resulted in a 17% reduction of intraocular pressure (IOP). The aim of this study was to evaluate whether CBX reduced IOP in patients with ocular hypertension (...

Background: RACE is an open-label study that assessed the long-term safety and efficacy of recombinant human parathyroid hormone 1–84 (rhPTH[1–84]) for the treatment of hypoparathyroidism in adults (ClinicalTrials.gov identifier NCT01297309). Here, we present 6-year safety and efficacy data.Methods: Patients initially received 25 or 50 μg of rhPTH(1–84) subcutaneously, once daily, with stepwise dose adjustments of 25 μg (up or do...

Pituitary folliculo-stellate cells express annexin-A1 (ANXA1), a mediator protein necessary for glucocorticoid(GC)-induced negative feedback of adreno-corticotrophic hormone (ACTH) release. ANXA1 acts via formyl peptide receptors (FPR in man, Fpr in rodents). Whilst pituitary tissue does not express Fpr1, functional data suggested Fpr2/Fpr3-selective ligands mediate feedback-like inhibition of ACTH.Hypothesis: Fpr2-selective ligands inhibit secretagogue-...

Cinacalcet is a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism and parathyroid carcinoma. Multiple endocrine neoplasia type 1 (MEN1) patients may benefit considerably from cinacalcet. Affected patients have hyperplasia of multiple parathyroid glands, rather than a single resectable adenoma. Surgical cure requires removal of all parathyroid tissue, which is often unsuccessful, resulting in multiple neck explorations and hypoparathyroidism. Cinaca...