Endocrine Abstracts

Kisspeptin, the endogenous ligand of the GPR54 receptor, is a key regulator of reproduction. Inactivating mutations of the GPR54 receptor in mice and humans is associated with a failure of reproductive function. Activating mutations in the GPR54 receptor result in precocious puberty. The endogenous neuropeptide agonist for GPR54, kisspeptin, potently stimulates release of gonadotrophins in rodents and primates.Objective: We determined the effects of elev...

A 65 year old lady presented to her GP in 1997 with an extensive rash. She was referred to a dermatologist but the rash which failed to settle with topical treatments. A plasma glucagon level was elevated at 275 pmol/l (NR 0-50). CTscan revealed a mass in the pancreatic tail and hepatic metastases consistent with malignant glucagonoma. She was commenced on octreotide and the rash resolved. She underwent a distal pancreatectomy, partial left hepatic lobectomy and intraoperative...

Headaches associated with acromegaly are common even after hypophysectomy. Medical treatment with dopamine agonists and Somatostatin analogues often help. We report two cases when pharmacological therapy failed but further surgical removal of residual pituitary tissue cured the headaches.A 38 year-old lady presented with an eight year history of headaches, unresponsive to simple analgesia. Acromegaly was confirmed by a raised serum growth hormone (GH) 33...

Background: Hyperprolactinaemia accounts for 1 in 7 patients presenting with amenorrhoea. Recent data suggests that prolactin acts at the hypothalamus to reduce GnRH-pulsatility. Conditions in which GnRH-pulsatility is reduced, such as hypothalamic amenorrhoea, favour FSH over LH secretion from the pituitary gland. We examined gonadotrophin secretion in hyperprolactinaemic patients as a surrogate marker of GnRH-pulsatility.Methods: A retrospective analys...

Background: The hypothalamus is a critical area of the brain involved in the regulation of appetite. Cerebellin1 (Cbln1) is a highly conserved 16 amino acid neuropeptide. High levels of Cbln1 mRNA expression are found in specific hypothalamic areas involved in appetite regulation.Aim: To examine the effects of Cbln1 on food intake in rodents.Methods: 1. Ad libitum fed rats were injected intracerebroventricularly (ICV) with Cbln1 (1...

A 59-year-old lady presented with significant weight gain, and a history of hypertension for investigation of possible Cushing’s syndrome. Her BMI was 29, with mainly central obesity. Initial tests revealed elevated untimed cortisol on two separate occasions, at 905 nmol/l and 893 respectively with detectable midnight cortisol, at 548 and 481. Of 24-hour urinary free cortisol (UFC) was also elevated on two separate occasions, at 931 nmol/24 h and 827 respectively. ACTH wa...

The definition of early cure post transphenoidal surgery (TSS) for Cushing’s disease continues to be debated. The low dose dexamethasone suppression test with corticotrophin releasing hormone (LDDST-CRH) is a test for diagnosis of Cushing’s; however it has not been validated in early post TSS to determine remission. The aim of this study was to determine whether the combined LDDST-CRH test could be used in post TSS patients.The combined LDDST-C...

The rising prevalence of obesity and type II diabetes makes the diagnosis of Cushing’s syndrome increasingly difficult. The dexamethasone-suppressed corticotrophin-releasing hormone (CRH) test, which involves CRH administration immediately following a standard low dose dexamethasone suppression test (LDDST), has been reported to diagnose Cushing’s syndrome with 100% sensitivity and specificity. We adapted our LDDST protocol to include CRH administration post-dexameth...

Agouti-related protein (AgRP) and neuropeptide Y (NPY) are co-localised in hypothalamic arcuate nucleus neurons that have been implicated in the regulation of energy balance. Both AgRP and NPY stimulate food intake when administered into the third ventricle and are up-regulated in states of negative energy balance e.g. fasting. AgRP/NPY neurones are thought to play a role in the integration of information received from circulating satiety factors and signals of energy store st...

Kisspeptin is the peptide product of the KiSS-1 gene and endogenous agonist for the GPR54 receptor. The kisspeptin/GPR54 system has recently been suggested as a key regulator of the reproductive system. GPR54 deficient mice have abnormal sexual development and low circulating gonadotrophins and in humans, GPR54 mutations have been shown to cause hypogonadotrophic hypogonadism. Thus, GPR54 appears to be essential for normal gonadotrophin secretion and the regulation of puberty....