Endocrine Abstracts

Annexin 1 (ANXA1) is a 37 Kd member of the annexin family of Ca2+− and phospholipid binding proteins that has been well demonstrated to act as a mediator of glucocorticoid action in inflammation and in the control of anterior pituitary hormone release. ANXA1 is also proapoptotic and has been identified as a mediator of apoptotic cell engulfment (Solito et al. 2003 FASEB J 17:1544; Arur et al. 2003 Dev Cell 4:587). Using yeast two hybrid screening...

67-year-old man re-attended A&E following minor head injury with disproportional symptoms of dizziness on sitting upright, vomiting and neck pain. He is also complaining of nasal blockage for past 1 year with anosmia and occasional yellow rhinorrhoea. On examination he has mild neck tenderness and cranial nerves were intact. Nasopharyncoscopy revealed fullness of posterior nasal space.Head CT was performed revealing extensive soft tissue tumour appea...

The novel somatostatin receptor agonist SOM230 (pasireotide) binds with high affinity to somatostatin receptors sst1, sst2, sst3 and sst5. Acting principally through the latter, it inhibits basal and CRH-stimulated ACTH secretion from the AtT20 mouse corticotroph cell line and ACTH release from a proportion of human corticotroph adenomas both in vitro and in vivo. Data suggesting an additional antiproliferative effect has led to SOM230 being explored as a potenti...

Background: Surgery, sometimes supported by adjunctive radiotherapy (RT) are the treatments of choice for patients with non-functioning pituitary adenomas (NFA). Previous studies have implicated these treatments in deficits of cognitive function, particularly memory and executive functioning, although this research has often been confounded by the inclusion of patients with hormone producing tumours. The aim of this study was to determine the impact of RT on psychometric funct...

Introduction: The incidence of water and electrolyte disturbances following traumatic brain injury (TBI) is considerable and has been attributed to a dysregulation of the hypothalamic peptide arginine-vasopressin (AVP). Copeptin, the C-terminal part of the AVP prohormone, is stoichiometrically secreted together with mature AVP. Due to his long ex vivo stability, the AVP precursor, copeptin, can be used as a surrogate of AVP readily to be measured in serum or plasma. In ...

Purpose: Neuroendocrine dysfunction represents a frequent consequence of traumatic brain injury (TBI) but has not been studied longitudinally as yet. Here we attempt to identify predictors of late endocrine insufficiency following TBI.Methods: 71 consecutive patients (age 18 – 87 yrs) with TBI assessed by an intial CT and the Glasgow Coma Score (GCS) were prospectively studied as to their pituitary function on day 0, 3 and 7 and dynamically 24–...

Relaxin-3 is a newly discovered member of the insulin superfamily. It is expressed in the nucleus incertus (NI) of the brainstem which has projections to the hypothalamus. Relaxin-3 binds with high affinity to the G-protein-coupled receptors RXFP1 and RXFP3. RXFP3 is expressed predominantly in the CNS, and in particular within the hypothalamic paraventricular nucleus (PVN). The physiological function of relaxin-3 is unknown but recent work suggests it may play a role in appeti...

Folliculostellate (FS) cells within the anterior pituitary gland produce cytokines and growth factors which are regulated by molecules produced by neighbouring endocrine cells. There are many factors that could potentially be responsible for this intercellular communication that is mediated via connexins (Cx) and gap-junctions. We thus investigated the effect of co-culturing lactotrophs (MMQ) and FS cells (TtT/GF) on Cx43 expression. Our in vitro model system consists o...

In the central nervous system, the opioid and non-opioid transmitter system jointly compete with multiple pathophysiological processes. The in vitro neuronal model of rat (Wistar) caudate putamen and reverse transcription-poly-merase chain reaction were used to examine the effects of neurotensin and/or morphine on the expression of mu or delt-opioid receptor mRNA. In the present study neurotensin (10 nmol/l) promoted but morphine (0.001 mmol/l) reduced mu or delt-opioid...

Females release 2–3 fold greater GH compared with males whilst maintaining similar IGF-I levels. IGF-I generation tests in healthy subjects suggest this discordancy results from resistance to GH in females. In GHD females the presumed relative insensitivity to GH is reflected by a lower basal IGF-I and higher GH maintenance doses during replacement. GHD adults of childhood- (CO) and adult-onset (AO) show CO-GHD adults to have lower basal IGF-I values and require higher ma...

PYY is secreted postprandially from the endocrine L-cells of the gastrointestinal tract. PYY3–36, the major circulating form of PYY, reduces food intake in humans and rodents via high affinity binding to the auto-inhibitory NPY receptor, Y2R, within the hypothalamic arcuate nucleus.Aims: To investigate (1) the effects of length of fast on the anorexigenic actions of PYY3–36; (2) the effects of early light phase administrat...

The pre-receptor regulation of glucocorticoids is mediated by 11β-hydroxysteroid dehydrogenases (11β-HSD). The type 1 isoform is primarily responsible for the generation of active cortisol in tissues such as liver and adipose, whereas 11β-HSD2 regulates sodium and ion transport. Recently, we have shown the presence of functional 11β-HSD1 in the ciliary body of the eye where it is important in control of sodium transport, aqueous humour production and intrao...

The aim of the investigation was to evaluate the effect exogenous of 17-β-estradiol propionate (E2) on working memory as assessed by the novel object recognition (NOR) paradigm following intermittent or delayed E2 regimens.15 rats were ovariectomised under anaesthesia and were divided into 3 groups namely: (1) vehicle (2) intermittent E2 dosing weeks 1–6 and 13–18, with no treatment weeks 7–12 and (3) delayed (no treatment in weeks 1&...

Case History: A 16 yr old patient presented to us concerned about her short statue. Her father and mother were at the 9th centile and her sister was at the 25th centile in adult life. She was otherwise well having gone through a normal puberty in her early teens and was currently on the oral contraceptive pill having regular periods. On examination she did display some features of Turner’s syndrome; short stature, short neck and cubitus valgus deformity. Cytogenetic analy...

Road traffic accidents resulting in traumatic brain injuries are increasingly common. Patients are often males in their third decade. Many of these patients persist to have various symptoms even after recovery from the acute phase, which tend to be diagnosed as post concussion syndromes. Interest has increased of late in Post traumatic hypopituitarism. We report two patients with head injuries with endocrine insufficiencies.A 21 year male was hit by a ca...

Primary resistance to Cabergoline occurs in a minority of patients with lactotroph adenomas but the development of late resistance following initial response is an extremely rare phenomenon which has only been reported in very few cases.: We report the case of a 57 year old lady who was presented in 1997 with headaches and visual failure and was found to have a large pituitary mass with compression of the optic chiasm and invasion into the cavernous sinuses bilaterally. Serum ...

There are discrepancies between different studies with regards to the association of subclinical hypothyroidism (SCH), dyslipidaemia and cardiovascular (CV) disease. Therefore, we have conducted a systematic search and meta-analysis of population-based studies of CV disease in which thyroid status was examined and randomised controlled trials (RCTs) of treatment.The PubMed and Embase databases were searched for relevant studies published between 1976 and...

Establishing failure of trans-sphenoidal surgery (TSS) to cure Cushing’s disease in the immediate post-operative period is essential for early surgical re-exploration. However, there is no consensus regarding the definition of apparent cure. We studied whether the dexamethasone-suppressed corticotrophin-releasing hormone test (LDDST-CRH test) immediately following TSS could accurately identify those with Cushing’s disease requiring further definitive treatment.<p...

Objective: Macroprolactinomas (MPRL) may result in spontaneous or dopamine-agonist-induced CSF rhinorrhoea. The incidence of, and mechanisms underlying this phenomenon are poorly understood. In this study, we aimed to determine the incidence of non-surgical (spontaneous and dopamine-agonist-induced) rhinorrhoea, and to identify biochemical, radiological and histopathological factors associated with this phenomenon.Methods: We retrospectively reviewed MPR...

CNP, the third member of the mammalian natriuretic peptide family, exerts the majority of its biological effects via the guanylyl cyclase B (GC-B) receptor, resulting in accumulation of intracellular cGMP. Previous studies reveal numerous inhibitory effects of natriuretic peptides on the MAPK family in bone, neuronal and cardiovascular tissues. However, we recently reported that CNP stimulates ERK, p38MAPK and JNK phosphorylation in pituitary GH3 somatotrophs. As CNP is known ...

In patients with pituitary disease stimulation tests, such as the insulin tolerance test, are performed as tests of the HPA axis and widely used as the basis for commencing hydrocortisone replacement therapy.We conducted a pilot study to investigate the relationship between the peak cortisol response to insulin-induced hypoglycaemia and daily CPR. Isotopic CPRs were studied in 10 patients (5 male, mean age 44±13 years) with pituitary disease and a s...

Respiratory disorders are a major cause of illness and impaired physical function in patients with acromegaly, contributing to 25% of all recorded deaths, with respiratory mortality 3-fold higher than in normal subjects. Sleep apnoea (SA), the phenomenon of recurrent cessation or decrease of airflow to the lungs during sleep, is the commonest reported respiratory complication. Both obstructive (OSA) and central (CSA) sleep apnoeas are known to occur, although the overall preva...

Introduction: Pro-opiomelanocortin (POMC) is a precursor polypeptide which is cleaved to make adrenocorticotrophic hormone (ACTH) in the anterior pituitary. It is activated in Cushing’s disease. Current therapies for Cushing’s disease are inadequate. RNA interference (RNAi) allows highly specific and effective suppression of gene expression by use of short interfering RNAs (siRNAs).Method: In the current study we employed custom designed siRNAs...

Objective: Our aim was to identify and treat sleep disorders in asymptomatic patients with craniopharyngioma and to identify co-existing respiratory disease.Methods: 5 patients (1 male) with a diagnosis of craniopharyngioma, were identified from the local pituitary database and admitted for polysomnography (Alice 4, Respironics), as part of a study of hypothalamic disease in craniopharyngioma. Sleep disturbance was defined as an apnoea index (AHI) of &#6...

Patients with acromegaly die prematurely from CVD. Hypertension is more prevalent with increased peripheral vascular resistance thought to be due to structural remodelling of resistance vessels.We investigated structural properties and reactivity of small arteries in 20 healthy controls(55±11 years, 10 m) and 43 patients with acromegaly (55±14 years, 29 m), split into active disease (AD, n=17, 56±15 years, 13 m) or remission (CD, <i...

Two patients presented to us with polyuria and polydipsia.Case 1– A 34 year old gentleman was referred with polyuria, polydipsia, diffuse headaches and poor sleep. Initial plasma and urine osmolality were 306 and 272 milliosmol/kg respectively. Water deprivation test demonstrated normal concentrating ability. Starting urinary osmolality was 788 milliosmol/kg, rising to 877 milliosmol/kg. MRI pituitary was normal. Hypertonic saline infusion test prod...

Acromegaly is almost always due to a sporadic growth-hormone secreting pituitary adenoma, but familial acromegaly has been reported occasionally. Linkage and loss of heterozygosity studies have suggested that it is caused by a tumour suppressor gene located at 11q13. Recently mutations have been identified in a gene in some families with acromegaly alone or acromegaly and prolactinoma. The gene codes for the aryl hydrocarbon receptor interactive protein (AIP), a molecular chap...