Endocrine Abstracts

The insulin tolerance test (ITT) is the gold standard for assessing growth hormone (GH) and cortisol production in pituitary disease, However it is potentially hazardous, requires medical supervision and adequate hypoglycemia may not be achieved. We retrospectively examined the records of 185 consecutive patients aged 14-76 years with pituitary disease who underwent the ITT over 18 months. Testing was performed in the endocrine day ward by an experienced endocrine nurse. Absol...

Hypopituitarism is associated with premature vascular mortality. Growth hormone (GH) deficiency, over-replacement with glucocorticoid, cranial irradiation and traditional vascular risk factors are possible contributing factors to the excess mortality.We studied 200 consecutive adult hypopituitary age (mean standard deviation) 51.7 plus/minus 15.3 years, who attended our pituitary clinic between July and December 2002. Hypertension was defined as blood pr...

Background:.Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) was designed for use in patients with GHD, a condition characterized amongst other things, by impairment in QoL. For use in cost-utility analysis outcomes should be measured on a scale of social preferences that assigns values of 1 and 0 to full health and dead. Condition-specific instruments may generate summary index scores but typically lack the legitimacy for use as measures of QoL ou...

Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI), tested several months or longer after the event. No information is available on the frequency of hypopituitarism in the immediate post-TBI period.We studied 50 consecutive patients who were admitted to the neurosurgical unit with severe or moderate TBI [initial Glasgow Coma Scale (GCS) score 3-13]. Testing was performed at a median of 12 days pos...

Two members of the melanocortin (MC) receptor family are abundantly expressed in the adrenal cortex, namely MC2R and MC5R. MC2R binds only ACTH and is known as the ACTH receptor, the role of MC5R however is still under investigation. It is known that alpha-MSH stimulates aldosterone secretion by the rat adrenal cortex, by an MC2R-independent mechanism, although the receptor involved has not been identified. The experiments were designed to investigate the role of MC5R in the a...

Background: Although the negative impact of GHD in adults on quality of life (QoL) is well recognized and it has become routinely measured in clinical practice, there is still limited information about the extent of the differential between adults with GHD and their age/sex-matched peers within the general population.Objectives: The study was designed to test the discriminatory power of QoL-AGHDA by determining normative reference values in the general p...

The syndrome of inappropriate antidiuretic hormone (SIADH) is characterised by euvolamic hyponatraemia. Patients with SIADH continue to drink normal amounts of fluid, despite plasma osmolalities well below the physiological osmotic threshold for the onset of thirst. The regulation of thirst has not been previously studied in SIADH. We studied the characteristics of osmotically-stimulated thirst and vasopressin (AVP) secretion, and the non-osmotic suppression of thirst and AVP ...

Hereditary nephrogenic diabetes (di/di) in mice results from a failure of vasopressin (VP)action caused by overactive renal cAMP phosphodiesterase activity. The adult animals pass large amounts of dilute (100 mOsm per kg) urine and have hyperosmotic plasma (40 mOsm per kg greater than wild-type). Their osmotic status is therefore similar to that in Brattleboro rats in which both VP and oxytocin (OT) neurons are hyperactive and the neural lobe is depleted of both OT and VP. The...

It has been noted that there are differences in the hypothalamic-pituitary-adrenal (HPA) axis between the sexes, as well as changes in the axis with age. The differences in the HPA axis between the gender and age groups are thought to be due to differences in the efficiency of glucocorticoid (GC) negative feedback. The pituitary, a principle site of GC negative feedback, is the focus of this investigation. Annexin-1 (ANXA1) is a member of the annexin family of phospholipid- an...

Recent evidence suggests a high prevalence of neuroendocrine dysfunction in patients following traumatic brain injury (TBI), but dynamic anterior pituitary assessment were performed in relatively small number of patients and posterior pituitary function remains poorly investigated.We studied 102 consecutive patients (84 males) who had survived severe or moderate TBI [initial Glasgow Coma Scale (GCS) score 3-13] at a mean (+/- standard deviation) of 19 +/...

Oral but not transdermal ORT reduces serum IGF-1 levels in postmenopausal women. The effect of ORT type on GH dose and sensitivity is unclear. We present a retrospective analysis of GH-deficient women on ORT in the KIMS database.AIM: To determine the type of oestrogen prescribed and its effect on GH dose.METHOD: Patients were divided into groups taking oral oestradiol valerate, conjugated oestrogen, ethinyloestradiol and transderma...

Neuroendocrine tumours are uncommon and often present difficult therapeutic challenges. They may be composed of different cell types and are often multihormonal. We present the case of a 75 year-old man diagnosed to have a glucagonoma in 1995. He was deemed unfit for curative surgery and was managed medically including insulin therapy for control of hyperglycaemia. Over the next 7 years the patient became progressive more symptomatic due to increase in tumour size and hepatic ...

Irritable bowel syndrome (IBS) which is very common is characterized by chronic intermittent symptoms, including recurrent abdominal pain, altered frequency of defecation, stool urgency and excess flatus. Widespread symptoms associated with IBS are abnormal defecation and abdominal pain, both of which can be exacerbated by psychogenic stress. IBS is one of the stress-related bodily disorders and it has been suggested that patients with IBS may exhibit disturbances in the hypot...

Folliculostellate (FS) cells are non-hormone producing cells that represent up to 10% of the anterior pituitary gland and may mediate the response of the hypothalamic pituitary adrenal axis to inflammation. Adenosine, released during stress and inflammation, acts at A2b receptors to stimulate growth and secretion of IL-6 from a mouse FS cell line, TtT/GF. We have now extended these studies and investigated how NECA (universal adenosine receptor agonist; 10 micromolar) stimulat...

Background: In clinical practice there is considerable confusion as to whether pituitary imaging is indicated in patients presenting with a marginally elevated serum prolactin level (<1000 milliunits per litre) and no other discernible cause of hyperprolactinaemia.Objective: The aim of this study was to investigate the frequency of radiological abnormalities of the pituitary in patients presenting with marginal hyperprolactinaemia (<1000 milliunits...

Brain catecholaminergic neurotransmitters are involved in the regulation of food intake. Increased dopamin and noradrenaline release in the lateral hypothalamic area (LHA) results in inhibition of food intake whereas stimulative effects have been reported in the medial nucleus. Elevated noradrenaline levels have been shown in the hypothalamus and nucleus accumbens (NAC) of hyperphagic-hypermetabolic rats. Effects of melatonin on food intake in various species have been controv...

Background: Long-acting depot somatostatin analogues injections are useful drugs in the medical treatment of acromegaly. No previous study has assessed the value of acute octreotide suppression test in predicting responses to depot injections.Objective: The aim of this study was to investigate the value of the acute octreotide suppression test (100 micrograms subcutaneously, GH measurements hourly for 8 hours) in predicting the long-term response to long...

Leptin, which is secreted mainly by adipocytes and some other tissues including pituitary, informs the brain about the mass of adipose tissue and has an important role in energy homeostasis. We have previously shown that melatonin decreases circulating leptin levels. Whether melatonin has an effect on leptin synthesis in pituitary is currently unknown. Therefore, the aim of this study was to immunohistochemically examine the effects of pinealectomy and administration of melato...

Tumoural GH secretion in acromegaly is characterised by increased non-pulsatile (basal) release, pulse amplitude and pulse frequency. We have studied the effect of primary therapy with Sandostatin LAR on GH pulsatility in 9 patients with acromegaly who achieved disease control (mean serum GH<2ug/L) on therapy (7 males; median (range) age 67 (43-75). Data obtained were compared with 16 healthy subjects (10 males, age 50 (30-75)). Spontaneous 24-h GH secretion (20 minute samp...

The application of exogenous neurotrophins (NT) has been widely proposed as a therapeutic strategy for the recovery of regeneration in axotomised CNS neurons. Results from this approach have, however, been disappointing since limited regenerative responses are elicited, we suggest due to limited neurotrophin receptor (NTR) expression. NT exert their trophic effects by signalling through the Trk/p75 receptors. Adequate receptor expression levels must, therefore, be central to t...

Anosmin-1, a protein defective in X-linked Kallmann's syndrome (X-KS), presents a structure comprising a cysteine rich N terminus (CR), a whey acid protein (WAP) domain followed by four fibronectin-like III domains (FnIII); and its function is heparan sulphate (HS) dependent. However, anosmin-1 and HS binding affinity is unknown. Although the WAP domain belongs to a protein family demonstrating serine protease inhibitory activity, the interacting serine protease remains to be ...

Prenatal manipulations in animal models result in lifelong alterations in the stress responsivity of the hypothalamic-pituitary-adrenal axis (HPAA). While several human studies have found raised 0900h cortisol concentrations in low birthweight individuals, twenty-four hour cortisol profiles do not vary according to birthweight (a marker of adverse antenatal exposures). One explanation for this dichotomy is that 0900h cortisol concentration measured in a novel clinic setting ma...

Background: The introduction of somatostatin analogues for the treatment of acromegaly has relegated dopamine agonists, once a mainstay of treatment, down the therapeutic ladder. Dopamine agonists are, however, added to somatostatin analogues to control active disease in some patients, in an attempt to achieve biochemical control. There are no reports, however, assessing this practise.Aim: To assess the effectiveness of adding dopamine agonist therapy to...

There is increasing reliance on published consensus criteria for clinical decision-making in states of GH excess and deficiency. NICE eligibility criteria for GH treatment include a peak GH response <9 mU/L during an ITT. To determine the adequacy of GH assay performance for diagnosing GH deficiency (GHD), we have assessed the variability in 101 UKNEQAS reported results from a single sample with a value close to 9.0 mU/L. For all laboratories (n=101) median GH was 11.1 mU/L...

The melanocortin receptors (MCR), MC3R and MC4R, have established roles in feeding and pituitary function. MC5R mRNA expression has been identified at low levels in the hypothalamus. However, a role for this receptor in appetite and pituitary function remains to be elucidated. We investigated the effects of central administration of an MC5R agonist (3,3,3-triphenylpropionyl-His-D-Phe-Arg-Trp-NH2) on food intake and plasma pituitary hormone levels. We did not observe...