Endocrine Abstracts

AIM: 1) To determine GH dose requirement in GH deficient patients aged over 60 years. METHODS: The study was approved by the local Ethics Committee. Patients were started on Genotropin 0.4 units (0.13 mg)/day after baseline assessment. Serum IGF-I was repeated at 2-weekly intervals. Maintenance GH dose was achieved when serum IGF-1 was between the median and upper end of the age-related range. RESULTS: 16 patients (10 men & 6 women) were recruited. Their median (range) age...

There is increasing evidence that cytokines may play an important role in the pathogenesis of human pituitary adenomas. We have measured the production of interleukin-1 alpha from 30 cultured human pituitary adenomas and looked at the relationship of its secretion to interleukin-6 and soluble gp130. Tumours were also analysed for interleukin-2 secretion. We also used the HP75 cell line to look at the effects of varying levels of interleukin-1 on interleukin-6 secretion.<p...

Radiation-induced growth hormone neurosecretory dysfunction (GHNSD) is, primarily, the result of radiation-induced hypothalamic damage. Consequently, reduced hypothalamic growth hormone releasing hormone (GHRH) secretion results in secondary somatotroph atrophy and attenuated peak GH responses to a bolus of exogenous GHRH. For the first time we have studied the presence of GHNSD and/or somatotroph atrophy in cranially irradiated adult survivors of childhood cancer. We have uti...

Ghrelin is a novel peptide that acts on the growth hormone segratagogue receptor in the pituitary and hypothalamus. It functions as a third physiological regulator of GH secretion along with GHRH and somatostatin. In addition to the action of ghrelin on the GH axis it appears to have a role in the determination of energy homeostasis. Whilst feeding suppresses ghrelin production and fasting stimulates ghrelin release the underlying mechanisms controlling this process remain unc...

Leptin is a crucial hormone in the regulation of body weight. It is produced by adipose tissue and acts centrally decreasing appetite and increasing energy expenditure. Leptin has been shown to stimulate sympathetic nervous system activity in vitro although the physiological relevance of this remains unclear. Increased sympathetic nervous system (SNS) activity has been implicated in the pathogenesis of insulin resistance and a greatly increased cardiovascular risk. We have the...

Background: Over 90% of the blood supply to the adenohypophysis arises from hypothalamic portal vessels, in contrast to the systemic blood supply to the posterior lobe. A pre-existing, or tumour stimulated direct (non-portal) blood supply has been suggested as a possible pathogenic mechanism for prolactinoma development.Methods: 6 patients (3 microprolactinomas (mic), and 3 macroprolactinomas (mac)), and one control subject were imaged using a 3T magnet...

Background: numerous studies using a variety of quality of life (QOL) measures have shown multiple impairments in adults with growth hormone deficiency (GHD) compared to control subjects. There have been few studies however of QOL in a treated GHD population compared with healthy controls.Method: 120 adults with treated GHD ( >1 year) were given the following QOL questionnaires at annual review: SF36, Nottingham Health Profile, Disease Impact, Life F...

Introduction: Anosmin-1, which is implicated in the pathogenesis of X-linked Kallmann`s syndrome, consists of a cysteine rich region, followed by a WAP domain and 4 fibronectin type III (FN3) domains. The N-terminal region of anosmin-1, WAP and 1st FN3 domain, is highly conserved in a wide variety of species which suggests that the activity of the protein resides in these conserved segments. Difficulties in the expression of the full-length anosmin-1 by Chinese hamster ovary c...

Background: We previously demonstrated that elderly patients with GHD have increased and young GHD patients have reduced cardiac sympathovagal balance. Therefore we decided to investigate whether the relationship between age and cardiac sympathovagal balance is altered in GHD compared to healthy controls.Method: HRV, which indirectly measures cardiac sympathovagal balance, was measured in 22 untreated GHD patients (13 F; mean age 47.4 yrs; range 19-73 y...

Adeno-associated virus (AAV) has been used to express GFP in a variety of tissues. AAV has a tropism for neurones and we have been using AAV-GFP to determine the anatomical localisation of gene transfer after injection into the hypothalami of Wistar rats. The long term aim is to use this viral vector as a tool for investigating the hypothalamic control of appetite, energy expenditure and pituitary function.Male Wistar rats were anaesthetised and injecte...

The goal of this study was to determine whether injections of serotonin increase the plasma concentration of thyroxine (T4) , triiodothyronine (T3), growth hormone (GH), milk amount and constituents in the cows. sixty cows were randomly divide into 4 groups. Each group received daily injections of either saline or 1, 2, 4 milligrams serotonin per Kg for 15 days. Blood samples were collected daily on day 3 before injections untill 3 days after the last injection . Samples were ...

The consumption of a high energy (HE) diet causes a range of weight gain responses in the human population with some individuals resistant to diet induced obesity (DIO). The SD rat provides a model for DIO and this study examines the effects of HE diet on bodyweight, food intake and hypothalamic neuropeptide gene expression. 28 male out-bred SD rats (280.7±2.19g) were fed chow ad-libitum (AL) for 4 days then divided into 2 weight-matched groups: 20 rats were fed HE diet...

Insulin like growth factor-1 (IGF-1) has been shown to co-vary with renal function in a number of physiological and pathological conditions. However, this relationship and possible co-variants have not been specifically explored in untreated growth hormone deficient adults (GHDA). To examine this issue, we studied 24 GHDA subjects (14M, 10F) in the fasted state twice after obtaining consent and ethical approval. The Cockcroft and Gault equation was used to calculate creatinine...

Hypothalamic GnRH neuronal dysfunction is a frequent cause of hypogonadotrophic hypogonadism (HH) in women with secondary amenohrroea. However, the entity is poorly characterized in men, possibly due to lack of a sensitive equivalent clinical marker of the condition.A 40-year-old man presented with a 7-year history of progressive lack of energy, loss of libido, decreased sexual function, and loss of morning erections. Puberty had occurred normally and h...

Pituitary apoplexy is a rare condition caused by haemorrhage or infarction into a pituitary tumour. The majority of patients do not have any identifiable triggering event, although situations altering the blood flow to the pituitary gland and pre-existing systemic hypertension have been identified as potential causal factors.We retrospectively reviewed the presentation and outcome of 15 patients with pituitary apoplexy (8 men, 7 women; age 16-87, mean 5...

We examined the results of treatment of adult Cushing's disease by transphenoidal surgery by a single neurosurgeon (MP). Patients with Nelson's syndrome and those who previously had received treatment for Cushing's by a different surgeon were excluded. We reviewed the pituitary database and patient records for all patients operated between 1988 and 2000 with clear pre-operative evidence of Cushing's disease. 117 patients had clear evidence of a pituitary source of excess ACTH....

We reported that leptin mRNA is developmentally regulated and hypothesized that local leptin expression is important for the maturation of the hypothalamic-pituitary system. Pituitary leptin mRNA levels were down-regulated in early postnatal male and female rats. We now show that pituitary leptin protein content and expression of the long (OBRb) and short (OBRa) leptin receptor isoforms in the pituitary and hypothalamus also undergo age-related changes. Tissue wa...

Survival figures following the treatment of brain tumours continue to improve. Patients receiving cranial radiotherapy (XRT) frequently suffer a progressive loss of anterior pituitary function secondary to radiation damage to the hypothalamic pituitary axis (HPA), therefore long-term follow up is required. The time frame of radiation damage to the HPA is not known. There is also a suggestion from animal data that the HPA is more sensitive to damage by radiation when treated at...

Background: Weight gain is underrecognised in patients with hypothalamic damage and the prevalence and mechanisms are poorly defined. The aim of this study was to define the diagnoses and endocrine characteristics associated with weight gain.Subjects and methods: A retrospective study of 48 patients (25 female) mean (SD) age 45.3yrs (9.8).They included 22 patients with primary hypothalamic lesions (craniopharyngiomas, Rathke's cysts and other tumours)[g...

OBJECTIVE Induction of anaesthesia and surgical stress, factors known to trigger catecholamine release from phaeochromocytomas, are believed to result in elevated levels in the postoperative period even in the absence of such tumours, and biochemical screening is usually deferred for two or more weeks following surgery. The aim of this study was to determine patterns of peri-operative urinary catecholamine excretion in otherwise healthy subjects undergoing a single type of maj...

The goal of this study was to determine whether injections of bombesin increase the plasma concentration of thyroxine (T4) , triiodothyronine (T3), growth hormone (GH), milk amount and constituents in the cows. sixty cows were randomly divide into 4 groups. Each group received daily injections of either saline or 1, 2, 4 milligrams bombesinper kilogram for 15 days. Blood samples were collected daily on day 3 before injections untill 3 days after the last injection . Samples we...

The hypothalamic pituitary adrenal (HPA) axis is the major regulator of stress and inflammation via the secretion of anti-inflammatory corticosteroids. This suggests an important bidirectional flow of information between the endocrine and immune systems. A critical component of the inflammatory response is the complement cascade in which anaphylatoxins C3a, C4a and C5a are released.In this report we used colocalisation immunohistochemistry to show detai...

Introduction: Ageing is associated with a decrease in activity of the growth hormone / IGF-1 axis. However, there is little normative data for serum IGF-I levels in the very elderly and the relationship of IGF-1 levels to muscle function and physical performance in geriatric inpatients has not been fully explored. We studied elderly patients rehabilitating after proximal femoral fracture (PFF), hypothesising that patients with lower circulating IGF-1 levels would have poorer p...

Patients with acromegaly treated with medical therapy intermittently discontinue therapy to allow assessment of underlying disease activity. This is particularly so in patients treated with pituitary irradiation. Typical 'washout' times include 5 weeks for bromocriptine and 2 weeks for short-acting sc octreotide; longer periods are required for cabergoline and slow-release somatostatin analogues. Pegvisomant is a novel medical therapy for acromegaly that functions as a GH rece...

Transsphenoidal surgery (TSS) is the most common first-line treatment for Cushing's disease (CD). We have examined the outcome of this intervention to identify pre-operative clinical factors that predict good surgical outcome and to determine the risk of adverse events.We performed a case-notes review of 30 consecutive patients, 20 (67%) female, treated by a single surgeon over a 14-year period. The mean (SE) age was 34.2 (2.1) years and median (range) ...

It is well established that catecholamines have potent actions on adrenocortical function and steroidogenesis in different species. The effect of these substances on steroid production of the human adrenal cell line H295R is the subject of this study. H295R is the first adrenocortical cell line capable of secreting the normal range of adrenal steroid products (i.e. mineralocorticoids, glucocorticoids and adrenal androgens) and since free of chromaffin cells, it appears to be a...

Vasoactive intestinal peptide (VIP) and Neuropeptide Y (NPY) are well established paracrine regulators of adrenal function. These neuropeptides have recently been immunolocalised to the capsule and zona glomerulosa region of the adrenal cortex, where they play a role in regulating steroidogenesis and adrenal blood flow. Neural mediation of compensatory adrenal growth following unilateral adrenalectomy and stimulation of proliferation and vascular hypertrophy in vascular smooth...

The number of patients treated for malignant disease in childhood surviving into adulthood is increasing, but success is tempered by long-term side-effects of chemotherapy and radiotherapy; 40% develop one or more endocrinopathy. ALL is a common childhood malignancy treated with chemotherapy and cranial irradiation. The latter causes anterior pituitary hormone deficiencies, most frequently GH deficiency.We have determined GH status in 13 patients treate...

Due to the infrequency of pituitary apoplexy, there are no robust evidence-based guidelines for optimum care of these patients. The key controversy surrounds the role of acute neurosurgical intervention. Over recent years we have adopted a relatively conservative approach and the aim of this study was to determine whether this 'non-intervention' affected long-term outcome in a recent cohort of patients. 19 patients (8 female) presented between 1994-2001. Mean age at diagnosis ...

Prolactin releasing peptide (PrRP) is reported to decrease plasma growth hormone (GH) levels in the rat but increase GH release from human pituitary cells. A barbiturate anaesthetised model was used in the rat studies (where basal plasma growth hormone is elevated) and in humans the GH stimulatory effects were of a small magnitude and seen only in foetal or tumourous pituitary cells. Our studies have examined the role of PrRP in freely moving male rats without the influence of...

Studies have demonstrated an increased mortality in patients with acromegaly. The major cause of premature death was cardiovascular disease. Cardiovascular mortality was increased in patients with high levels of growth hormone (GH). Somatostatin analogues, such as octreotide, are effective in relieving the symptoms of acromegaly and supressing GH hypersecretion. Long acting preparations, such as Sandostatin-LAR, offer theoretical advantages over SC preparations, such as improv...