bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pituitary macroadenomas associated with hyperprolactinaemia: immunocytochemical and in‐situ hybridization studies
Authors: McNicol A. M. , Walker E. , Farquharson M. A. , Teesdale G. M. 
Published: March 2008

Summary. objective We have assessed whether in‐situ hybridization for prolactin messenger RNA (mRNA) provides additional Information for the classification of pituitary macroadenomas associated with hyperproiactinaemla.design in‐situ hybridization for PRL mRNA was performed on surgical biopsies of pituitary adenomas and the results correlated with serum PRL levels and PRL immunoreactivity.patients Twenty‐one patients (11 men, 10 women) were included; five had normal serum PRL levels, 11 mild hyperprolactinaemia (< 3000 mU/I) and five marked hyperprolactinaemia (> 3000 mU/I).measurementsImmunocytochemistry for PRL and in‐situ hybridization for PRL mRNA were performed on surgical biopsies.results Immunoreactivity for PRL was detected In tumours from all patients with serum PRL > 3000 mU/I and in one of 11 patients with mild hyperprolactinaemla. Positive signal for PRL mRNA was detected in four of five immunopositive cases studied, in a further two cases with mild hyperprolactinaemia, and in one tumour associated with normal serum PRL level.conclusionsIn‐situ hybridization provides evidence of PRL gene activation in the absence of immunoreactivity for prolactin. This may reflect low levels of hormone storage or defective translation of the mRNA.
Correlation of plasma insulin and insulin‐like growth factor‐I with indices of androgen transport and metabolism in women with polycystic ovary syndrome
Authors: Sharp P. S. , Kiddy D. S. , Reed M. J. , Anyaoku V. , Johnston D. G. , Franks S. 
Published: March 2008

Summary. objective Polycystic ovary syndrome (PCOS) Is said to be associated with hyperinsulinaemia. Insulin stimulates androgen production by ovarian tissue in vitro and previous studies have identified a positive correlation of Insulin with androstenedione. The aim of the present study was to discover whether insulin levels correlate with clinical presentation and with markers of androgen trans‐port and metabolism In women with PCOS.designWithin‐group analysis of clinical and biochemical characteristics of a consecutive series of women with PCOS, focusing on correlations of plasma insulin with clinical presentation and androgens. Insulin levels were also compared with a control group of normal women.patients Forty‐seven women who presented with hirsutlsm, cycle abnormalities or both, with ultrasound proven PCOS, were recruited. Mean age was 26.6±0.7 years (mean±SEM), BMI 27.3±1.2 kgtm2.measurements Plasma Insulin levels were measured at 30‐minute intervals for 3 hours following a 75 g glucose load. Blood was also taken for measurement of testosterone (T), androstenedione (A), free testosterone (f T), sex hormone binding globulin (SHBG) and Insulin‐like growth factor‐i (IGF‐I). Androsterone glucoronide (AG), a marker of peripheral androgen metabolism, was also measured. RESULTS Neither basal Insulin nor the sum of Insulin measurements during the glucose tolerance test (sumINS) in women with PCOS were significantly different from a control group with normal ovaries. Within the PCOS group, basal insulin was greater in women with Irregular cycles or amenorrhoea than In those with regular ovule‐tory menses (8.0± 1.1 vs 3.1 ± 1.5 mU/I, P < 0.01) despite similarly raised androgen levels. Both basal Insulin and sumINS correlated with BMI In women with PCO (r=0.37, P < 0.05 and r= 0.64, P < 0.01 respectively) but not in controls. There was no significant correlation between insulin or IGF‐I levels and T, A or AG despite a positive correlation of AG (but no other androgen) with BMI. SHBG showed an Inverse correlation and I T correlated positively with sumINS (r= ‐0.51, P < 0.01; r=0.39, P < 0.05). Regression analysis of each of the androgens on the other variables demonstrated no significant relationship between insulin and androgens.conclusions These data suggest that, in vivo, the major effect of insulin on androgen secretion is mediated by changes In SHBG rather than by direct stimulation of ovarian androgen production. Higher Insulin concentrations In anovulatory compared with ovulatory women with hyperandrogenaemia may indicate that Insulin resistance In the ovary contributes to the mechanism of anovulatio in PCOS.
Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man
Authors: Witten G. A. , Stewart D. E. , Graves M. P. , Ellis M. J. , Evans M. J. , Wells J. E. , Donald R. A. , Espiner E. A. 
Published: March 2008

Summary. objective To evaluate the hypothalamo‐pitultary‐adrenal (HPA) response to both mild and Intense exercise.design Maximum oxygen consumption (Vo2max.) was Initially determined. Exercise to 20% (mild) and 90% (Intense) Vo2max. was undertaken in random order. Subjects were exercised over a 5‐minute period to the required level of Intensity, which was maintained for a further 10 minutes.subjects Six trained male athletes.measurements Brachial vein blood was sampled before and at 5‐minute intervals during and after exercise and assayed for plasma cortisol, ACTH, arginine vasopressin (AVP), corticotrophin releasing factor (CRF), sodium and lactate levels. Haemoglobin and haematocrit were measured before and at the end of exercise. Heart rate was monitored continuously and blood pressure measured whenever blood was sampled before and after exercise.results Maximum heart rate was 184.2 and 82.5 (mean ± SEM) beats per minute at 90 and 20% Vo2max. respectively. Plasma volume fell by 8.7 ± 2.4% with intense exercise. Significant increases in plasma concentrations of AVP, ACTH and conisol, but not CRF, occurred during intense exercise. Plasma sodium concentration, which Increased during intense but not mild exercise, peaked at 10 minutes after the onset of exercise and preceded the rise in plasma AVP. The AVP peak clearly preceded the ACTH peak in two subjects and occurred synchronously with it in three subjects.conclusion These results Indicate that although significant HPA activation occurs during Intense exercise, CRF does not appear to play a major role In mediating the ACTH response to an acute episode of vigorous exercise in man. AVP may be more important In this regard.
Ketoconazole treatment in Cushing's syndrome: experience in 34 patients
Authors: Sonino Nicoletta , Boscaro Marco , Paoletta Agostino , Mantero Franco , Zillotto Donato 
Published: March 2008

Summary. objective Ketoconazole treatment of Cushing's syndrome has been reported in single cases and a few small groups of 5–8 patients. We report our experience in 34 patients.design Clinical study, with pretreatment and post‐treatment evaluations.patients Out of 67 patients with Cushing's syndrome admitted during the last 6 years, 34 (28 females/six males; age range 14–67 years) received ketoconazole as a palliative treatment due to severe clinical conditions or management of the disease while awaiting results of definitive therapy.measurements Urinary cortisol, plasma cortisol and ACTH, and routine chemistry were measured every week for 4 weeks, and then once a month.results Comparing the last values (mean±SEM) during treatment with baseline, urinary cortisol decreased from 1296.176 to 270.69 nmol/d (n=34; p=<.001); plasma cortisol decreased from 672 . 31 to 549 ± 35 nmol/1 (n= 34; p < 0.001). For patients with pituitary‐dependent Cushing's syndrome, urinary cortisol decreased from 1073.126 to 200.21 nmol/d (n=28; p<0.001) while plasma ACTH changed from 12.5±1.3 to 11.3±0.8 pmol/1 (n=26; not significant). Twelve patients were treated for more than 6 months, and those with pituitary‐dependent disease all received pituitary radiation therapy, except the two who eventually escaped pharmacological control. One additional patient with adrenal carcinoma and one with ectopic ACTH syndrome showed lack of control of urinary cortisol levels. Ketoconazole was withdrawn within the first week In two patients for allergic reaction and acute liver toxicity. Other side‐effects Included: asymptomatic liver function abnormalities In three patients; gastrointestinal symptoms in four; worsening of gynaecomastia In one. Rapid clinical Improvement was observed together with the normalization of urinary cortisol levels, with regression of symptoms such as diabetes mellitus, hypertension, hypokalaemia, and restoration of well being.conclusions These data confirm that ketoconazole is valuable In the management of hypercortlsolism, provided that patients are closely watched to exclude those who may develop liver toxicity and to prevent the occurrence of adrenal Insufficiency.
The interaction of growth hormone releasing hormone and somatostatin in the generation of a GH pulse in man
Authors: Hindmarsh P. C. , Brain C. E. , Robinson I. C. A. F. , Matthews D. R. , Brook C. G. D. 
Published: March 2008

Summary. objective To study the regulation of the growth hormone (GH) response to growth hormone releasing hormone (GHRH) in the presence or absence of somatostatin pretreatment.design Seven healthy adult male volunteers of normal height and weight and aged between 19 and 29 years underwent four separate studies (each containing three cycles In one day) In random order. The studies were separated from each other by at least a week. On day 1, three consecutive cycles (between 0800 and 2000 hours) consisted each of a saline infusion for 3 hours which was stopped prior to a bolus Injection of saline and followed by 60 minutes of more intensive blood sampling.On day 2, the bolus Injections were of GHRH given after saline infusion. On days 3 and 4 somatostatin Infusions were administered instead of saline over the 3‐hour periods followed by bolus injections of saline or GHRH respectively.In all studies, samples were collected for the measurement of serum GH concentration at 15‐minute Intervals from time 0 to 180 minutes and then at 5‐minute Intervals for a further 60 minutes, this cycle being repeated three times.measurements Serum GH concentrations were analysed by serial array averaging.results Prompt release of GH was observed In response to GHRH given against a saline background (day 2, cycle 1) (mean at 60 minutes 49.2±14.7 mU/1) but the responses observed during the second and third cycles were attenuated (mean at 60 minutes 17.2±4.0 mU/1; p=0025). GH release between somatostatin infusions (somatostatin withdrawal; day 3) occurred twice as often as that observed during saline Infusions (62% day 3: 29% day 1). The response, although qualitatively similar to that Induced by GHRH, was reduced in amplitude and the time of onset variable (5–45 minutes).On day 4, the administration of GHRH as a bolus injection combined with somatostatin withdrawal led to consistent and repeatable GH responses (mean at 60 minutes, cycle 1, 39.7±10.8 mU/1; cycles 2 and 3, 37.4±9.4 mU/1) which were similar to those observed with GHRH alone (day 2, cycle 1) (mean 39.7±10.8 mU/1) (p=NS).conclusions These data suggest that endogenous somatostatin secretion is important In determining the ability of the somatotroph to respond to repeated growth hormone releasing hormone stimulation and that for regular GH pulse generation a close Interplay between growth hormone releasing hormone and somatostatin is required.
The effect of a highly specific serotonin agonist on osmoregulated vasopressin secretion in healthy man
Authors: Faull C. M. , Rooke P. , Baylis P. H. 
Published: March 2008

Summary. objective To explore a possible Interaction of the serotonin neurotransmitter system and posterior pituitary function, we have looked at the effect of fluoxetine treatment on osmoregulated vasopressin secretion in normal men in two placebo controlled studies.design in each study subjects took in random order for 7 days one capsule daily of placebo or 40 mg fluoxetine. On the 8th day subjects underwent assessment. Study 1 A hypo‐osmotic stimulus of an oral water load of 20 ml/kg. Study 2 A hyperosmotic stimulus of intravenous infusion of 5% (855 mmol/l) saline at 0.06 ml/kg/min for 120 minutes.patients Normal, healthy male volunteers. Study 1, 9; Study 2, 10.measurements in both studies regular measures of plasma osmolality, sodium and vasopressin were made. In Study 1 urine osmolality was measured together with urine volume at set time points and an accumulative measure of percentage of water load excreted. Free water clearance was calculated. In Study 2 the relationship of plasma vasopressin to change in plasma osmolality was calculated for each subject by linear regression analysis. RESULTS Serotonin agonism had no effect on baseline measurements in either study. Study 1 After 4 hours subjects excreted 95 and 99% of the water load after placebo and fluoxetine respectively (P= 0.407). There was no effect of fluoxetine compared to placebo on the pattern or extent of change of plasma osmolality (nadir 285.9±1.4 mosm/kg placebo, 283.1±1.1 mosm/kg fluoxetine, P= 0.145) or on free water clearance or maximum urine dilution after oral water loading. Plasma vasopressin suppressed to a minimum concentration after both treatments in response to hypo‐osmolality 0.510±1 pmol/l (placebo), 0.3±0.01 pmol/l (fluoxetine), P= 0.195. Study 2 Fluoxetine had no significant effect on the sensitivity of vasopressin release to change in plasma osmolality (0.33±0.06 pmol/l per mosm/kg placebo, 0.36±0.06 pmol/l per mosm/kg fluoxetine, P= 0.347). Nor was there a significant effect on the theoretical osmotic threshold for release of vasopressin (287.011.21 mosm/kg placebo, 286.9±1.09 mosm/kg fluoxetine, P= 0.700).conclusionWe have found no evidence of a physiologically relevant effect of serotonin agonism on osmoregulated vasopressin release, or on the ability of normal man to excrete a water load. The possible reasons for this contrast to animal work are discussed.
Correlations between mean LH levels and LH pulse characteristics: differences between normal and anovulatory women
Authors: Bennet A. , Lacaze J. CI. , Caron Ph. , Berrada R. , Barbe P. , Louvet J. P. 
Published: March 2008

Summary. objective Since LH secretion occurs as a series of pulses, relationships between mean LH levels and LH pulse characteristics are to be expected. The aim of this study was to determine whether such relationships are similar in normal women and anovulatory patients.design We studied the correlations between mean LH levels and the products amplitude X frequency and area X frequency of LH pulses in normal women and In patients with disorders of ovulation. Blood samples were taken from each subject every 10 minutes during 6 hours on the 8th day after the last menses.patients The patients were divided into three groups: patients with polycystic ovary syndrome (n= 11), patients with idiopathic anovulatlon (n= 14) and patients with short luteal phase (n=13). Their results were compared to those of 12 normal women.measurementsLH was evaluated with an Immunoradlometric assay. LH data were analysed with a 3 standard deviation threshold criterion for significant peaks, and with cluster analysis algorithm using 1, 2.5 and 5% false positive error rates and ‘optimal parameters’ (which give less than 5% false positive and false negative error rates in LH male data).results Highly significant correlations between amplitude x frequency, area x frequency and mean LH were found In normals and patients with short luteal phase; no significant correlation was found in patients with polycystic ovary syndrome, while significant correlations were found in patients with idiopathic anovulatlon only with some of our criteria for peak detection.conclusion The differences that we found between the groups suggest that when commonly used methods are employed to determine LH pulse characteristics, most of the significant LH pulses are taken Into account in normals and patients with short luteal phase, but not in anovulatory patients, especially in patients with poiycystic ovary syndrome. This method using two correlations appears to be a simple and useful way to show the differences In the mechanisms by which mean LH levels are achieved In normal subjects and patients.
The effect of thyroxine on small intestinal motility in the elderly
Authors: Rahman Q. , Haboubi N. Y. , Hudson P. R. , Lee G. S. , Shah I. U. 
Published: March 2008

Summary.objectiveTo study the effects of thyroxine on orocaecal transit time In a group of elderly hypothyroid patients on long‐term thyroxine replacement therapy.designMeasurement of the effect of withdrawal and subsequent replacement of thyroxine replacement therapy on orocaecal transit time.patientsFifteen elderly, previously hypothyroid patients on full replacement therapy with oral thyroxine were studied. There were 11 females and four males, aged 60–94 years (median 78 years) receiving initially 50–200μg of oral thyroxine daily (median 100μg).measurementsSerum TSH and FT4 were measured by radioimmunoassay and orocaecal transit time assessed using a lactulose hydrogen breath test. These tests were repeated 7 days after withdrawal of thyroxine replacement and again 7 days after subsequent reinstatement of therapy.resultsOn withdrawal of therapy, the median transit time Increased from 75.0 to 135 minutes (P< 0.01), the median TSH Increased from 1.8 to 2.3 mU/l (P= NS) and the median FT4 decreased from 13.7 to 10.6 pmol/l (P< 0.01). On reinstatement of therapy, the median transit time decreased to 95 minutes (P= NS), the median TSH decreased to 1.1 mU/I (P= NS) and the median FT4 increased to 14.1 pmol/l (P< 0.01).conclusionsThese findings demonstrate the sensitivity of the small bowel to changes in thyroid hormone status and suggest that constipation arising as a result of this hypomotility may well be an early physical manifestation of hypothyroidism.
Effects of growth hormone administration on dehydroepiandrosterone sulphate, androstenedione, testosterone and Cortisol metabolism during nutritional repletion
Authors: Ziegler Thomas R. , Barbieri Robert L. , Young Lorraine S. , Ferrari‐Baliviera Elizabetta , Wilmore Douglas W. 
Published: March 2008

SummaryThis study evaluated whether pharmacological doses of recombinant human growth hormone (hGH) influences androgen or Cortisol metabolism during nutritional repletion following prolonged illness. Stable hospitalized adults (three male, seven female) receiving constant calorie and protein intake were studied. An initial control week was followed by a treatment period during which hGH (10 mg/day s.c.) was administered daily. Prior to hGH treatment, serum and 24‐h urinary concentrations of dehydroepiandrosterone sulphate (DS) were below the normal range; serum androstenedione and testosterone concentrations were within the lower limit of normal. In contrast, serum Cortisol (F) and 24‐h urinary F excretion were normal. During hGH treatment, nitrogen balance became positive and plasma insulin‐like growth factor I (IGF‐I) concentrations rose five to seven‐fold. However, serum DS, androstenedione, testosterone and F, and urinary F excretion did not change, while 24‐h urinary DS excretion fell significantly. Growth hormone administration markedly stimulated protein anabolism but did not increase the low concentrations of circulating androgens or alter the disassociation between adrenal androgen and F release in stable hospitalized males and females. Thus, hGH does not appear to function as a cortical adrenal androgen stimulating hormone (CASH) or regulate adrenal Cortisol or gonadal androgen release in this clinical setting.
A retrospective audit of the combined pituitary function test, using the insulin stress test, TRH and GnRH in a district laboratory
Authors: Pavord Sue R. , Girach Anlz , Price David E. , Absalom Steve R. , Falconer‐Smith James , Hewlett Trevor A. 
Published: March 2008

SUMMARY objective To assess the value of the combined insulin stress test (IST), thyrotrophin‐releaslng hormone (TRH) and gonadotrophin hormone‐releasing hormone (GnRH) tests design A retrospective audit of 232 such tests performed between 1980 and 1989 inclusive patients One hundred and ninety‐seven patients with known or suspected pituitary disease measurements IST, TRH and GnRH responses were retrieved from laboratory records. Case notes were surveyed for clinical data and additional results results A basal serum cortisol level of > 100 nmol/l (or > 200 nmol/l in patients who had recently received glucocorticoid replacement therapy) accurately predicted a subnormal response to hypoglycaemla. All patients with a basal cortisol level of >400 nmol/l, except those who had recently received steroids, showed a normal cortisol response. In retrospect, by consideration of such basal values, 55% of ISTs could have been avoided if the only aim was to assess cortisol reserve. A deficient growth hormone (GH) response to hypoglycaemia was, however, common In patients with a normal cortisol response. Two‐thirds of patients with GH deficiency would have been missed If an IST had been avoided on the basis either of basal cortisol levels alone, or of cortisol responses to an alternative test which did not test GH reserve. There was poor agreement between the pituitary response to TRH and GnRH and basal levels of thyroxlne and gonadotrophins respectively, suggesting that these releasing hormone tests are misleading. conclusions The IST provides information regarding pituitary function not provided by other tests of the hypothalamlc‐pltuitary‐adrenal axis, so that the choice between the IST and alternative tests must depend on a critical assessment of what Information is required. Routine TRH and GnRH testing appears to yield little Information of practical clinical value
Pituitary imaging using a labelled somatostatin analogue in acromegaly
Authors: Ur E. , Mather S. J. , Bomanji J. , Ellison D. , Britton K. E. , Grossman A. B. , Wass J. A. H. , Besser G. M. 
Published: March 2008

SUMMARY objective A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We have looked at the use of an 123I‐labelled Tyr3‐octreotlde analogue of somatostatin In the visualization and functional characterization of growth hormone‐secreting pituitary adenomas. patients Fifteen patients with biochemically‐proven acromegaly were scanned using this agent. In eight of these we also assessed acute GH responses to octreotide in order to correlate these responses with tumour uptake characteristics measures Planar and single‐photon‐emlsslon computerized tomographic (SPECT) images of the head were obtained using a gamma‐camera at 10 minutes, and 4 and 24 hours, after injection of the radiopharmaceutical. Blood for serum GH was sampled for 12 hours after administration of a single dose of 100 μ g octreotide. results Twelve of the acromegalic subjects showed significant uptake of the radiopharmaceutical in the pituitary fossa. Of the eight patients In whom we assessed acute GH responses, five demonstrated a significant fall in GH in response to octreotide. These subjects also showed positive uptake in the pituitary on scanning. The three patients who had no fall in GH had no uptake on scanning conclusions Uptake of 123I‐labelled Tyr3‐octreotide in the pituitary fossa appears to correlate closely with the presence of a therapeutic response to octreotide.