bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and determinants of left ventricular hypertrophy in acromegaly: impact of different methods of indexing left ventricular mass
Authors: Vitale Giovanni , Galderisi Maurizio , Pivonello Rosario , Spinelli Letizia , Ciccarelli Antonio , De Divitiis Oreste , Lombardi Gaetano , Colao Annamaria 
Published: December 2004

Summarybackground  Left ventricular hypertrophy (LVH) is the most common cardiac abnormality in acromegaly. Left ventricular mass (LVM) is an important parameter measured to detect LVH, but the relationship with body size should be considered by correcting LVM to body surface area (BSA), height or height2·7. All trials concerning acromegaly have detected LVH on the basis of LVM indexed for BSA, but have been criticized for disregarding the effects of obesity.patients and measurements  97 patients with active acromegaly and a control group of 97 nonacromegalic subjects, were compared for the prevalence of LVH, calculated with different corrections of LVM for BSA, height and height2·7. In addition, we evaluated determinants of LVH in acromegalic group.results  In controls, the prevalence of LVH, determined by correcting LVM for BSA (10·3%) was significantly lower than correcting by LVM/height (21·6%, P = 0·05) and LVM/height2·7 (33%, P < 0·0001). Similarly, in the acromegalic population the prevalence of LVH was significantly higher when measured by LVM/height (86·6%) or LVM/height2·7 (89·7%), than by LVM/BSA (67%) (P = 0·002 and P < 0·0001, respectively). A lower prevalence of LVH detected by LVM/BSA than LVM/height and LVM/height2·7 has been observed in an acromegalic overweight group, while in patients with normal weight there was no significant differences using different corrections. In acromegalic patients with disease duration of ≤ 10 years the prevalence of LVH by correcting LVM for height2·7 was higher than when correcting for BSA. No difference in the prevalence of LVH determined by different corrections was observed in patients with disease duration > 10 years. By separate multiple regression analyses systolic blood pressure was the only independent determinant of LVM/BSA or LVM/height, while systolic blood pressure and GH levels were both predictors of LVM/height2·7.conclusions  LVM indexed for height2·7 appears to be the most appropriate method to identify LVH in acromegaly, particularly in overweight patients and those with shorter disease duration.
Efficacy of Sandostatin® LAR® (long‐acting somatostatin analogue) is similar in patients with untreated acromegaly and in those previously treated with surgery and/or radiotherapy
Authors: Ayuk John , Stewart Susan E. , Stewart Paul M. , Sheppard Michael C. ,   the European Sandostatin LAR Group
Published: December 2004

Summarybackground and objectives  Somatostatin analogues have been used as an adjunct to surgery and radiotherapy in the treatment of acromegaly for over 15 years, but debate surrounds their use as primary therapy. Newman suggested that octreotide was equally effective as primary or adjuvant therapy, but the effects of previous surgery/radiotherapy may have led to a preselection bias. In an attempt to eliminate this bias, the efficacy of the depot somatostatin analogue Sandostatin® LAR® as primary and adjuvant therapy has been assessed using GH and IGF‐I levels at diagnosis as baseline values.design  We retrospectively analysed the GH and IGF‐I data from a large multicentre study in which patients’ biochemical response to treatment with the depot somatostatin analogue Sandostatin LAR as primary and adjuvant therapy was assessed. We used GH and IGF‐I levels at diagnosis as baseline values to eliminate any preselection bias.patients and results  In 91 patients (42 male) studied, mean serum GH fell from 36·2 ± 3·3 µg/l (SEM) at diagnosis to 2·2 ± 0·2 µg/l after 48 weeks of treatment (P < 0·0001). In the primary (n = 34) and adjuvant (n = 57) therapy groups, mean GH fell from 30·7 ± 5·7 to 2·6 ± 0·4 µg/l (P < 0·0001) and from 39·5 ± 4·1 to 2·0 ± 0·2 µg/l (P < 0·0001), respectively. Sixty‐two percent of patients in the primary therapy group and 70% in the adjuvant therapy group achieved GH < 2 µg/l. Serum IGF‐I levels were available in 67 patients (34 male). In the primary therapy group (n = 25) mean IGF‐I fell from 764 ± 68 to 414 ± 31 µg/l (P < 0·0001) at 48 weeks. In the adjuvant therapy group (n = 42) mean IGF‐I was 666 ± 50 µg/l, falling to 384 ± 30 µg/l (P < 0·0001) at 48 weeks. 72% of patients achieved normal age‐related IGF‐I‐values. There were no statistically significant differences in GH or IGF‐I levels between the primary and adjuvant therapy groups at diagnosis, pre Sandostatin LAR or after 48 weeks of treatment.conclusion  This retrospective study demonstrates that in a group of patients with similar diagnostic GH and IGF‐I levels, Sandostatin LAR was equally effective as primary therapy in acromegalic patients as in patients previously treated with surgery and/or radiotherapy.
Ghrelin secretion is modulated in a nutrient‐ and gender‐specific manner
Authors: Greenman Yona , Golani Nehama , Gilad Susan , Yaron Mariana , Limor Rona , Stern Naftali 
Published: December 2004

Summarybackground  Ghrelin is a potent GH secretagogue that also plays an important role in appetite and weight regulation. Ghrelin increases hunger and food intake, and its levels decrease after a standard meal or glucose.objective  To examine the effects of standard oral glucose, lipid and protein loads on ghrelin levels, investigating the possibility that these responses may be modulated by several anthropometric and metabolic factors.subjects and methods  There were 24 adult nondiabetic subjects (13 men/11 women; mean age 55·3 ± 2·9 years, range 26–74 years). Each participant underwent one or more of the following nutrient loads: (i) a standard oral glucose (75 g) load (n = 18); (ii) an oral lipid load (40 g, with 24 g saturated fat; n = 13); (iii) an oral protein load (40 g; n = 11).results  Fasting ghrelin levels were negatively related to body mass index (BMI; r =−0·47; P = 0·02), waist circumference (r = −0·58; P = 0·0028), waist/hip ratio (r = −0·56; P = 0·0046), fasting insulin (r = −0·44, P = 0·03), and homeostasis model assessment insulin resistance index (HOMA‐R; r = −0·43, P = 0·034). Glucose load induced a decrease in ghrelin levels (P < 0·0001), and this response was modulated by sex (P < 0·0001), in that levels were significantly higher in females. The presence of obesity affected ghrelin response to glucose (< 0·0217), in that log‐transformed ghrelin levels started to increase back to baseline after its initial decline earlier in obese than in lean subjects. Ghrelin levels after a glucose load were lower over time in subjects with more pronounced insulin resistance (P < 0·0001). Similarly, ghrelin levels decreased significantly following the lipid meal (P = 0·035), and were modulated by HOMA‐R (P = 0·027) and gender (P = 0·029). Protein did not affect ghrelin levels.conclusions  This study demonstrates that ghrelin levels respond in a different manner to glucose, lipid and protein loads, and are subject to modulation according to gender, obesity and insulin sensitivity.
Reduced p18INK4c, p21CIP1/WAF1 and p27KIP1 mRNA levels in tumours of primary and secondary hyperparathyroidism
Authors: Buchwald Pamela Correa , Åkerström Göran , Westin Gunnar 
Published: December 2004

Summaryobjective  Hyperparathyroidism (HPT) refers to states of excessive production of parathyroid hormone (PTH). The eukaryotic cell cycle is driven forward by cyclins and their cyclin‐dependent kinase (CDK) partners. Cyclin‐dependent kinase inhibitors (CKIs), which generally inhibit cell cycle progression, modulate the activity of cyclin–CDK complexes.design  In order to quantify the expression of the CKI genes p18, p21, and p27 semiquantitative RT–PCR with mRNA specific‐primers was performed on four normal parathyroid biopsies, 31 parathyroid adenomas of primary HPT and 13 hyperplastic glands from uraemic patients with secondary HPT.patients  Parathyroid adenomas and secondary hyperplastic glands were obtained from 31 and 13 randomly selected patients undergoing parathyroidectomy in the clinical routine, respectively. Four normal parathyroid gland biopsies were obtained at surgery for pHPT or from normocalcemic patients undergoing thyroidectomy for goitre.results  The relative p27 expression (p27/GAPDH) was significantly reduced in parathyroid adenomas compared to normal parathyroid gland biopsies. Furthermore, 42% and 53% of the parathyroid adenomas displayed undetectable p18 and p21 expression levels, respectively. All 13 adenomas that lacked p18 expression showed undetectable p21 expression. The p18 expression was significantly lower in tumours of uraemic sHPT as compared to normal parathyroids and an undetectable expression level was observed for p21 and p27 in 61% and 53%, respectively.conclusion  Parathyroid adenomas and secondary hyperplastic glands exhibit aberrant reduced expression of the CKIs p18, p21, and p27. This suggests that deranged collaboration of different CKIs may contribute to the development of both primary and secondary HPT.
Unchanged fasting and postprandial adiponectin levels following a 4‐day caloric restriction in young healthy men
Authors: Imbeault Pascal , Pomerleau Marjorie , Harper Mary Ellen , Doucet Éric 
Published: December 2004

Summaryobjective  Adiponectin is an adipocyte‐secreted protein that has been shown to promote fat oxidation and insulin sensitivity in animals. Whether acute energy restriction is associated with modulation of adiponectin in humans remains largely unknown. The purpose of this study was to examine the effects of a short‐term caloric restriction on fasting and postprandial adiponectin levels in young healthy men.research design and methods  Fifteen young healthy men were subjected to a 4‐day energy restricted diet (−800 kcal/day). Before and after the intervention, anthropometric measurements, fasting and postprandial glucose, insulin and adiponectin were measured at 0, 30 and 60 min after a fixed breakfast.results While fat mass remained stable, minor but significant changes in weight were observed after the 4‐day energy‐restricted diet. Glucose and insulin levels increased postprandially, and patterns did not differ before and after the intervention. Fasting levels of adiponectin remained unchanged after the energy restriction, and postprandial levels were not significantly different from fasting levels either before, or after, the intervention.conclusions Fasting and postprandial adiponectin levels are not acutely modulated by a short‐term energy restriction in young healthy men.
The effects of GH replacement in adult GH‐deficient patients: changes in body composition without concomitant changes in the adipokines and insulin resistance
Authors: Hana Vaclav , Silha Josef V. , Justova Vlasta , Lacinova Zdena , Stepan Jan J. , Murphy Liam J. 
Published: December 2004

Summarybackground  Growth hormone deficiency (GHD) in adult life has been associated with increased central adiposity, decreased insulin sensitivity, dyslipidaemia and increased risk of cardiovascular disease. The effects of GH replacement on adiponectin and resistin, adipokines which have a role in modulating insulin sensitivity have not been previously reported.aim  To examine the effects of GH replacement on adipokine levels and insulin resistance in GHD patients.design  Seventeen adult GHD patients were examined at baseline and after 1 year of treatment with recombinant human GH (mean dose 0·31 mg/day, range 0·13–0·67 mg/day).results  GH replacement significantly increased IGF‐I levels. The mean IGF‐I SD score increased from − 1·98 at baseline to 0·76 at study end. GH replacement was associated with a significant reduction in percentage body fat (34·11 ± 1·33 vs. 30·65 ± 1·27%, P < 0·0005) and a significant increase in lean body mass (63·57 ± 1·24 vs. 66·96 ± 1·18%, P < 0·0004), before and after treatment, respectively. Surprisingly, there was no effect of GH replacement on the plasma levels of leptin, resistin or adiponectin or on plasma lipid profile. Insulin sensitivity did not deteriorate during GH replacement despite the known ‘anti‐insulin’ effect of GH. Fasting glucose, insulin and insulin resistance as calculated using the homeostasis model assessment insulin resistance index (HOMA‐R) were unchanged by GH treatment.conclusion  These data demonstrate GH replacement in adult subjects with GHD is effective in changing body composition and restoring IGF‐I levels over a 12‐month period; however, in our study, these changes were not accompanied by changes in adipokine levels or beneficial effects on plasma lipids or insulin resistance.
Sex hormones in hereditary angioneurotic oedema
Authors: Visy B. , Füst G. , Varga L. , Szendei G. , Takács E. , Karádi I. , Fekete B. , Harmat G. , Farkas H. 
Published: December 2004

Summaryobjective  The fluctuations in sex hormone levels at the beginning of adolescence, in the perimenopausal period, during pregnancy or during the use of oral contraceptives can precipitate oedematous attacks in hereditary angioneurotic oedema (HANO). Attacks usually disappear after the onset of menopause. This study was undertaken to establish any relationship between the serum levels of sex hormones and the incidence of HANO attacks.patients and measurements  Serum levels of LH, FSH, progesterone, oestradiol, testosterone, PRL and SHBG were measured in 78 patients [mean age 30·3 years (range 4–70 years)] with HANO. A questionnaire was used to explore the medical history of adult patients to characterize the evolution and the characteristics of attacks.results  The number of attacks was significantly higher [odds ratio (OR) 6·36 (1·31–30·81); P = 0·022] in females with high progesterone levels (≥ 4 nmol/l), irrespective of age, menstrual cycle and danazol dose. The OR was even higher [13·4 (2·2–81·4); P = 0·005] when only subcutaneous attacks were considered. Multiple logistic regression analysis demonstrated a significantly lower attack frequency during 1‐year follow‐up in patients with a higher (40 nmol/l) SHBG level (OR 0·25 (0·07–0·90); P = 0·034). This difference existed independently of age and danazol dose.conclusion  In view of these results, the monitoring of progesterone and SHBG levels can prove useful in the prediction of attacks in hereditary angioneurotic oedema.
The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state
Authors: Broglio F. , Gianotti L. , Destefanis S. , Fassino S. , Abbate Daga G. , Mondelli V. , Lanfranco F. , Gottero C. , Gauna C. , Hofland L. , Van der Lely A. J. , Ghigo E. 
Published: December 2004

Summaryobjective  Ghrelin, a gastric‐derived natural ligand of the GH secretagogue (GHS)‐receptor (GHS‐R), strongly stimulates GH secretion but also possesses other neuroendocrine actions, stimulates food intake and modulates the endocrine pancreas and energy homeostasis. Ghrelin secretion is negatively modulated by food intake. Similarly, glucose and also insulin probably exert an inhibitory effect on ghrelin secretion. Fasting ghrelin levels are reduced in obesity, elevated in anorexia nervosa and restored by weight recovery. The chronic elevation of circulating ghrelin levels in anorexia suggested the hypothesis of an alteration of the sensitivity to the orexigenic action of ghrelin in this condition. The aim of this study was to define the endocrine actions of ghrelin in patients with anorexia nervosa.design  We enrolled nine women with anorexia nervosa of restricter type [AN; age (mean ± SEM) 24·2 ± 1·8 years; body mass index (BMI) 14·7 ± 0·4 kg/m2] and seven normal young women in their early follicular phase as control group (NW; age 30·6 ± 3·1 years; BMI 20·3 ± 0·5 kg/m2).measurements  In all the subjects we studied the GH, PRL, ACTH, cortisol, insulin and glucose responses to acute ghrelin administration (1·0 µg/kg as i.v. bolus). The GH response to GHRH (1·0 µg/kg as i.v. bolus) and basal ghrelin and IGF‐I levels were also evaluated in all the subjects.results  Basal morning ghrelin and GH levels in AN (643·6 ± 21·3 ng/l and 10·4 ± 0·5 µg/l, respectively) were higher (P < 0·05) than in NW (233·5 ± 14·2 ng/l and 0·7 ± 0·7 µg/l, respectively). However, IGF‐I levels in AN (145·3 ± 10·9 µg/l) were lower (P < 0·05) than in NW (325·4 ± 12·6 µg/l). The GH response to GHRH in AN was higher (P < 0·05) than that in NW, but in AN the GH response to ghrelin was lower (P < 0·05) than that in NW. In AN and NW ghrelin also induced similar increases (P < 0·05) in PRL, ACTH and cortisol levels. Ghrelin administration was followed by significant increase in glucose levels in NW (P < 0·05) but not in AN.conclusions  This study demonstrates that anorexia nervosa, a clinical condition of ghrelin hypersecretion, shows a specific reduction in the GH response to ghrelin, despite the hyper‐responsiveness to GHRH administration. The impaired GH response to ghrelin in anorexia nervosa agrees with previous evidence of blunted GH response to synthetic GH secretagogues and could reflect desensitization of the GHS receptor induced by the chronic elevation of ghrelin levels in this pathological state.
Circulating ghrelin levels in the newborn are positively associated with gestational age
Authors: Bellone S. , Rapa A. , Vivenza D. , Vercellotti A. , Petri A. , Radetti G. , Bellone J. , Broglio F. , Ghigo E. , Bona G. 
Published: December 2004

Summaryobjective  Ghrelin exerts potent GH‐releasing activity and stimulates food intake. Circulating ghrelin levels are increased in anorexia and cachexia, reduced in obesity and restored by weight recovery. Newborns are characterized by GH hypersecretion associated with low IGF‐I levels reflecting peripheral GH resistance.study design  The aim of our study was to measure cord ghrelin levels in 117 newborns appropriate for gestational age, born either at term or preterm.results  Ghrelin levels in cord blood (median; 25th−75th centile: 327·6; 206·0–413·0 pg/ml) were higher (P < 0·0001) than those in maternal blood at delivery (133·0; 89·0–173·7 pg/ml), without gender differences. A positive correlation between ghrelin levels in mothers and newborns (r = 0·26, P < 0·01) was observed. Ghrelin levels in newborns born at term (399·0; 229·0–438·0 pg/ml) were remarkably higher (P < 0·0001) than those in born preterm (208·0; 144·5–278·9 pg/ml). A clear positive association was present between ghrelin levels and gestational age. No association between ghrelin and GH, IGF‐I, insulin, glucose and leptin levels were found.conclusions  Cord ghrelin levels show clear gestational age‐related dependency. The lack of any direct relationship between ghrelin and anthropometric or biochemical parameters in adequate for gestational age newborns does not support the hypothesis that ghrelin has major role in foetal GH secretion and growth.
Neuroendocrine dysfunction in the acute phase of traumatic brain injury
Authors: Agha Amar , Rogers Bairbre , Mylotte Darren , Taleb Faisal , Tormey William , Phillips Jack , Thompson Christopher J. 
Published: December 2004

Summarybackground  Pituitary hormone abnormalities have been reported in up to 50% of survivors of traumatic brain injury (TBI) who were investigated several months or longer following the event. The frequency of pituitary dysfunction in the early post‐TBI period is unknown.aim  To evaluate the prevalence of anterior and posterior pituitary dysfunction in the early phase following TBI.subjects  Fifty consecutive patients admitted to the neurosurgical unit with severe or moderate TBI [initial Glasgow Coma Scale (GCS) score 3–13], and 31 matched healthy control volunteers were studied.methods  The glucagon stimulation test (GST) was performed at a median of 12 days (range 7–20) following TBI. Baseline thyroid function, PRL, IGF‐1, gonadotrophins, testosterone or oestradiol, plasma sodium, plasma and urine osmolalities or the standard observed water deprivation test were performed. The control subjects underwent the GST for GH and cortisol responses; other parameters were compared to locally derived reference ranges.results  Control data indicated that peak serum GH of > 5 ng/ml and cortisol > 450 nmol/l following glucagon stimulation should be taken as normal. Nine TBI patients (18%) had GH response < 5 ng/ml (12 mU/l). Eight patients (16%) had peak cortisol responses < 450 nmol/l. Compared to controls, basal cortisol values were significantly lower in patients with subnormal cortisol responses to glucagon and significantly higher in patients with normal cortisol responses (P < 0·05). GH and cortisol deficiencies were unrelated to patient age, BMI, initial GCS or IGF‐1 values (P > 0·05). Forty patients (80%) had gonadotrophin deficiency, with low sex steroid concentrations, which was unrelated to the presence of hyperprolactinaemia. In males there was a positive correlation between serum testosterone concentration and GCS (r = 0·32, P = 0·04). One patient had TSH deficiency. Hyperprolactinaemia was present in 26 patients (52%) and serum PRL levels correlated negatively with the GCS score (r =−0·36, P = 0·011). Thirteen patients (26%) had cranial diabetes insipidus (DI) and seven (14%) had syndrome of inappropriate ADH secretion.conclusion  Our data show that post‐traumatic neuroendocrine abnormalities occur early and with high frequency, which may have significant implications for recovery and rehabilitation of TBI patients.
Interest of Chromogranin A for diagnosis and follow‐up of endocrine tumours
Authors: Nehar D. , Lombard‐Bohas C. , Olivieri S. , Claustrat B. , Chayvialle J‐A. , Penes M‐C. , Sassolas G. , Borson‐Chazot F. 
Published: December 2004

Summaryobjective  To determine the interest of Chromogranin A (CgA) determination for diagnosis and follow‐up in patients with gastroenteropancreatic endocrine tumours (GEP‐ET) and multiple endocrine neoplasia type 1 (MEN‐1).patients and methods  CgA levels were measured with an immunoradiometric assay in 124 sporadic GEP‐ET, 34 MEN‐1 and 127 controls. Serial determinations were performed in 56 patients (212 visits). Changes in CgA levels over 25% were considered as significant.results  Using a cut‐off value of 130 µg/l, established from a receiver‐operating characteristic curve, the specificity of CgA was 98·4%, with a sensitivity of 62·9%, higher in secreting than in nonsecreting tumours (73%vs. 45%; P < 0·003) and related to the extent of metastatic spreading (P < 0·001). In nonsecreting tumours, the positive predictive value (PPV) of CgA for the presence of metastases was 100% but the negative predictive value (NPV) was only 50%. In MEN‐1, high CgA levels indicated a pancreatic tumour with a 100% specificity but the sensitivity was 59%. During the follow‐up, the concordance between CgA and tumour evolution was 80%, whatever the secretory status. In patients with carcinoid tumours, the concordance was higher for CgA than for serotonin (81%vs. 54%; P < 0·001).conclusion  Due to its high specificity, CgA determination may help to discriminate the endocrine character of a GEP tumour and to indicate a pancreatic tumour in MEN‐1. However, its low NPV in nonsecreting tumours limits its interest for diagnosis and staging. By contrast, serial evaluation of CgA seems of particular interest for the follow‐up of GEP‐ET tumours.