bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eating pattern and the effect of oral glucose on ghrelin and insulin secretion in patients with anorexia nervosa
Authors: Tanaka Muneki , Tatebe Yoshiki , Nakahara Toshihiro , Yasuhara Daisuke , Sagiyama Ken‐ichiro , Muranaga Tetsuro , Ueno Hiroaki , Nakazato Masamitsu , Nozoe Shin‐ichi , Naruo Tetsuro 
Published: October 2003

Summaryobjective  Ghrelin is thought to be involved in the regulation of eating behaviour and energy metabolism in acute and chronic feeding states. Circulating plasma ghrelin levels in healthy humans have been found to decrease significantly after oral glucose administration. Because it is suggested that eating behaviour may influence the secretion of ghrelin and insulin in anorexia nervosa (AN), we examined the effect of oral glucose on ghrelin and insulin secretion in subtypes of AN patients.design and patients  Twenty female AN patients and 10 age‐matched female controls were subjects. The patients were subdivided into two subtypes based on eating behaviour as follows: 11 restricting type (AN‐R), nine binge‐eating and purging type (AN‐BP). Subjects underwent an oral glucose tolerance test at 08·00 h. Blood was collected 0, 30, 60, 120 and 180 min after the glucose load.results  Both AN‐R and AN‐BP had a significant increased basal ghrelin level (P < 0·01) and a significantly decreased basal insulin level (P < 0·05) as compared to controls. The time of the nadir of mean ghrelin in AN‐BP (120 min, 58·1% of basal level, 204·9 ± 34·3 pmol/l, mean ± SEM) was delayed compared to controls (60 min, 60·2%, 74·3 ± 7·9 pmol/l), and in the AN‐R group it kept decreasing for 180 min (80·0%, 182·4 ± 31·5 pmol/l). The peaks insulin levels in AN‐BP (120 min, 319·3 ± 88·8 pmol/l) and AN‐R (180 min, 418·9 ± 68·4 pmol/l) were also delayed as compared to controls (60 min, 509·2 ± 88·8 pmol/l). The glucose level at 180 min in AN‐R was significantly (P < 0·05) higher than in controls.conclusions  These findings suggest that differences in eating behaviour in AN may induce alterations in both ghrelin and insulin metabolism in the acute feeding state. Furthermore, metabolic changes in the restrictive eating pattern may be related to the pathophysiology of small quantitative meal intake in AN‐R patients.
The TSH response to domperidone reflects the biological activity of prolactin in macroprolactinaemia and hyperprolactinaemia
Authors: Pinto L. P. , Hanna F. W. F. , Evans L. M. , Davies J. S. , John R. , Scanlon M. F. 
Published: October 2003

Summaryobjective  To test the hypothesis that patients with hyperprolactinaemia due to biologically inactive macroprolactin will not show the characteristically increased dopaminergic inhibition of TSH release seen in patients with microprolactinomas secreting biologically active monomeric PRL.design  Comparison of the TSH and PRL responses to dopamine antagonism with domperidone (10 mg i.v.) in patients with hyperprolactinaemia due to macroprolactinaemia or microprolactinomas.patients  Twenty‐two patients referred for the investigation of their hyperprolactinaemia were studied: 11 patients with macroprolactinaemia and 11 patients with hyperprolactinaemia due to microprolactinoma.measurements  TSH and PRL levels were measured at baseline and 30 min following domperidone in both groups.results  Patients with macroprolactinaemia showed normal TSH and PRL responses to dopamine antagonism whereas patients with microprolactinomas showed exaggerated TSH responses and reduced PRL responses. Although there was considerable overlap between the PRL responses in the two groups, there was very clear separation between the PRL/TSH response ratios (normal > 1·0) of 4·0 ± 1·8 for the macroprolactinaemia group and 0·4 ± 0·2 for the microprolactinoma group (P < 0·0001).conclusions  These data support the hypothesis that elevated circulating levels of macroprolactin, as opposed to biologically active monomeric PRL, do not exert increased positive feedback on the hypothalamic dopaminergic inhibition of TSH release.
Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index
Authors: Van Rossum Elisabeth F. C. , Koper Jan W. , Van Den Beld Annewieke W. , Uitterlinden André G. , Arp Pascal , Ester Wietske , Janssen Joop A. M. J. L. , Brinkmann Albert O. , De Jong Frank H. , Grobbee Diederick E. , Pols Huibert A. P. , J. Lamberts Steven W. 
Published: October 2003

Summaryobjective  Sensitivity to glucocorticoids differs between individuals, partially due to genetic variation in the glucocorticoid receptor (GR) gene. We studied the sequence alteration of a previously described intronic BclI polymorphism of the GR gene, and investigated whether there was an association with sensitivity to glucocorticoids and anthropometric parameters in a group of healthy elderly individuals.design and measurements  In study group 1, two overnight dexamethasone suppression tests (DSTs) were performed: with 1 mg dexamethasone, and 2·5 years later with 0·25 mg dexamethasone. Anthropometric parameters were measured in a larger population (study group 2), as well as in a third study group, in which we also measured body composition by dual‐energy X‐ray absorbtiometry (DEXA) scans.subjects  Groups 1 and 2, respectively, 191 and 1963 male and female participants of the Rotterdam study, a population‐based study in Dutch elderly. Study group 3: 370 elderly males (mean age 77·8 ± 0·2 years) from Zoetermeer, the Netherlands.results  We identified the BclI restriction site polymorphism as a C/G substitution in intron 2, 646 nucleotides downstream from exon 2. After both 1 mg and 0·25 mg DST, heterozygous (CG) and homozygous G‐allele carriers (GG) had lower cortisol levels than CC‐carriers (P = 0·01 and P = 0·02, respectively). In study group 2, we found a lower body mass index (BMI; P = 0·006) and waist–hip ratio (WHR; P = 0·02) in G‐allele carriers. In study group 3, again we found a lower BMI (P = 0·05) in G‐allele carriers. No differences were found in fat mass. However, lean mass tended to be lower in G‐allele carriers (P = 0·07).conclusions  We characterized a BclI‐RFLP (restriction fragment length polymorphism) of the GR gene as a C/G polymorphism in intron 2 of which the G‐allele was associated with hypersensitivity to glucocorticoids. This resulted in a lower BMI in older individuals in general, while our study in elderly males suggests that the lower BMI is probably due to a greater loss of lean mass during the ageing process.
Prevalence of adrenal antibodies in Addison's disease among north Indian Caucasians
Authors: Nigam R. , Bhatia E. , Miao D. , Yu L. , Brozzetti A. , Eisenbarth G. S. , Falorni A. 
Published: October 2003

Summaryobjective  The prevalence of antibodies in different organ‐specific autoimmune diseases can vary depending on the racial group studied. Data on the prevalence of antibodies against steroidogenic enzymes in Addison's disease is available only for white Caucasians. We have evaluated the frequency of antibodies against adrenal cytoplasm, 21‐hydroxylase, 17‐α‐hydroxylase and side‐chain cleavage enzyme in a cohort of Indian patients with Addison's disease of idiopathic and granulomatous aetiology.design  Study of all patients with Addison's disease on whom serum samples were available (84% of total), presenting to the Endocrinology Department in a teaching hospital in India, between 1990 and 1999.patients  Thirty‐eight patients with Addison's disease (19 idiopathic, 19 granulomatous).methods  A radiobinding assay using in vitro transcribed and translated recombinant human 35S‐labelled 21‐hydroxylase, 17‐α‐hydroxylase and side‐chain cleavage enzymes was utilized to detect the respective antibodies. Adrenal cytoplasmic antibodies were measured by indirect immunofluorescence on cryostatic sections of human adrenal cortex.results  Of the 19 patients with idiopathic Addison's disease, adrenal cytoplasmic antibodies were present in five (26%) patients, while 21‐hydroxylase antibodies were present in four (21%) subjects. The frequency of 21‐hydroxylase antibodies was similar among patients with isolated idiopathic Addison's disease (3/13, 23%), and those associated with other organ‐specific autoimmune diseases (1/6, 17%). 17‐α‐hydroxylase and side‐chain cleavage antibodies were present in four (21%) and three (16%) patients, respectively. Overall, at least one of the three antibodies was present in eight (42%) subjects. All four female patients with premature ovarian failure had antibodies against 17‐α‐hydroxylase and/or side‐chain cleavage enzyme. Two (11%) patients with granulomatous Addison's disease had adrenal antibodies. Of these, one patient with enlarged and calcified adrenal gland secondary to tuberculosis had a high titre of antibodies against all three steroidogenic enzymes.conclusions  Antibodies to 21‐hydroxylase enzyme are less frequent in idiopathic Addison's disease in north Indians, when compared with other Caucasians. In contrast, the prevalence of 17‐α‐hydroxylase and side‐chain cleavage enzyme antibodies is similar to those reported. High titre antibodies against steroidogenic enzymes may occasionally be present in patients with clinical evidence of tuberculous Addison's disease.
Insulin gene VNTR genotype is associated with insulin sensitivity and secretion in infancy
Authors: Bazaes R. A. , Petry C. J. , Ong K. K. , Ávila A. , Dunger D. B. , Mericq M. V. 
Published: October 2003

Summaryaims  We have previously demonstrated that insulin sensitivity and secretion at age 1 year was in part related to variation in weight and height gain during infancy. In order to determine whether genetic variation at the insulin gene could also influence these associations, we have studied the relationship between insulin gene variable number of tandem repeat (INS VNTR) genotypes, insulin secretion and early postnatal growth.methods  We assessed fasting and dynamic insulin secretion in 99 healthy infants at age 1 year, using a short intravenous glucose tolerance test (sIVGTT). Infants were genotyped at the –23 HphI locus, as a surrogate marker for INS VNTR allele classes I and III. Anthropometric data were recorded at birth and at 1 year. Data are shown as median (interquartile range).results  Fasting insulin levels were higher in III/III infants (n = 9) than in I/I infants [n = 55; 27·4 (17·6–75·6) pmol/l vs. 18·1 (10·3–25·2) pmol/l; P < 0·05]. Insulin secretion during the sIVGTT, as estimated by the serum insulin area under the curve, was also higher in III/III infants [2417 (891–4041) pmol min/l vs. 1208 (592–2284) pmol min/l; P < 0·05]. Fasting and postload plasma glucose levels were similar in both groups. Analysis of covariance showed that genotype differences in fasting insulin sensitivity and insulin secretion were independent of size at birth, postnatal growth velocity and current body mass index.conclusions  Significant associations between INS VNTR genotype and both insulin sensitivity and secretion were apparent in infancy; these might interact with childhood appetite and nutrition to impact the development of childhood obesity and insulin resistance.
Impaired GH secretion to provocative stimuli in two families with hypocalciuric hypercalcaemia
Authors: Cecconi Elisabetta , Bogazzi Fausto , Cetani Filomena , Grasso Lucia , Marcocci Claudio , Genovesi Maura , Procopio Massimo , Gasperi Maurizio , Pinchera Aldo , Ghigo Ezio , Martino Enio 
Published: October 2003

Summaryobjective  To determine whether hypercalcemia per se might be responsible for an impairment in GH secretion.design  Prospective study.patients  Six subjects of two unrelated families with familial hypocalciuric hypercalcaemia (FHH), an autosomal dominant disorder due to inactivating mutations in the calcium receptor gene, leading to an increase in serum calcium levels and inappropriately normal serum PTH concentrations. Forty normal subjects, matched for sex and age served as controls.measurements  Serum GH concentrations were measured after GHRH‐Arginine (GHRH‐Arg) stimulation test; serum IGF‐I, ACTH, cortisol, FT4, FT3, TSH, PRL, LH, FSH levels were measured under basal conditions.results  All subjects (two male, four female, age range 24–74 years) had increased serum ionized calcium levels (range 1·36–1·56 mmol/l) and five of six patients had normal PTH levels (range for all patients was 14–68 ng/l). Basal serum GH concentrations ranged from 0·1 to 7·0 µg/l. Mean serum GH secretory peak after GHRH‐Arg stimulation test was reduced in five subjects (mean 9·3 ± 3·6 µg/l, P < 0·006 vs. Controls, mean 67·0 ± 44·0 µg/l, cut‐off, 16·0 µg/l) and normal in one subject (38·7 µg/l). However, serum IGF‐I levels were reduced only in two patients (29 and 57 µg/l) and normal in four subjects (range 127–208 µg/l). The basal secretion of the other anterior pituitary hormones was within their normal ranges.conclusions  The results of the present study support the concept that elevated serum calcium levels impair GH secretion. However, the clinical relevance of GH deficiency in FHH remains to be elucidated.
Decrease in carotid intima‐media thickness in hypothyroid patients after normalization of thyroid function
Authors: Nagasaki Toshiki , Inaba Masaaki , Henmi Yasuko , Kumeda Yasuro , Ueda Misako , Tahara Hideki , Sugiguchi Shigeru , Fujiwara Shigehiko , Emoto Masanori , Ishimura Eiji , Onoda Naoyoshi , Ishikawa Tetsuro , Nishizawa Yoshiki 
Published: October 2003

Summaryobjective  This case–control study was carried out to assess whether levothyroxine (L‐T4) replacement might cause regression of the enhanced atherosclerosis seen in hypothyroid patients.patients and methods  Intima‐media thickness (IMT) in the common carotid artery (CCA) was measured from digitalized still images taken during scanning by high‐resolution ultrasonography as an indicator of early atherosclerosis. Thirty‐five hypothyroid patients were examined for their CCA IMT before and 1 year after normalization of thyroid function by L‐T4 replacement. As control, 35 healthy subjects were enrolled from among the participants in a local health‐check programme conducted at the Osaka City University Hospital.results  Basal CCA IMT was significantly higher in hypothyroid patients [0·635 ± 0·018 (mean ± SE) mm] than in control subjects (0·559 ± 0·021 mm, P < 0·005). After 1 year of euthyroidism, 34 out of 35 patients showed a significant decrease of CCA IMT, to 0·552 ± 0·015 mm (P < 0·0001), a level comparable to normal controls. CCA IMT change was closely associated with basal levels of total cholesterol (r = −0·472, P= 0·0031), low‐density lipoprotein (LDL) cholesterol (r = −0·441, P= 0·0076) and the total/HDL cholesterol ratio (r =−0·435, P= 0·0057), but not with any of the other variables measured except for age (r = −0·353, P= 0·0296).conclusions  This study demonstrated that L‐T4 treatment might have the potential to reverse the progression of atherosclerosis in hypothyroid patients. Furthermore, it suggests that increased levels of LDL cholesterol and the total/HDL cholesterol ratio have an important role in the increased common carotid intima‐media thickness in hypothyroid patients.
The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement
Authors: Swords F. M. , Carroll P. V. , Kisalu J. , Wood P. J. , Taylor N. F. , Monson J. P. 
Published: October 2003

Summaryobjective  11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) converts inactive cortisone to active cortisol. 11βHSD1 activity is increased in GH deficiency and inhibited by GH and IGF‐I in acromegaly. However it is not known whether these changes in cortisol metabolism exert significant effects during hydrocortisone therapy, and the effect has not been studied in patients taking cortisone acetate. We have studied the effect of GH induced 11βHSD1 inhibition in hypopituitary adults with severe GH deficiency to determine whether this inhibition has a different magnitude of effect when patients are taking different forms of glucocorticoid replacement therapy.design, patients and measurements  We have taken the ratio of 11‐hydroxy/11‐oxo cortisol metabolites (Fm/Em), an established measure of net 11βHSD activity to reflect the likely balance of cortisol to cortisone exposure in tissues expressing 11βHSD1, principally the liver and adipose tissue. We recruited 10 hypopituitary adults all on established glucocorticoid replacement therapy, but who were not receiving GH. Patients were treated with their standard hydrocortisone therapy for one week and an equivalent dose of cortisone acetate in its place for one week in random order. Serial serum cortisol assessments and urine steroid profiles were performed on each treatment. All patients were then established on GH therapy for at least three months before the two‐week cycle was repeated. Fm/Em was also measured in a control population (20F, 20M).results  Prior to GH, the ratio Fm/Em was greater with hydrocortisone compared with cortisone acetate replacement (1·17 ± 0·28 and 0·52 ± 0·09 respectively, P < 0·001) or with normal subjects (normal males: 0·81 ± 0·24, females 0·66 ± 0·14). Following GH replacement Fm/Em fell in patients on hydrocortisone and cortisone acetate (Pre‐GH: 0·84 ± 0·40, Post‐GH: 0·70 ± 0·34, P < 0·05) confirming the inhibition of 11βHSD1 by GH/IGF‐I. Conversely, the ratio of urinary free cortisol/cortisone did not change indicating unchanged 11βHSD2 activity. Mean circulating cortisol also fell in all subjects after GH. This effect was greater during cortisone acetate treatment (−18·7%, P < 0·0001), than during hydrocortisone replacement (−10·9%, P < 0·05).conclusions  Our data suggest that tissue exposure to glucocorticoid is supra‐physiological in hypopituitary patients with untreated GH deficiency taking hydrocortisone replacement therapy. This situation is ameliorated by GH replacement therapy. However, local and circulating cortisol concentrations are more vulnerable to the inhibitory effect of GH on 11βHSD1 in patients taking cortisone acetate, such that serum cortisol assessments should be made in patients taking cortisone acetate after GH therapy to ensure that glucocorticoid replacement remains adequate.
Serum concentrations of adipocytokines in patients with hyperthyroidism and hypothyroidism before and after control of thyroid function
Authors: Iglesias Pedro , Alvarez Fidalgo Pilar , Codoceo Rosa , Díez Juan J. 
Published: October 2003

Summaryobjective  Adipose tissue is a hormonally active system that produces and releases different bioactive substances. Leptin, adiponectin and resistin are some of the recently discovered adipocytokines that participate in the regulation of intermediate metabolism. The aim of this study was to evaluate the circulating levels of leptin, adiponectin and resistin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy.patients and measurements  We studied 20 patients with hyperthyroidism (16 women and 4 men; mean age 47·2 ± 3·9 years) and 20 patients with hypothyroidism (17 women and 3 men; 51·5 ± 4·1 years). A group of 20 euthyroid subjects served as control group. Patients were evaluated at the time of diagnosis and again after normalization of thyroid function with appropriate therapy. Serum concentrations of free T4 (FT4), total T3, TSH, insulin, leptin, adiponectin and resistin were measured in all subjects.results  Hyperthyroid patients showed significantly decreased leptin levels in comparison with controls (11·0 ± 1·1 vs. 30·4 ± 5·0 µg/l, P < 0·001). No significant differences in adiponectin levels between hyperthyroid and control groups were found (27·8 ± 4·0 vs. 46·0 ± 12·0 mg/l, NS). Patients with hyperthyroidism exhibited reduced resistin levels in comparison with euthyroid subjects (6·4 ± 0·8 vs. 8·4 ± 0·7 µg/l, P < 0·05). Normalization of circulating thyroid hormone was accompanied by a nonsignificant increase in leptin levels (12·9 ± 1·7 µg/l, P < 0·01 vs. control) and no significant modification both in adiponectin (32·0 ± 7·1 mg/l, NS) and resistin (5·4 ± 0·7 µg/l, NS) levels. Adjustment of adipocytokine concentrations for body mass index (BMI) showed that treatment of hyperthyroidism induced a significant reduction in adjusted resistin concentrations (0·21 ± 0·03 vs. 0·28 ± 0·03 µg/l/BMI units, P < 0·05), with no changes in adjusted leptin and adiponectin. Hypothyroid patients showed significantly lower leptin levels compared with the controls (16·0 ± 3·5 vs. 30·4 ± 5·0 µg/l, P < 0·05). Adiponectin levels in patients with hypothyroidism (71·8 ± 16·0 mg/l) were similar to those in the control group and were not modified with therapy. Resistin levels were significantly reduced among hypothyroid patients (5·8 ± 1·0 µg/l, P < 0·05), and were not increased after levothyroxine therapy. A significant rise in BMI‐corrected leptin levels was observed after replacement therapy, with no changes in adiponectin‐ and resistin‐corrected values.conclusions  The results suggest that (1) low serum leptin levels are present in both hyperthyroid and hypothyroid patients but are only increased after therapy in the latter; (2) resistin might be implicated in the insulin resistance state that accompanies thyrotoxicosis; and (3) inadequate secretion of adiponectin seems to have no role in metabolic changes associated with thyroid dysfunction.
Ghrelin mRNA and GH secretagogue receptor mRNA in human GH‐producing pituitary adenomas is affected by mutations in the α subunit of G protein
Authors: Kim Kyongsong , Sanno Naoko , Arai Keiko , Takano Koji , Yasufuku‐Takano Junko , Teramoto Akira , Shibasaki Tamotsu 
Published: October 2003

Summaryobjective  Ghrelin and its receptor, growth hormone secretagogue (GHS) receptor (GHSR), are expressed in the normal pituitary gland and various types of pituitary adenoma. Somatic mutations in the subunit of Gs α protein (gsp), which led to a constitutive activation of adenylyl cyclase, are reported in GH‐producing pituitary adenomas. We analysed the relationship between ghrelin mRNA and GHSR mRNA expression levels in gsp mutation‐positive and ‐negative GH‐producing pituitary adenomas.patients  Pituitary adenoma tissue was obtained at surgery from 20 patients with acromegaly.methods  The expression levels of human ghrelin mRNA and GHSR mRNA were quantified using a competitive RT–PCR method. To detect the gsp mutations, amplified Gs α subunit cDNA fragments were sequenced directly using RT–PCR method.results  There was no significant difference in the expression of ghrelin mRNA between mutation‐positive and ‐negative adenomas. The expression of GHSR mRNA was significantly lower in gsp mutation‐positive than ‐negative adenomas. There was a significant negative correlation between the levels of ghrelin mRNA and GHSR mRNA expression in mutation‐negative adenomas; no such correlation was found in mutation‐positive adenomas.conclusion  These results suggest that GHSR mRNA expression is downregulated by ghrelin in gsp mutation‐negative GH‐producing pituitary adenomas, and that changes in intracellular signalling pathways in gsp mutation‐positive GH‐producing pituitary adenomas affect the expression of G protein‐coupled receptors such as GHSR. The absence of negative correlation between ghrelin and GHSR expression might be induced by lowered GHSR expression in gsp mutation‐positive GH‐producing adenomas.