bluuebunny/crossref_metadata_2025_split huggingface dataset:
The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF‐I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population
Authors: Janssen J. A. M. J. L. , Huizenga N. A. T. M. , Stolk R. P. , Grobbee D. E. , Pols H. A. P. , De Jong F. H. , Attanasio A. M. F. , Blum W. F. , Lamberts S. W. J. 
Published: March 2003

OBJECTIVETo investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF‐I/IGFBP system and leptin levels in healthy elderly humans.METHODSIn 209 healthy elderly individuals (95 men, 114 women, aged 55–80 years) measurements were made in the fasting state (0800 h) and after an overnight dexamethasone suppression test (1 mg p.o. at 2300 h.RESULTSMean leptin levels increased from 6.2 ± 0.4 (SE) μg/l to 7.3 ± 0.5 (SE) μg/l in men and from 18.9 ± 1.4 (SE) μg/l to 23.9 ± 1.8 (SE) μg/l in women after 1 mg dexamethasone overnight (‘post treatment’) (P < 0.001 for both sexes). There was a significant relationship between post‐treatment leptin and dexamethasone levels (men: P = 0.002; women: P < 0.001). The increase in leptin levels after dexamethasone administration was only partially related to the increase in plasma insulin concentrations. Cortisol levels were not related to leptin. In multivariate analyses the relationship between post‐treatment leptin and dexamethasone levels remained after adjustment for post‐treatment insulin levels, BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women: P = 0.001). Plasma (free and total) IGF‐I and IGFBP‐3 levels were not related to leptin levels in men or women. IGFBP‐1 levels were inversely related to leptin levels (P = 0.02), but this relationship was lost after adjustment for insulin, and/or BMI. In multivariate analyses the relationship between leptin and DHEAS was inverse in women (P = 0.04) (after adjustment for BMI, WHR, insulin and glucose), while there was no relationship between leptin and DHEAS in men.CONCLUSIONSAdministration of dexamethasone acutely increased leptin levels within 9 h in this elderly population. This increase was only partly related to changes in circulating insulin concentrations, but was independent of BMI and waist:hip ratio. No relation existed between leptin and (free or total) IGF‐I and IGFBP‐3 in men or women. Dehydroepiandrosterone was inversely related to leptin in women. These findings suggest a contributory regulatory role for corticosteroids in modulating circulating leptin concentrations in elderly healthy individuals of both sexes, which is at least in part independent of insulin, BMI and waist:hip ratio. Dehydroepiandrosterone might play a role in the gender‐specific differences in serum leptin levels.
Reduced serum dehydroepiandrosterone levels in diabetic patients with hyperinsulinaemia
Authors: Yamaguchi Yumiko , Tanaka Shun‐ichi , Yamakawa Tadashi , Kimura Mari , Ukawa Kunio , Yamada Yoshihiko , Ishihara Manabu , Sekihara Hisahiko 
Published: March 2003

OBJECTIVETo elucidate the interaction between insulin and dehydroepi‐androsterone (DHEA) concentrations, we evaluated serum DHEA and DHEA‐sulphate (DHEA‐S) levels in diabetic patients with hyperinsulinaemia.PATIENTS AND DESIGNTwenty‐four subjects with non‐insulin dependent diabetes mellitus, 12 hyperinsulinaemic subjects (fasting serum insulin concentrations 10 mU/ml (71.8 pmol/l)) and 12 non‐hyperinsulinaemic subjects, and 10 normal control subjects were studied. Serum DHEA, DHEA‐S, cortisol and ACTH levels were investigated in these subjects. Moreover, their serum DHEA levels were compared during hyperinsulinaemic–euglycaemic clamp and after ACTH stimulation.MEASUREMENTSSerum insulin, cortisol, ACTH, DHEA and DHEA‐S concentrations were evaluated by RIA. Serum glucose was determined by the glucose oxidase method.RESULTSDiabetic patients with hyperinsulinaemia showed significantly lower levels of serum DHEA and DHEA‐S than controls. After ACTH stimulation, these patients also showed significantly lower DHEA levels. During the hyperinsulinaemic–euglycaemic clamp, serum DHEA concentrations of diabetic patients with hyperinsulinaemia remained low and did not decline further, although those of control subjects and non‐hyperinsulinaemic diabetic patients showed a significant decline of serum DHEA levels. Even after ACTH stimulation during the clamp, serum DHEA in hyperinsulinaemic patients was still significantly lower than in controls.CONCLUSIONSIn diabetic patients with hyperinsulinaemia, baseline DHEA levels are chronically and maximally suppressed compared to control subjects and non‐hyperinsulinaemic diabetic patients, and thus not decreased further by exogenous insulin infusion during hyperinsulinaemic–euglycaemic clamp.
A study of patients with Nelson's syndrome
Authors: Pereira Maria A. Albergaria , Halpern Alfredo , Salgado Luiz Roberto , Mendonça Berenice B. , Nery Marcia , Liberman Bernardo , Streeten David H. P. , Wajchenberg Bernardo L. 
Published: March 2003

OBJECTIVEThe prevalence of Nelson's syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelson's syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushing's disease after bilateral adrenalectomy. We have compared patients with Cushing's disease who developed Nelson's syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelson's syndrome.PATIENTS AND METHODSWe have reviewed the records of 30 patients with Cushing's disease after adrenalectomy, and divided them into two groups; I: 14 who developed Nelson's syndrome and II, 16 who did not. The two groups of patients were compared in their clinical, laboratory and imaging data as well as in the therapeutic procedures that preceeded the adrenalectomy.RESULTSThe comparison between the two groups of patients demonstrated a highly significant difference in relation to the development of cutaneous hyperpigmentation (100% in group I and 19% in group II) and neuro‐ophthalmological symptoms (21% in group I and 0% in group II) after adrenalectomy. There were no significant differences in laboratory data before adrenalectomy. After adrenalectomy, plasma ACTH levels increased significantly in the patients of both groups, but to much higher levels in those who developed Nelson's syndrome. Plasma ACTH concentrations above 154 pmol/l occurred only in the subjects with Nelson's syndrome. Before adrenalectomy, a pituitary tumour was more frequent in the patients who developed Nelson's syndrome (55% vs. 33% at transsphenoidal pituitary exploration). Pituitary surgery and irradiation were undertaken before adrenalectomy in approximately equal numbers of patients in each group.DISCUSSIONThe prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.
A cytotoxic T lymphocyte antigen‐4 (CTLA‐4) gene polymorphism is associated with autoimmune Addison's disease in English patients
Authors: Kemp  , Ajjan  , Husebye  , Peterson  , Uibo  , Imrie  , Pearce  , Watson  , Weetman  
Published: March 2003

OBJECTIVERecent studies have demonstrated an association between a microsatellite polymorphism of the CTLA‐4 gene, specifically a 106 base pair allele, and both Graves' disease and autoimmune hypothyroidism. The aim of the present study was to determine whether the same polymorphism of the CTLA‐4 gene was associated with autoimmune Addison's disease.DESIGN AND PATIENTSWe analysed a microsatellite polymorphism (variant lengths of a dinucleotide (AT)n repeat) within exon 3 of the CTLA‐4 gene in the following groups: 21 English patients with non‐associated Addison's disease, 18 with autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy control subjects; 26 Norwegian patients with non‐associated Addison's disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17 with APS2 and 100 controls; 3 Finnish patients with non‐associated Addison's disease, 5 with APS2 and 71 controls; 10 Estonian patients with non‐associated Addison's disease, 2 with APS2 and 45 controls.MEASUREMENTSThe CTLA‐4 microsatellite gene polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and resolution of the products on sequencing gels.RESULTSThe frequency of the 106 base pair allele was significantly increased in the groups of English patients with either non‐associated Addison's disease or APS2 (P = 0.02 and 0.04, respectively), when compared to healthy controls with no clinical evidence or family history of either Addison's disease or any other autoimmune disorder. For Norwegian patients with either non‐associated Addison's disease, APS1 or APS2, there was no association (P = 0.69, 0.62 and 0.97, respectively). This was also the case for Finnish patients with either non‐associated Addison's disease or APS2 (P = 0.23 and 0.28, respectively) and for Estonian patients with either non‐associated Addison's disease or APS2 (P = 0.34 and 0.29, respectively).CONCLUSIONSThese results indicate that differences exist in the frequency of the 106 base pair allele in different population groups and in only the English population was the 106 base pair allele associated with Addison's disease.
HDL‐cholesterol reductions associated with adult growth hormone replacement
Authors: Leese  , Wallymahmed  , VanHeyningen  , Tames  , Wieringa  , MacFarlane  
Published: March 2003

OBJECTIVETo study the effects of human growth hormone (hGH) replacement on serum lipids and lipoprotein (a) (Lp(a)) concentrations.DESIGNA randomized double blind placebo controlled trial for 6 months followed by an open trial where all patients were treated with hGH for a further 6 months. Treatment was with recombinant hGH given in a dose of 0.125U/kg/wk increasing to 0.25U/Kg/wk.PATIENTSThirty two patients with growth hormone deficiency were recruited, but two withdrew because of side effects. Of the thirty patients (age 35.1 ± 11.8 year; mean ±SD) completing the study 13 of were assigned to the placebo group for six months and 17 to active treatment from the start.MEASUREMENTSFasting serum samples were analysed for total cholesterol, High density lipoprotein (HDL)‐cholesterol, HDL‐subfractions, triglycerides, lipoprotein (a) (Lp(a)) and IGF‐1. LDL‐cholesterol was calculated using the Friedewald formula.RESULTSCompared to placebo, 6 months treatment with hGH therapy resulted in increased IGF‐1 (37.6 ± 4.1 vs. 14.0 ± 2.2 nmol/l, P < 0.01), but there was no significant difference in any of the lipid parameters measured between placebo and active treatment groups at 6 months. hGH was associated with a decrease in HDL‐cholesterol concentration from baseline to 6 months (0.97 ± 0.08 to 0.76 ± 0.10 mmol/l P < 0.01), especially within the HDL2 subfraction. This reduction was maintained at 12 months. There was no change in Lp(a) concentrations from 0 to 6 months (placebo −26 (−340 to 82), median and range, active −4 (−586 to 212) mg/l). There was no change in total cholesterol, LDL‐cholesterol, triglycerides or proportion of HDL subfractions.CONCLUSIONSTreatment with hGH can reduce serum HDL‐cholesterol concentrations. Further investigation of this is required.
No overrepresentation of congenital adrenal hyperplasia in patients with adrenocortical tumours
Authors: Kjellman Magnus , Holst Mikael , Bäckdahl Martin , Larsson Catharina , Farnebo Lars‐Ove , Wedell Anna 
Published: March 2003

OBJECTIVEThe development and progression of sporadic adrenocortical tumours are poorly understood. In autopsy studies adrenocortical tumours are found in between 2 and 9% of the general population. In congenital adrenal hyperplasia (CAH), decreased production of cortisol leads to increased secretion of ACTH from the pituitary, resulting in hyperplasia of the adrenals. More than 95% of all cases of CAH are due to steroid 21‐hydroxylase deficiency, resulting from mutations in the CYP21 gene. In subjects homozygous and heterozygous for CYP21 mutations, adrenocortical tumours have been found in a high frequency compared to the general population, suggesting that chronic ACTH stimulation may play a role in the development of this tumour form. In order to test whether mild undiagnosed CAH is a common predisposing factor, we screened 27 patients with sporadic adrenocortical tumours for CYP21 mutations.DESIGNA retrospective study.PATIENTSWe screened 27 patients with sporadic adrenocortical tumours, representing both benign and malignant as well as hormonally active and silent lesions.MEASUREMENTSMutation analyses of the CYP21 gene was performed by allele‐specific PCR on high molecular weight DNA. The method used detects the nine CYP21 mutations that are responsible for 95% of all disease‐causing alleles in CAH.RESULTSNo mutations were detected in any of the 23 DNA samples that were prepared from leucocytes. In 4 cases where no leucocyte DNA was available, tumour tissue was analysed. In one of these tumours, two CYP21 mutations, V281 L and L307insT, were found in heterozygous form.CONCLUSIONOur data indicate that mild undiagnosed congenital adrenal hyperplasia is not a common underlying factor predisposing to adrenocortical tumours, at least not in the Swedish population.
Inhibin forms in serum from postmenopausal women with ovarian cancers
Authors: Robertson David M. , Cahir Nicholas , Burger Henry G. , Mamers Pamela , Groome Nigel 
Published: March 2003

BACKGROUND AND OBJECTIVEPrevious studies have shown that serum inhibin as measured by α subunit‐directed radioimmunoassay (RIA) and inhibin A ELISA was elevated in postmenopausal women with mucinous and granulosa cell cancers, with the RIA showing a more frequent elevation than the inhibin A ELISA. It was thus hypothesised that these cancers may also produce inhibin B or the free α subunit. The aim of the study was to identify the forms of inhibin found in a range of ovarian cancers using a range of inhibin assays with varying specificities.DESIGNSerum samples obtained from women with ovarian cancer were assayed by inhibin B ELISA and Pro‐αC subunit ELISA and compared with inhibin RIA and inhibin A ELISA.PATIENTSBlood samples were obtained from 34 postmenopausal women (>55 years) with no history of endocrine disease and from women with ovarian serous cystadenocarcinomas (n = 66), mucinous cystadenocarcinomas (n = 20), granulosa cell tumours (n = 9 − 11), miscellaneous ovarian cancers (n = 46) and non ovarian cancers (n = 23).MEASUREMENTSInhibin B and inhibin Pro‐αC subunit levels were determined by ELISA and compared to values obtained by RIA and inhibin A ELISA. Cancers were discriminated from controls based on values obtained 2SD above the geometric mean of the control values.RESULTSGranulosa cell tumours were detected by RIA and inhibin B ELISA (100%), Pro‐αC ELISA (90%) and inhibin A ELISA (77%). Mucinous tumours were detected by RIA (70%), inhibin B ELISA (60%), Pro‐αC ELISA (55%) and inhibin A (20%). Serous tumours were detected by RIA (35%) and the other assays (<15%). Miscellaneous tumours were detected by RIA (41%) and other assays <30%.CONCLUSIONSOvarian neoplasms may produce a variety of peptides related to the inhibins, including dimeric inhibin A and B. Inhibin B is detected in more ovarian cancers than inhibin A but does not discriminate as well as the α subunit directed assays. The higher discrimination index obtained with the RIA compared to the Pro‐αC ELISA suggests that assays detecting all inhibin forms containing the α subunit and not just those detecting the Pro‐αC subunit will provide the most useful detection method.
High prevalence of osteoporosis in cardiac transplant recipients and discordance between biochemical turnover markers and bone histomorphometry
Authors: Glendenning Paul , Neil Kent G. , Adler Brendan D. , Matz Leonard , Watson Ian , O'Driscoll Gerry J. , Hurley David M. 
Published: March 2003

OBJECTIVEAll patients attending the cardiac trans‐plantation clinic at the Royal Perth Hospital were investigated to determine the prevalence of osteoporosis and to assess changes in bone metabolism and histomorphometry in a cohort of cardiac transplant recipients.DESIGNRetrospective cross‐sectional study.PATIENTSThirty‐two patients (27 male; 5 female) who had received a cardiac transplant during the past 10 years and who were receiving immunosuppressive therapy with cyclosporin, azathioprine and prednisolone were studied.MEASUREMENTSAll patients had bone densitometry by DEXA of the lumbar spine and femoral neck and X‐rays of the thoracolumbar spine. Fasting serum ionized calcium, intact PTH, creatinine, 25 hydroxy‐vitamin D, alkaline phosphatase, osteocalcin, testosterone and free thyroxine and urine calcium, creatinine, hydroxyproline and deoxypyridinoline were measured. Six osteoporotic patients consented to transiliac bone biopsy following double tetracycline labelling.RESULTSOsteoporosis was present at the lumbar spine in eight patients, femoral neck in seven patients and was present at one or more sites in 13 patients (41%). Seven patients (22%) had vertebral fractures which were asymptomatic in five patients. Secondary hyperparathyroidism was present in 16 patients (53%) but significant renal failure (creatinine clearance < 70 ml/min) was only found in 8 (50%). Levels of biochemical markers of bone turnover were increased in 23 patients (72%). Serum osteocalcin (P = 0.02) and alkaline phosphatase (P = 0.04) were significantly higher in osteoporotic patients than in nonosteoporotic patients. Histomorphometric findings varied markedly between patients. Microscopic features of hyperparathyroidism were not observed.CONCLUSIONSOsteoporosis and asymptomatic vertebral fractures are common following cardiac transplantation. Biochemical markers of bone turnover were increased in the majority of patients. Many had biochemical evidence of secondary hyperparathyroidism but this could be attributable to significant renal failure in only 50% of cases. Osteocalcin and alkaline phosphatase correlated inversely with bone density. Histomorphometric findings did not correlate with these biochemical changes in most cases. These results suggest that multiple factors are responsible for osteoporosis in cardiac transplant recipients. Osteocalcin and alkaline phosphatase may be useful biochemical markers, predicting patients at highest risk of fracture.
The HLA–DQ associations with Graves' disease in Chinese children
Authors: K. Wong Gary W. , Cheng  , Dorman  
Published: March 2003

OBJECTIVEGraves' disease has been documented to be associated with different HLA genes in Caucasians and Chinese adults. The incidence of childhood Graves' disease has been reported to be high in Hong Kong Chinese. The aims of this study were to examine the HLA‐DQA1 and DQB1 associations with Graves' disease in Chinese children.PATIENTS AND DESIGNSixty‐seven Chinese children with Graves' disease (59 girls and 8 boys) and 51 racially matched healthy controls were recruited for the study. Genomic DNA was extracted from venous blood samples. HLA‐DQ typings were determined by sequence‐specific oligonucleotide probing of the respective enzymatically amplified gene. Frequencies of HLA‐DQ alleles at each locus were compared between patients and controls using the χ2‐test.RESULTSThe frequency of HLA‐DQB1*0303 was increased in the combined male and female patient group [53.7%; relative risk (RR) = 4.22; Pc = 0.005] and female patients (50.8%; RR = 3.76; Pc = 0.018) compared with that in the entire control group (21.2%). HLA‐DQB1*201 was protective for Graves' disease (10.4%; RR = 0.20; Pc = 0.006). In contrast to studies in Caucasians, DQA1*0501 was not associated with susceptibility for Graves' disease in Chinese children.CONCLUSIONSThis study confirms that DQB1*0303 is a race‐specific susceptible allele for Graves' disease in Chinese. Both susceptible and protective HLA‐DQ alleles for Graves' disease in Chinese children are different from those in Caucasians.
Evaluation of adrenal function in patients with hypothalamic and pituitary disorders: comparison of serum cortisol, urinary free cortisol and the human‐corticotrophin releasing hormone test with the insulin tolerance test
Authors: Dullaart Robin P. F. , Pasterkamp Susanne H. , Beentjes John A. M. , Sluiter Wim J. 
Published: March 2003

OBJECTIVEThis study aimed to evaluate the performance of screening tests (serum cortisol and 24‐h urinary free cortisol) and the human‐corticotrophin releasing hormone (h‐CRH) test in the assessment of adrenal function in patients with hypothalamic‐pituitary disorders.DESIGNSummary receiver operating characteristics (SROC) curve analysis was applied with the insulin tolerance test (ITT) as reference test. A peak serum cortisol response to ITT ≥ 500 nmol/l indicated adrenal sufficiency. The sensitivity at the intersect of the diagonal between sensitivity = 1 and (1 − specificity) = 1 with the SROC curve, where sensitivity and specificity are equal, and the corresponding weighted kappa, an estimate of agreement with the ITT, served as parameters of test performance. The diagnostic yield, representing the proportion of tests obviating the need for an ITT, was also calculated.MEASUREMENTSSerum cortisol at 0800 h (n = 122), at 1600 h (n = 116), 24‐h urinary free cortisol (n = 115) and the peak serum cortisol to h‐CRH (n = 129) were compared with the peak serum cortisol to ITT.PATIENTSEighty patients with hypothalamic‐pituitary disorders in whom 75 ITT's were performed pre‐ and 57 post‐operatively.RESULTSSensitivity at the intersect and weighted kappa were higher for 0800 h serum cortisol (0.873 and 0.763 respectively) than for 1600 h serum cortisol (0.769 and 0.561) and 24‐h urinary free cortisol (0.777 and 0.576). These parameters were 0.868 and 0.756 for the h‐CRH test. The diagnostic yield was 63.9% for 0800 h serum cortisol compared to 25.9% for 1600 h serum cortisol (P<10−8), 23.5% for 24‐h urinary free cortisol (P<10−8) and 60.5% for the h‐CRH test (NS).CONCLUSIONSSerum cortisol measurement at 0800 h is better than 1600 h and 24‐h urinary free cortisol to evaluate adrenal function in this patient category. The diagnostic applicability of the h‐CRH test is not superior to 0800 h serum cortisol measurement.