bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary glycosylated, free and total pyridinoline and free and total deoxypyridinoline in diabetes mellitus
Authors: Cloos  , Wahl  , Hasslacher  , Traber  , Kistner  , Jurkuhn  , Schmidt‐Gayk  
Published: March 2003

OBJECTIVEPublished data on bone metabolism in diabetes mellitus are conflicting. We have measured pyridinium crosslinks, biochemical markers of bone resorption, in order to evaluate bone resorption in diabetes mellitus. We also wished to investigate whether, as a consequence of chronic hyperglycaemia, pyridinoline is glycosylated to a greater extent in patients with diabetes mellitus.DESIGN AND PATIENTSThis cross sectional study included 142 patients (64 males, 78 females) with insulin dependent and non‐insulin dependent diabetes mellitus (IDDM and NIDDM). These patients were compared to a healthy control group of 99 individuals (39 males and 60 females).MEASUREMENTSPyridinium crosslinks, glycosylated, free and total pyridinoline (gPYD, fPYD, tPYD) and free and total deoxypyridinoline (fDPD, tDPD) were measured in a spot urine sample by high performance liquid chromatography (HPLC). Urinary creatinine, albumin and glucose were also measured.RESULTSIn the diabetic group, values of urinary gPYD and tDPD were significantly lower than in controls. gPYD excretion was lowest in patients with severe glycosuria. Free pyridinium crosslinks, both fPYD and fDPD, were excreted to a significantly lower extent. The molar ratio of tPYD to tDPD was significantly increased in diabetes mellitus.CONCLUSIONSDecreased excretion of tDPD suggests low bone resorption in IDDM and NIDDM. Pyridinoline is not glycosylated to a greater extent in diabetes mellitus and tends to be decreased in proportion to the degree of glycosuria. Excretion of gPYD, fPYD and fDPD is depressed in severe glycosuria. Diminished degradation to the final products, fPYD and fDPD, might represent increased resistance to enzymatic activity or diminished enzymatic activity. The increased molar ratio tPYD/tDPD in urine suggests an increased ratio in bone collagen in diabetes mellitus.
Serum substances that interfere with thyroid hormone assays in patients with chronic renal failure
Authors: Iitaka Makoto , Kawasaki Satomi , Sakurai Shin‐ichi , Hara Yoshihito , Kuriyama Renjiro , Yamanaka Kayo , Kitahama Shinji , Miura Shiro , Kawakami Yoshito , Katayama Shigehiro 
Published: March 2003

OBJECTIVESerum thyroid hormone concen_trations in patients with chronic renal failure are usually low, despite normal serum TSH levels. We investigated the effect on thyroid hormone assays of serum dialysable organic acids that are elevated in uraemic patients.PATIENTSSerum samples from 42 patients with chronic renal failure who were receiving haemodialysis and 37 sex‐ and age‐matched healthy subjects were examined.DESIGN AND MEASUREMENTSSerum thyroid hormone concen_trations were measured with an analogue radioimmunoassay (RIA), a labelled antibody assay, and an equilibrium dialysis/RIA method. Serum concen_trations of organic acids were determined with high performance liquid chromatography.RESULTSSerum thyroid hormone levels determined by an analogue RIA and a labelled antibody assay in uraemic patients increased, and serum concen_trations of organic acids decreased following haemodialysis. A significant association existed between serum free T3 (FT3) levels determined by an analogue RIA and serum concen_trations of indoxyl sulphate (IS) prior to dialysis. There was also a significant association between serum free T4 (FT4) levels determined by an analogue RIA and serum concen_tration of IS and hippuric acid (HA) prior to dialysis. There was a significant association between the changes of serum concen_trations of indole acetic acid (IAA) and FT4 concen_trations prior to and following haemodialysis when determined by an analogue RIA. Serum FT3 and FT4 levels significantly decreased after the addition of IS to serum from healthy subjects when determined by an analogue RIA but not by a labelled antibody assay. Serum FT4 levels, but not FT3 levels, decreased after addition of IAA when determined by an analogue RIA. Serum FT4 concen_trations determined by an equilibrium dialysis/RIA were significantly higher than those determined by the other two methods. The addition of IS, IAA, and HA to serum samples from healthy subjects significantly increased FT4 concen_trations when determined by an equilibrium dialysis/RIA method.CONCLUSIONSIncreased serum levels of indoxyl sulphate, indole acetic acid and hippuric acid in sera of uraemic patients may interfere with thyroid hormone measurements when an analogue radioimmunoassay is used. In contrast, there was little interference with a labelled antibody assay. Dialysable organic acids may also interfere with thyroid hormone assays determined by an equilibrium dialysis/radioimmunoassay method.
A population‐based study of Graves' disease in Danish twins
Authors: Heiberg Brix Thomas , Christensen Kaare , Holm Niels V. , Harvald Bent , Hegedüs Laszlo 
Published: March 2003

OBJECTIVEThe aetiology of Graves' disease (GD) is generally thought to fit a multi‐factorial pattern of inheritance in which clinical disease develops on the basis of genetic susceptibility interacting with environmental and endogenous factors. In previous twin studies the probandwise concordance rates for hyperthyroidism were as high as 0.86 in monozygotic twins and 0.20 in dizygotic twins, indicating a very strong genetic influence. In these studies, however, no effort was made to distinguish between GD and non‐autoimmune hyperthyroidism, and one study also included patients with simple non‐toxic goitre, hampering if not invalidating any conclusions. The aim of the present study was to determine whether there is a genetic contribution in the aetiology of GD.DESIGNHistorical cohort study of pairs of same‐sex twins, with information on GD being gathered by questionnaire surveys in the 1950s and 1960s. All available hospital material was sought to veriify the diagnosis, which was assigned on the basis of clinical and histopathological evidence. The healthy co‐twins were followed through middle age by questionnaire surveys in the 1970s and 1980s.PATIENTSSame‐sex twin individuals born between 1870–1920, included in a population‐based nationwide register. A total of 118 subjects indicated hospitalization due to GD. A hospital record was available in 76 subjects. Of these, 55 (46 females and 9 males) could be classified as having GD.MEASUREMENTSPairwise and probandwise concordance rates for GD in monozygotic and dizygotic twin pairs.RESULTSThe probandwise concordance rates were 0.36 for monozygotic pairs and 0 for dizygotic pairs. The pairwise concordance rates were 0.22 and 0 for monozygotic and dizygotic pairs, respectively. The concordance rates were significantly (P = 0.012) higher in monozygotic than in dizygotic pairs.CONCLUSIONSThese results confirm that genetic factors play an important role in the aetiology of Graves' disease. However, they may not be as powerful as previously thought.
Effectiveness of chronic treatment with alendronate in the osteoporosis of Cushing's disease
Authors: Di Somma Carolina , Colao Annamaria , Pivonello Rosario , Klain Michele , Faggiano Antongiulio , Tripodi Francesca S. , Merola Bartolomeo , Salvatore Marco , Lombardi Gaetano 
Published: March 2003

BACKGROUNDOsteoporosis is common in patients with Cushing's disease and is likely due to an imbalance between bone formation and resorption. Alendronate is an aminobisphosphonate that is able to increase bone mass mainly by inhibiting bone resorption.OBJECTIVEWe have evaluated the effect of chronic treatment with alendronate on bone mineral density (BMD) in patients with Cushing's disease.PATIENTS39 patients with Cushing's disease entered this study. 39 age‐, sex‐ and BMI‐matched normals served as controls for baseline evaluation. The 39 patients were divided into four groups: 1) 10 patients with active disease treated with alendronate and ketoconazole; 2) 11 patients with inactive disease treated with alendronate; 3) 8 patients with active disease treated with ketoconazole alone, 4) 10 patients with inactive disease received no treatment.TREATMENT PROTOCOLAlendronate was given for 12 months in a dose of 10 mg orally once daily after fasting at 0800 h in the morning. Ketoconazole was given in a dose of 200–600 mg orally daily, when pituitary surgery was unsuccessful.STUDY DESIGNLumbar spine (L1–L4) and femoral neck BMD, serum osteocalcin (OC), urinary cross‐linked N‐telopeptides of type I collagen (Ntx) levels were evaluated at study entry, in patients and controls, and were repeated after 6 and 12 months in the 39 patients.RESULTSBMD values were lower in patients with Cushing's disease than in controls at both L1–L4 (0.72 ± 0.4 vs. 1.01 ± 0.6 g/cm2, P < 0.05) and femoral neck (0.69 ± 0.3 vs. 0.96 ± 0.6 g/cm2, P < 0.05). In the 39 patients with Cushing's disease considered as a whole, serum OC levels were lower (1.1 ± 0.1 vs 1.5 ± 0.1 nmol/l, P < 0.01), while Ntx values were higher than in controls (168 ± 25 vs. 61 ± 31 nmol BCE/mmol creatinine, P < 0.01). In the alendronate‐treated groups, serum OC levels increased, while Ntx levels significantly decreased after 6 and 12 months of treatment without any significant difference between the two groups. BMD values measured at L1–L4 and femoral neck significantly increased after 12 months of therapy. In patients of group 4, a significant increase of serum OC levels and a significant decrease of Ntx levels were observed together with a slight increase of BMD values after 12 months. No significant change in either biochemical markers or BMD values was found in patients of group 3.CONCLUSIONSPatients with Cushing's disease have osteoporosis which needs to be rapidly reversed to limit the risk of fracture. The results of the present study show that a 12 month treatment period with alendronate induced an improvement in bone mineral density greater than in untreated patients.
The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site
Authors: Kottler Marie‐Laure , Seret‐Bégué Dominique , Lahlou Najiba , Assayag Michel , Carré Marie‐Claude , Lagarde Jean‐Pierre , Ajzenberg Christiane , Christin‐Maitre Sophie , Bouchard Philippe , Mikol Jacqueline , Counis Raymond , Warnet André 
Published: March 2003

OBJECTIVEGiven the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours.DESIGNWe determined if GnRHR mRNA was expressed in gonadotroph tumours using RT‐PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of α, β‐FSH and β‐LH subunit (SU) genesSUBJECTSRNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry ( >10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high α‐SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects.RESULTSWe found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 α‐secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for β‐FSH (P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker.CONCLUSIONThe GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.
Serum leptin and insulin concentrations in prepubertal lean, obese and insulin‐dependent diabetes mellitus children
Authors: Kamoda Tomohiro , Saitoh Hisako , Nakahara Satoko , Izumi Ishou , Hirano Takeki , Matsui Akira 
Published: March 2003

OBJECTIVETo evaluate the relationship between serum levels of leptin and insulin in prepubertal lean, obese and insulin‐dependent diabetes mellitus (IDDM) children.SUBJECTS AND MEASUREMENTSPrepubertal children, 16 lean, 17 obese and 16 IDDM were included in the study. Fastang serum leptin and insulin concentrations were measured by radioimmunoassays.RESULTSThe serum level of leptin was significantly higher in obese children than in lean and IDDM children (P < 0.0001 and P < 0.0001, respectively), and showed a positive correlation with body mass index (BMI) for the combined group (lean, obese and IDDM; r = 0.77, P < 0.0001). In addition, the serum leptin level was higher in IDDM children than in lean controls (P < 0.01), whereas no difference was found in BMI between the two groups. The mean fasting serum levels of insulin were significantly elevated in IDDM children as compared with lean controls (P < 0.01). A significant positive correlation was found between serum insulin and leptin levels for the combined group (r = 0.37, P < 0.01). When a multiple regression analysis for all subjects was performed, the total contribution of all parameters, including gender, BMI and log insulin, accounted for 75% of the leptin variation. BMI (57.8%), log insulin (14.0%) and gender (3.2%) contributed significantly to this variation.CONCLUSIONSThe elevated concentration of leptin in insulin‐dependent diabetic children, independent of body mass index, was probably caused by chronically increased serum insulin levels. We demonstrated that not only body mass index but also insulin was a significant independent predictor of serum leptin concentrations. It is therefore suggested that insulin might play an important role in regulating serum leptin concentrations independent of adiposity.
Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic‐pituitary disorders
Authors: Clark  , Neylon  , Raggatt  , Sheppard  , Stewart  
Published: March 2003

OBJECTIVETo define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic‐pituitary disorders.DESIGN AND PATIENTSThe cortisol response to 250 μg im ACTH1–24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post‐ACTH cortisol results were also determined using the four immunoassays.RESULTSThe distribution of cortisol results at all time points and for all methods were non‐Gaussian and significant differences in the absolute values of the 5th–95th percentiles were found between methods (P < 0.01). At 30 min post‐Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post‐ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min.CONCLUSIONSThe definition of the ‘normal’ response to Synacthen should be both gender and method related at all time points. The data suggest that up to one‐third of untreated patients with pituitary disease may have subtle defects in the hypothalamic‐pituitary‐adrenal axis.
Growth in children with craniopharyngioma following surgery
Authors: Tiulpakov A. N. , Mazerkina N. A. , Brook C. G. D. , Hindmarsh P. C. , Peterkova V. A. , Gorelyshev S. K. 
Published: March 2003

OBJECTIVEHypopituitarism, including severe GH deficiency, is an almost inevitable outcome of craniopharyngioma. However, some GH deficient children with this tumour may grow normally or even have accelerated growth postoperatively. To study this phenomenon we have investigated the endocrine status, including IGF‐1 and its binding proteins IGFBP‐1 and IGFBP3, in children referred for follow‐up at various time intervals after surgery.PATIENTSTwenty‐five patients (14 boys and 11 girls, aged 3.8–18.9 years), were studied on 34 occasions between 0.5 to 10.8 years after surgery. The tumour was intrasellar in 11 cases and suprasellar in 14.METHODSHeight and height velocity were recorded as SDS values. Body mass index (BMI) was calculated as weight/height2. GH secretory status was evaluated by stimulation both with oral clonidine and with GH releasing hormone. Serum insulin (INS) levels were studied following an oral glucose load. IGF‐1, IGFBP‐3, IGFBP‐1 and prolactin serum concentrations were evaluated in fasting samples. All hormones were measured by radioimmunoassay.RESULTSAll patients had growth hormone (GH) deficiency. Height (HtSDSCA) and height velocity SDS for chronological age (HVSDSCA) decreased progressively after surgery (r = –0.47, P = 0.005, and r = –0.4, P = 0.032, respectively) but four patients had normal HtSDSCA 6.1 to 10.8 years following their first surgery.There was a significant correlation between BMI and HtSDSCA (r = 0.37, P = 0.03). BMI in children with suprasellar craniopharyngioma was significantly greater than that in patients with intrasellar tumour (23.3 ± 7.0 vs. 17.3 ± 1.4 kg/m2; P = 0.001). In 13 of 33 cases oral glucose load was accompanied by hyperinsulinaemia with serum INS levels greater than 50 mU/l. The mean area under the curve (AUC) of INS after glucose load (INSAUC) in the suprasellar group was greater than in the patients with intrasellar lesion (6945.5 ± 4411.8 vs. 2495.5 ± 1768.8 mU/l. min P = 0.001). The log INSAUC correlated significantly with HtSDSCA (0.37, P = 0.03). Fasting serum IGF‐1 and IGFBP3 levels were normal in 8 and 12 of the 31 measurements, respectively. Both IGF‐1SDS and IGFBP‐3SDS correlated significantly with HtSDSCA (r = 0.77, P = 0.0002 and r = 0.65, P = 0.0001, respectively) and the log INSAUC (r = 0.39, P = 0.035, r = 0.56, P = 0.002, respectively). As determined by forward stepwise regression analysis, IGF‐1SDS was the single most important predictor of HtSDSCA (R2 = 0.33, P = 0.001) in the subset mode.CONCLUSIONA few children with craniopharyngioma grew normally after surgery, in spite of being GH‐deficient. This growth phenomenon, which is usually accompanied by obesity, was more common in patients with suprasellar tumour and is likely to be associated with the effect of IGF‐1 bioavailability, which, in turn, may be modulated largely by insulin.
Comparison of the diagnostic utility of the simplified and standard i.m. glucagon stimulation test (IMGST)
Authors: Orme Stephen M. , Price Alun , Weetman Anthony P. , M. Ross Richard J. 
Published: March 2003

OBJECTIVETo compare the peak GH and cortisol responses to the simplified and standard i.m. glucagon stimulation test (IMGST) in order to determine whether the use of a simplified form of this test results in a loss of diagnostic utility.PATIENT AND DESIGNA retrospective study of 35 consecutive patients with pituitary disease who underwent a standard IMGST to measure GH (n = 34) or cortisol (n = 21) reserve at the programmed investigation unit of the Northern General Hospital, Sheffield.MEASUREMENTSCortisol, glucose and GH levels were measured at baseline and 30. 60, 90, 120, 150, 180, 210 and 240 min during the standard IMGST. We used the hormone levels at baseline, 150 and 180 min for the simplified IMGST and compared the cortisol and GH responses achieved.RESULTSThe median (range) peak GH and cortisol responses to simplified and standard IMGST were comparable 4.2 (0.5–47.5) vs 5.4 (0.5–47.5) mU/l (P = 0.75) and 635 (306–1669) vs 647 (306–1669) nmol/l (P = 0.801), respectively. Using the standard ‘cut‐off’ points to assess GH (9 mU/l) or cortisol deficiency (580 nmol/l) there was no significant loss of diagnostic utility (P = 0.98 and P = 1.00, respectively).CONCLUSIONSThe simplified and standard IMGST have a similar diagnostic utility. The simplified IMGST could replace the standard IMGST as a screening test for GH and cortisol reserve in pituitary disease. The insulin‐induced hypoglycaemia stress test can be reserved for cases in which a second assessment of pituitary reserve is clinically indicated or because of an indeterminate biochemical result.
An in vivo study of the cortisol–cortisone shuttle in subcutaneous abdominal adipose tissue
Authors: Katz J. R. , Mohamed‐Ali V. , Wood P. J. , Yudkin J. S. , Coppack S. W. 
Published: March 2003

OBJECTIVEPrevious in vitro studies have demonstrated significant 11‐beta hydroxysteroid dehydrogenase (11 β‐HSD) oxo‐reductase activity in visceral, but not subcutaneous adipose stromal cells. We have conducted an in vivo study of the cortisol–cortisone shuttle in subcutaneous abdominal adipose tissue.DESIGNWe measured arteriovenous (A‐V) differences in serum cortisol and cortisone across subcutaneous abdominal adipose tissue and forearm muscle in a heterogeneous group of subjects.PATIENTSWe studied 34 subjects (male:female = 12 : 22), age median (interquartile range) 45 (19–65) years, body mass index 32.7 (20.4–77.1) kg m−2, total body fat 34.4 (5.6–119.1) kg.MEASUREMENTSSerum cortisol and cortisone were measured in serum samples from a radial artery, superficial epigastric vein and deep forearm vein. Abdominal adipose and forearm blood flow rates were measured by 133Xenon washout and plethysmography, respectively.RESULTSFor cortisone, there was significant (P < 0.001) clearance by adipose tissue, with an A‐V difference of 4 (1–7) nmol/l. For cortisol there was a trend for arterial concentrations (203 (142–292) nmol/l) to be lower than venous (225 (152–263) nmol/l), but this was not significant. The adipose tissue cortisone clearance rate correlated with total body fat (r = 0.35, P = 0.05).CONCLUSIONSWe have demonstrated 11 β‐HSD oxo‐reductase activity in subcutaneous abdominal adipose tissue, which may be increased in obesity.