bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome
Authors: Conway Gerard S. , Conway Emily , Walker Caroline , Hoppner  , Gromoll  , Simoni  
Published: March 2003

OBJECTIVETo determine whether mutations in the FSH receptor gene are associated with premature ovarian failure (POF) or resistant ovary syndrome (ROS) in women in the UK. To determine whether an allelic variant of the FSH receptor gene affects fertility parameters in women with polycystic ovary syndrome (PCOS).DESIGNA mutation screen using DNA from women with POF and ROS. Restriction digest of amplified DNA from women with POF, ROS, PCOS and controls to determine allelic variant status. Fertility parameters were compared between allelic variant subgroups of women with PCOS.PATIENTSThe study population comprised 49 women with POF, 5 with ROS, 93 with PCOS and 51 controls.MEASUREMENTSIn women with PCOS, fertility and menstrual status was recorded and serum FSH and ovarian volume were measured.RESULTSNo mutation of the FSH receptor gene was found in women with POF or ROS. The allelic variant Thr307/Ser680 was found to be similarly prevalent in all study groups. The Thr307/Ser680 variant was found to have no phenotype in terms of fertility parameters in women with PCOS.CONCLUSIONSMutations of the FSH receptor gene are rare in women with premature ovarian failure or resistant ovary syndrome in the UK. Polymorphisms of the FSH receptor gene do not appear to have pathophysiological significance with regard to ovarian function.
Vitamin D insufficiency increases bone turnover markers and enhances bone loss at the hip in patients with established vertebral osteoporosis
Authors: Sahota O. , Masud T. , San P. , Hosking D. J. 
Published: March 2003

AIMThe aim of this study was to determine whether the presence of vitamin D insufficiency increases bone turnover and enhances bone loss by examining the relationship between bone turnover markers and Bone mineral density (BMD) in vitamin D insufficient and vitamin D sufficient patients, with established vertebral osteoporosis.SUBJECTS119 consecutive, active, community dwelling, elderly women were assessed over a 7‐month period between the months of March to October.RESULTSThere was a significant correlation between parathyroid hormone (PTH) and 25 hydroxyvitamin D (25(OH)D), r = − 0.42 (P < 0.01). The prevalence of vitamin D insufficiency was 26.9% (defined by a 25(OH)D ≥ 6.1 μg/l and ≤ 12 μg/l). This resulted in a statistically significant increase in bone turnover markers compared to the vitamin D sufficient group: bone alkaline phosphatase (P < 0.05), osteocalcin (P < 0.01), hydroxyproline (P < 0.05), free deoxypyridinoline (P < 0.05) and lower bone mineral density at the total hip (P < 0.01).CONCLUSIONSThese results show that there is a high prevalence of vitamin D insufficiency in the active community dwelling elderly with established vertebral osteoporosis presenting to clinical attention, which leads to increased bone turnover, decreased BMD at the hip and thus enhanced risk of further osteoporotic fractures in comparison with vitamin D sufficient subjects.
Growth hormone (GH) status is an independent determinant of serum levels of cholesterol and triglycerides in healthy adults
Authors: Vahl Nina , Klausen Ib , Christiansen Jens S , Jørgensen Jens O. L. 
Published: March 2003

OBJECTIVEBoth severe growth hormone (GH) deficiency in hypopituitary adults and physiological ageing are associated with an increase in fat mass, dyslipidaemia, and an increased incidence of cardiovascular disease. Ageing is also associated with a physiological decrease in spontaneous as well as stimulated GH secretion. We wished to evaluate the effects of endogenous GH status on circulating lipoproteins.DESIGNA cross‐sectional study.SUBJECTSForty‐two healthy nonobese adults of both sexes (20 M + 22 F) aged 27–59 years.MEASUREMENTSTwenty‐four hour GH secretion, arginine‐stimulated GH secretion, and fasting values of lipoproteins and triglycerides. Body composition was measured by CT‐scan and whole body DXA‐scan. VO2‐max was measured on an ergometer bicycle.RESULTSGH secretion decreased with age and was lower in males. Older subjects had more total body fat, subcutaneous abdominal fat, and intra‐abdominal fat than younger ones, and their VO2‐max was decreased. Men had more intra‐abdominal and subcutaneous abdominal fat but less total body fat than women. There was no sex difference in VO2‐max. Total cholesterol (TC) and LDL‐C (mmol/l) were higher in older than in the younger subjects (TC: 5.32 (95% CI = 0.49) vs. 4.17 (95% CI = 0.28), P < 0.001; LDL‐C: 3.66 (95% CI = 0.52) vs. 2.54 (95% CI = 0.37), P = 0.001) without sex differences. HDL‐C did not show any difference with age or between sexes. Triglycerides (mmol/l) were higher in older subjects and in males (older: 1.36 (95% CI = 0.19) vs. younger: 1.02 (95% CI = 0.20), P = 0.015; M: 1.34 (95% CI = 0.24) vs. F: 1.03 (95% CI = 0.16), P = 0.03). There was no age‐difference in lipoprotein (a), but concentrations were higher in women (M: 4.35 (2.95–8.30) vs. F: 19.40 (4.10–32.80), P = 0.03). TC, LDL‐C, and triglycerides correlated positively with age and indices of adiposity, and inversely with VO2‐max. TC, LDL‐C, and triglycerides also correlated significantly and negatively with arginine‐stimulated GH secretion (peak GH) (TC vs. peak GH (r = − 0.395, P = 0.01); LDL‐C vs. peak GH (r = − 0.365, P = 0.017); triglycerides vs. peak GH (r = − 0.386, P = 0.01)). Multiple linear regression analysis showed GH status to be an independent predictor of both TC, LDL‐C, and triglycerides.CONCLUSIONWe hypothesize that GH may exert direct effects on lipid metabolism.
Association of molecular variants of luteinizing hormone with menstrual disorders
Authors: Ramanujam L. N. , Liao W. X. , Roy A. C. , Loganath A. , Goh H. H. , Ng S. C. 
Published: March 2003

OBJECTIVELuteinizing hormone (LH) promotes ovulation and luteinization of the ovarian follicle, and stimulates steroidogenesis in the ovaries. It is known to be present in different molecular forms, and secretion of abnormal LH has been implicated in menstrual disorders and infertility. The purpose of this study was to determine any association of two recently described LH variants with menstrual disorders in Singapore Chinese women. One of these variants had Trp8 to Arg8 and Ile15 to Thr15 replacements in the LH β‐subunit, while the second variant possessed Ser102 substitution for Gly102.PATIENTSOne hundred and seventy six patients with menstrual disorders and two hundred normal ovulatory women were recruited and screened for the presence of these two LH variants.METHODSThe polymerase chain reaction (PCR) products of patients were analysed by restriction fragment length polymorphism (RFLP) and the results were compared with those of normal ovulatory women and confirmed by DNA sequencing.RESULTSTwenty one (11.9%) patients with menstrual disorders and twenty (10%) normal ovulatory women were found to carry the first variant, but its occurrence did not show any significant statistical difference between the patient and control groups (P = 0.679). However, the second variant was only detected in seven (4%) patients with menstrual disorders, and none of the normal ovulatory subjects (P = 0.005).CONCLUSIONSthe study showed that the first variant was not associated with menstrual disorders, whereas the second variant might be implicated in menstrual disorders in some Singapore Chinese women.
Enhancement of the GH responsiveness to GH releasing stimuli by lysine vasopressin in type 1 diabetic subjects
Authors: Coiro  , Volpi  , Capretti  , Speroni  , Caffarri  , Marchesi  , Chiodera  
Published: March 2003

OBJECTIVEWe tested the possibility that lysine vasopressin (LVP) changes the GH responsiveness to exogenously administered GH‐RH (at its minimal and maximal doses), clonidine (which is thought to stimulate endogenous GH‐RH release) and arginine (which is thought to inhibit somatostatin) in patients with type 1 diabetes mellitus and normal subjects.DESIGN AND PATIENTSNormal male subjects (NC) and age‐ and weight‐matched insulin‐dependent diabetic men (DM) with good metabolic control were studied. An iv bolus of LVP at a dose (15 μg/kg body weight (BW)) lower than the minimal GH releasing effective dose was injected just before the I.V. injection of the minimal effective dose of GH‐RH (0.035 μg/kg BW) in 10 NC and 10 DM, the I.V. injection of the maximal effective dose of GH‐RH (100 μg) in 7 NC and 7 DM, the I.V. infusion of arginine (30 g over 30 min) in 7 NC and 8 DM or the oral administration of clonidine (150 μg) in 7 NC and 8 DM. On different occasions, GH stimuli, LVP or normal saline were given alone to the same normal and diabetic subjects.MEASUREMENTSGH responses in the presence and absence of LVP were measured and compared within each group and between normal and diabetic groups.RESULTSLVP or normal saline administration did not modify the basal concentrations of GH in any subject. The administration of GH‐RH (at the minimal dose), arginine or clonidine alone induced significantly higher GH responses in the diabetic subjects than in the normal controls. At the maximal dose GH‐RH induced similar GH responses in normal and diabetic subjects. The simultaneous administration of LVP did not change the GH response to any challenging stimulation in the normal controls; in contrast, GH‐RH‐ (at both minimal and maximal dose), arginine‐ and clonidine‐induced GH increments were significantly enhanced by LVP in the diabetic subjects.CONCLUSIONSThese data show that in diabetic, but not in normal subjects LVP enhances the GH responsiveness to secretagogues, such as GH‐RH, clonidine and arginine, which act through three different mechanisms. These findings suggest that in diabetes mellitus, vasopressin functions as a primer for various GH responses.
Sexual dimorphism of cortisol metabolism is maintained in elderly subjects and is not oestrogen dependent
Authors: Toogood  , Taylor  , Shalet  , Monson  
Published: March 2003

OBJECTIVEThe net interconversion of inactive cortisone to active cortisol by 11β‐hydroxysteroid dehydrogenase type 1 (11βHSD1) may determine hepatic and adipose tissue exposure to glucocorticoid action. Cortisol metabolism exhibits a sexual dimorphism with an apparently lower activity of 11βHSD1 in females that, in an animal model, has been attributed to the effects of oestrogen. The aim of this study is to determine whether the sexual dimorphism of cortisol metabolism persists between post‐menopausal, oestrogen‐deficient women and elderly men.PATIENTSFifteen healthy men, aged 60.8–82.0 years, and 7 healthy women, aged 62.4–87.5 years, were studied. None of the subjects was receiving steroid medication at the time of the study. All the women were post‐menopausal and none was receiving sex steroid replacement therapy.MEASUREMENTS24‐h urine collections were taken from each patient and assayed for steroid metabolites by gas chromatography. Body composition was determined by dual energy X‐ray absorptiometry. Blood was drawn, after an overnight fast, for the determination of serum IGF‐I and IGFBP1 levels.RESULTSThe ratio of 11‐hydroxy cortisol metabolites to 11‐oxo cortisol metabolites (Fm/Em) was significantly higher in men than in women, 0.80 (0.55–1.86) vs. 0.67 (0.46–0.98) (P < 0.02), as was the ratio of allo‐tetrahydrocortisol (5α‐THF) + tetrahydrocortisol (THF)/tetrahydrocortisone (THE), 0.74 (0.37–2.08) vs. 0.40 (0.22–1.10) (P < 0.047). In the group as a whole there was a negative correlation between Fm/Em and percent body fat, r = − 0.43 (P < 0.05), and the negative relationship between cortisol and cortisone metabolite (Fm/Em) and total fat mass approached significance, r = − 0.39 (P = 0.07). These relationships were not apparent in the women when considered alone. Among the men there were negative relationships between Fm/Em and total fat mass, r = − 0.48, and Fm/Em and trunk fat mass, r = − 0.48 which approached significance (both P = 0.07). Serum IGFBP‐1 levels were not significantly different between the two sexes. There was a significant correlation between IGFBP‐1 and Fm/Em in the men, r = 0.84 (P < 0.0001) which persisted when total body fat mass, r = 0.85 (P < 0.0001) and trunk fat mass, r = 0.83 (P < 0.0001), were controlled for. This relationship was not evident among the women.CONCLUSIONThis study demonstrates that the previously described sexual dimorphism in cortisol metabolism is not dependent on oestrogen, although the possibility that oestrogen exerts a permanent modifying effect on 11β‐HSD1 gene expression during the pre‐menopausal period cannot be excluded. The findings confirm the primary importance of body fat as a determinant of cortisol–cortisone conversion.
Parathyroidectomy for primary hyperparathyroidism induces positive uncoupling and increases bone mineral density in cancellous bones
Authors: Abe  , Ejima  , Fujiyama  , Kiriyama  , Ide  , Sera  , Tominaga  , Ashizawa  , Yokoyama  , Eguchi  
Published: March 2003

OBJECTIVEOsteopenia is an important feature of primary hyperparathyroidism (PHP). However, little is known about the change of bone mineral density (BMD) in PHP after surgery. The aim was to investigate the mechanisms of increased BMD after parathyroidectomy in patients with PHP.DESIGNProspective observational study.PATIENTSTen patients with PHP (7 women, 3 men; mean age 53.2±9.1 years). All patients underwent parathyroidectomy for excision of parathyroid adenoma.MEASUREMENTSBMDs of two cancellous bone‐rich sites (L2‐L4 lumbar spine and ultra‐distal end of the radius, RUD) and one cortical bone‐rich site (distal third of the radius, R33%) were measured using dual energy X‐ray absorptiometry, before, and 3, 6 and 12 months after surgery. Serum intact PTH, intact osteocalcin, bone type alkaline phosphatase (b‐ALP), alkaline phosphatase, calcium, and urinary deoxypyridinoline (Dpd) were measured before, and 1 and 3 days, and 1, 2, 3, 4, 6, 8, 12, and 24 weeks after surgery.RESULTSParathyroidectomy resulted in a significant increase in BMDs of L2‐L4 and RUD at 3 months postoperatively. Urinary Dpd levels decreased within a few days after surgery, while b‐ALP and osteocalcin decreased more slowly throughout the first few months after surgery. The ratio of osteocalcin/Dpd at 1 week after surgery correlated significantly with the percentage change in BMD of L2‐L4 at 3 and 6 months after surgery. The ratio of osteocalcin/Dpd at 2 weeks correlated significantly with the percentage change in BMD of L2‐L4 at 3, 6 and 12 months after surgery. The preoperative values of osteocalcin, b‐ALP, PTH and calcium were positively correlated with the change in BMD of RUD at 3 months and L2‐L4 at 12 months, RUD at 6 months, RUD at 3 months and L2‐L4 at 12 months, respectively.CONCLUSIONSIn primary hyperparathyroidism patients, the major increase in bone mineral density following parathyroidectomy occurs within 3 months. Parathyroidectomy resulted in a marked increase in bone mineral density of cancellous bones compared to that of cortical bones. The early increase in bone mineral density was due to a preferential activation of bone formation over bone resorption as evidenced by changes in bone metabolic markers. Our results also showed that the preoperative levels of bone metabolic markers may predict the gain in bone mineral density after parathyroidectomy.
A longitudinal study on bone mineral density until adulthood in girls with Turner's syndrome participating in a growth hormone injection frequency‐response trial
Authors: Sas Theo C. , De Muinck Keizer‐Schrama Sabine M. , Stijnen Theo , Asarfi Anjalie , Van Leeuwen Wibeke J. , Van Teunenbroek Arne , Van Rijn Rick R. , Drop Stenvert L. ,   the Dutch Advisory group on Growth Hormone
Published: March 2003

OBJECTIVEThe aim of this study was to assess the volumetric bone mineral density (BMD) in girls with Turner's syndrome (TS) before and during growth hormone (GH) treatment in combination with low dose oestrogens as well as three years after discontinuation of GH treatment.DESIGNIn a prospective, randomized injection frequency‐response study, the effect of GH treatment in combination with low dose ethinyl oestradiol (starting with 0.05 μg/kg/day), on BMD was evaluated, comparing twice daily (BID) with once daily (OD) injections of a total GH dose of 6 IU/m2/day until adult height was reached. After discontinuation of GH treatment, the dosage of oestrogens was further increased to adult supplementation levels.PATIENTSNineteen untreated girls with TS, mean (SD) baseline pretreatment age 13.3 (1.7) (range 11.0–17.6) year.MEASUREMENTSBefore and during GH treatment, measurements of volumetric BMD were performed using phalangeal radiographic absorptiometry. In addition, the BMD measurements were repeated three years after discontinuation of GH treatment. BMD results were adjusted for bone age and sex, and expressed as SD‐scores (SDS) using reference values of healthy Dutch girls.RESULTSAt baseline, most individual BMD values of cortical bone as well as those of trabecular bone were within the normal range of healthy girls. However, the mean BMD SDS of the trabecular bone was significantly lower than zero. During treatment, the BMD SDS showed a significant increment to values equal or higher than zero after mean (SD) GH treatment period of 36.6 (7.5) months. The increase in BMD of the cortical bone was significantly higher in the OD group than in the BID group. The BMD SDS in the last year of GH treatment was not significant different between the two injection frequency groups. Three years after discontinuation of GH treatment, the BMD values had increased further similar as in healthy girls, resulting in BMD values all within normal range or even higher.CONCLUSIONSMost untreated girls with Turner syndrome, age ≥ 11 years, have a normal volumetric BMD of the cortical, as well as of the trabecular bone compared to healthy girls. During GH treatment with 6 IU/m2/day in combination with low dose oestrogens, the BMD SDS increases significantly. After discontinuation of GH treatment and the use of oestrogens in an adult dosage, the BMD was as high as in young healthy women.
Assessment of disease activity in Graves' ophthalmopathy by orbital ultrasonography and clinical parameters
Authors: Gerding Martin N. , Prummel Mark F. , Wiersinga Wilmar M. 
Published: March 2003

OBJECTIVETo study if A‐mode ultrasonography (US) in combination with the Clinical Activity Score (CAS) and duration of Graves' ophthalmopathy (GO) could predict the response to immunosuppression in Graves' ophthalmopathy.DESIGNA prospective clinical study.PATIENTS AND METHODSFifty‐six consecutive patients with moderately severe GO were treated with retrobulbar irradiation (10 fractions of 2 Gy). Before treatment the internal reflectivity in the extraocular eye muscles, the CAS, and the duration of Graves' ophthalmopathy were assessed and related to the therapeutic outcome 26 weeks after irradiation.RESULTSTwenty‐eight (50%) of the patients responded favourably to radiotherapy (four patients became worse, and 24 did not change), and the eye muscle echogenecity indeed tended to be lower in the responders than in the non‐responders (P = 0.09). From a receiver operator characteristics curve, a cut‐off value of 30% yielded a good positive predictive value of 85%, but the negative predictive value was only 60%. The CAS (≥ 4/10) had a positive predictive value of 65%, and a negative predictive value of 56%. When combining the ultrasound with the CAS, the positive predictive value increased to 74% and the negative predictive value to 72%. Adding the duration of eye symptoms (cut‐off 18 months), the prediction of response further improved: positive predictive value 79%, and negative predictive value 89%.CONCLUSIONSA‐mode ultrasonography has a rather good positive predictive value, but its poor negative predictive value precludes its use as sole activity parameter. By adding the Clinical Activity Score and duration of Graves' ophthalmopathy, the negative predictive value increased considerably. By using this combination, inactive disease can be identified more precise, permitting rehabilitative surgery at an earlier stage in these patients.
Lack of relationship between 11β‐hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients*
Authors: Kerstens M. N. , Riemens S. C. , Sluiter W. J. , Pratt J. J. , Wolthers B. G. , Dullaart R. P. F. 
Published: March 2003

SummaryOBJECTIVES To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11β‐hydroxysteroid dehydrogenase (11βHSD) mediated cortisol to cortisone Inter‐conversion towards cortisol, and to evaluate whether changes in insulin sensitivity induced by antecedent hyperinsulinaemia are related to changes in the 11βHSD setpoint.PATIENTS AND MEASUREMENTS The urinary ratio of (tetrahydrocortisol + allo‐tetrahydrocortisol)/petrahydrocortisone ((THF + allo‐THF)/THE) and of free cortisol/ free cortisone (UFFNFE), as well as the plasma cortisol/ cortisone ratio were measured in 8 male type 2 diabetic patients and 8 healthy male subjects without and after 24 h of insulin infusion. Insulin was infused at a rate of 30 mU/kg/h with blood glucose being clamped at euglycaemic levels in healthy subjects and at isoglycaemic levels in diabetic patients. Insulin sensitivity was assessed by measurement of whole body glucose uptake (M‐value) during a 3–4h euglycaemic clamp, directly after the 24h insulin infusion and compared to the M‐value on a control day, at least 1 week apart from the 24 h insulin infusion.RESULTS Despite impaired insulin sensitivity (M‐value, 11.6 ± 7.7 vs. 28.5 ± 11.6μmol/kg/minutes, in type 2 diabetic and healthy subjects, respectively, P<0.05), urinary (THF+ allo‐THF)/THE ratio and baseline plasma cortisol/cortisone ratio at 0800h were similar In type 2 diabetic patients (0.82 ±.0.07 and 3.77 ± 0.70, respectively) and healthy subjects (0.76±0.14 and 3.81±0.88, respectively, ns). Insulin sensitivity was not correlated with urinary (THF + allo‐THF)/VHE ratio nor with baseline plasma cortisol/ cortisone. In type 2 diabetic patients, insulin sensitivity was further Impaired by antecedent hyperinsulinaemia (P<0.05), but the urinary (THF+ allo‐THF)TTHE ratio (0.80±0.14, ns) and the plasma cortisol/cortisone at 0800h (3.66 ± 0.72, ns) did not change. In healthy subjects, insulin sensitivity did not change significantly (M‐value, 22.5 ± 9.7μmol/kg/minutes, ns), although the urinary (THF+ allo‐THF)/THE ratio (0.92±0.25, P<0.05) and the plasma cortisol/cortisone (4.59±0.63, P<0.05) increased. Insulin did not affect the UFF/UFE ratio in either group.CONCLUSION The present study does not support the hypothesis that insulin resistance in type 2 diabetes mellitus Is associated with an overall change in the 11βHSD set point towards cortisol. In view of the stimulatory effects of insulin and cortisol on adipogenesis, long‐term stimulation of 11βHSD reductase activity by insulin could aggravate visceral obesity.