bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone mineral density in Turner's syndrome—a longitudinal study
Authors: Shaw N. J. , Rehan V. K. , Husain S. , Marshall T. , Smith C. S. 
Published: November 2003

OBJECTIVEOsteoporosis is a recognized problem in adult women with Turner's syndrome, the aetiology of which is unclear. The aim of this study was to examine bone mineralization longitudinally in a group of girls with Turner's syndrome and to study the effect of different treatments on bone mineral density.DESIGNA prospective observational study.PATIENTSEighteen girls with Turner's syndrome aged 4–17 years attending a paediatric endocrine clinic.MEASUREMENTSBone mineral density of the lumbar spine was assessed using dual energy X‐ray absorptiometry at several time points over a 2.5‐year period.RESULTSOnly one girl had evidence of a significant reduction in bone density when comparisons were made with control data related to body weight and pubertal status. No advantage was found for any form of treatment in optimizing bone mineralization.CONCLUSIONSAs there is little evidence of reduced bone mineral density in girls with Turner's syndrome there is no justification for an early introduction of oestrogen replacement during the prepubertal years.
Urinary growth hormone: a screening test for growth hormone sufficiency
Authors: Butt Debra A. , Sochett Etienne B. 
Published: November 2003

OBJECTIVESThe majority of short statured children referred for serum GH testing prove to be GH sufficient. The purpose of our study was to evaluate urinary growth hormone (uGH) as a screening test for GH sufficiency.PATIENTSWe studied (i) short statured children previously diagnosed as GH sufficient (n = 44) or GH deficient (n = 41) (peak serum GH ≥8 μg/l or <8 μg/l, respectively); (ii) short children undergoing serum GH stimulation tests (n = 23, test group); (iii) normal statured children (n = 45, control group).DESIGNThree separate overnight urine collections were obtained in all groups. GH injections in GH deficient subjects were discontinued 4 days prior to urine collection.MEASUREMENTSuGH concentrations were measured using a chemiluminescence immunoassay. Overnight uGH was expressed in several ways (overnight excretion and overnight excretion corrected for body surface area, time and creatinine). Receiver operator curves (ROC) were constructed from the data obtained in the GH sufficient and deficient subjects. Sensitivity and specificity were then determined for various urinary cut‐offs. These cutoffs were validated in turn in the test group by comparison of the predicted with the observed GH status.RESULTSThe GH deficient group had the lowest GH output with respect to overnight uGH, overnight uGH/m2, overnight uGH/h and overnight uGH/creatinine when compared with the GH sufficient and control groups (P = 0.0001). Overnight uGH/m2 data gave the greatest area under the ROC curve. At 100% specificity (no GH deficient subjects), it had the highest sensitivity, 63.6% (49.2–78.0% CI) at a cut‐off of 2.3 ng/m2 (63.6% of GH sufficient subjects had uGH levels >2.3 ng/m2). When this and other cut‐offs were applied to the test group, we found consistency between the observed and predicted numbers of GH sufficient and deficient subjects.CONCLUSIONSWe conclude that urinary GH is a useful test for the diagnosis of GH sufficiency as defined by serum criteria and can be used to reduce significantly the number of serum stimulation tests.
Anti‐GAD65 autoantibody in Taiwanese patients with insulin‐dependent diabetes mellitus: effect of HLA on anti‐GAD65 positivity and clinical characteristics
Authors: Chuang Lee‐Ming , Lin Chun‐Yin , Wu Huey‐Peir , Tsai Wen‐Yu , Tai Tong‐Yuan , Lin Boniface J. 
Published: November 2003

OBJECTIVEAnti‐GAD65 antibody has been studied widely in patients with insulin‐dependent diabetes mellitus (IDDM) in many different populations. However, the prevalence of GAD65 autoantibody has not been assessed in Taiwanese patients with IDDM. We therefore characterized GAD65 antibody and investigated the effect of HLA‐DR phenotypes on GAD65 autoimmunity and other clinical characteristics in Taiwanese subjects with IDDM.SUBJECTS AND MEASUREMENTSTwo hundred and twenty‐five patients (male 102, female 123) with IDDM were recruited. The diagnostic criteria for IDDM were age of onset before 30 years, presence of diabetic ketoacidosis, and insulin‐dependency within 3 years of onset. We employed a radioligand method to detect GAD65 antibody. HLA‐DR typing was performed by the PCR‐SSO techniques. Plasma C‐peptide and antithyroid microsomal antibody were also measured.RESULTSThe prevalence of GAD65 antibody according to duration of disease were 50/91 (54.9%), 37/95 (38.9%), 8/24 (33%), and 3/15 (20%) among the groups of duration ≤5, 6–10, 11–15, and >15 years, respectively (p = 0.0011). There were no significant differences between GAD(+) and GAD(−) patients in age of onset (11.5 ± 6.5 and 11.6 ± 13.4 years, respectively), gender distribution (male:female 39:59 and 58:69, respectively) and percentage with residual β cell function (38.8% and 29.1%, respectively). Multiple regression analysis revealed that duration of IDDM correlated inversely with residual β cell function. Earlier onset of IDDM correlated with a loss of β cell function and a HLA‐DR phenotype containing DR3/4, DR3/3 or DR3/9.CONCLUSIONSPrevalence of GAD65 autoantibody among Taiwanese subjects with IDDM was negatively correlated with duration of disease. Different determinants in the HLA‐DR locus contributed to the clinical onset of IDDM but not to GAD autoimmunity.
Abnormal melatonin secretion in hypogonadal men: the effect of testosterone treatment
Authors: Luboshitzky Rafael , Wagner Oded , Lavi Shachar , Herer Paula , Lavie Peretz 
Published: November 2003

OBJECTIVEWe have recently demonstrated that GnRH deficient male patients have increased nocturnal melatonin secretion, whereas hypergonadotrophic hypogonadal males have decreased melatonin levels. We were interested in determining whether testosterone (T) treatment (when T levels were well matched with pubertal control values) has an effect on melatonin secretory profiles in these patients.DESIGNProspective, controlled.SUBJECTSSix male patients with idiopathic hypogonadotrophic hypogonadism (IGD), six males with hypergonadotrophic hypogonadism due to Klinefelter's syndrome (KS) and seven controls. Patients were examined before and during the administration of 250 mg testosterone enanthate/month for four months.MEASUREMENTSSerum samples for melatonin levels were obtained every 15 minutes from 1900 to 0700 h in a controlled light‐dark environment. The results of FSH, LH, T and oestradiol (E2) (determined at hourly intervals) and melatonin profiles, were compared with the pre‐treatment values in each group, and with values obtained in the control group.RESULTSAll 12 patients had low pre‐treatment T levels (1.4 ± 0.7 in IGD and 2.0 ± 0.4 in KS vs. 19.8 ±  2.3 nmol/l in controls) and attained normal levels after four months of T treatment (19.5 ± 7 in IGD and 22.7 ±  3.8 nmol/l in KS). Serum LH, FSH and E2 levels (11 ± 4 IU/l, 24 ± 10 IU/l and 113 ± 12 pmol/l, respectively) were still elevated in KS during T treatment as compared with values in controls (2 ± 1 IU/l, 2 ± 1 IU/l and 67 ± 4 pmol/l, respectively). In IGD, serum LH (0.12 ± 0.1 IU/l) and FSH (0.16 ± 0.2 IU/l) levels during T treatment were suppressed. Pretreatment melatonin levels in IGD were greater than those in age‐matched pubertal controls while in KS, melatonin levels were lower than values in controls. Melatonin levels were equal in all 12 hypogonadal patients and controls when T levels were well matched. Mean (±SD) dark‐time melatonin levels decreased from 286 ± 18 to 157 ± 26 pmol/l in IGD and increased from 92 ± 19 to 183 ± 48 pmol/l in KS (vs 178 ± 59 pmol/l in controls). The integrated melatonin values decreased in IGD (from 184 ± 14 to 102 ± 21 pmol/min. l × 103) and increased in KS (from 64 ± 13 to 123 ± 40, vs. 116 ± 39 pmol/min. l × 103 in controls). No correlations were found between melatonin and LH, FSH or E2 levels.CONCLUSIONSThese data indicate that male patients with GnRH deficiency have increased nocturnal melatonin secretion while in hypergonadotrophic hypogonadal males melatonin secretion is decreased. Testosterone treatment normalized melatonin concentrations in these patients. Taken together, the results suggest that GnRH, gonadotrophins and gonadal steroids modulate pineal melatonin in humans.
Absence of mutations in exon 3 of the GnRH receptor in human gonadotroph adenomas
Authors: Kaye P. V. , Hapgood J. , Millar R. P. 
Published: November 2003

BACKGROUND AND OBJECTIVEThe mechanisms of tumourogenesis for the majority of pituitary tumours are unknown. Mutations of G‐protein coupled receptors (GPCRs) have recently been described as important in diverse human diseases, including thyroid adenomas. To test this hypothesis in pituitary gonadotroph adenomas, we amplified and sequenced the GnRH receptor gene in 12 human tumours. We restricted our analysis to the third exon, since this represents the hotspot for activating mutations in other GPCRs.PATIENTSPituitary adenoma tissue was identified from patients who had tumours resected and where a diagnosis of gonadotroph adenoma had been made on the basis of immunohistochemical demonstration of LH and/or FSH.METHODSGenomic DNA was extracted from paraffin‐embedded tissue of 18 gonadotroph adenomas. The third exon was successfully amplified by PCR in 12 cases and directly sequenced.RESULTSWe found no missense point mutations or even silent polymorphisms in any tumour studied.CONCLUSIONWe conclude that activating mutations of the GnRH receptor gene do not represent an important mechanism of pituitary gonadotroph tumourogenesis.
The effect of an intravenous infusion of IGF‐I and insulin on IGFBP‐1, IGFBP‐3, acid labile subunit, free and bound IGF‐I, catecholamines and potassium in normal volunteers during an amino acid and glucose clamp
Authors: Russell‐Jones D. L. , Umpleby A. M. , Shojaee‐Moradie F. , Boroujerdi M. A. , Jones R. H. , Baxter R. C. , Sönksen P. H. 
Published: November 2003

OBJECTIVESTo investigate the effects of IGF‐I and insulin at doses equipotent with respect to hypoglycaemic effect on IGF‐I concentrations (free and bound), IGF binding proteins, catecholamines and potassium levels.DESIGNA glucose and amino acid clamp technique was used to investigate the effects of a 3 h intravenous infusion of either IGF‐I 43.7 pmol/kg/min (20 μg/kg/ h) or insulin 3.4 pmol/kg/min (0.5 mU/kg/min).MEASUREMENTSCirculating levels of total IGF‐I, free and bound IGF‐I, insulin, IGFBP‐1, IGFBP‐3, ALS, catecholamines and potassium were measured.PATIENTS6 normal human volunteers aged 21–49.RESULTSDuring the IGF‐I infusion, IGF‐I levels increased (P < 0.01) (26.6 ± 2.8–88.9 ± 14.2 nmol/l) and insulin levels fell (P < 0.05) (16.7 ± 2.9–7.2 ± 1.6 mu/l). During the insulin infusion, insulin levels increased (P < 0.01) (11.7 ± 1.6–56.7 ± 16 mu/l) and there was no change in IGF‐I. There was no significant change in IGFBP‐3 or ALS during the IGF‐I or insulin infusions. There was a significant (P < 0.05) fall in IGFBP‐1 levels from 27.1 ± 4.1–8.06 ± 1.6 μg/l during the insulin infusion and a significant (P < 0.05) rise during the first 120 min of IGF‐I infusion from 28.6 ± 6.3–67.9 ± 10.6 μg/l. There was a significant (P < 0.05) increase in free IGF‐I and IGF‐I bound to the 150 and 50 kD plasma fractions during the IGF‐I infusion. At basal and the end of the IGF‐I infusion adrenaline levels (pmol/l) were: 173 ± 22 and 174 ± 28; dopamine levels (pmol/l) were: 415 ± 87 and 470 ± 87; plasma potassium (mmol/l) was 4.2 ± 0.06 and 3.56 ± 0.13. At basal and the end of the insulin infusion adrenaline levels (pmol/l) were: 160 ± 38 and 163 ± 21; dopamine levels (pmol/l) were: 238 ± 26 and 316 ± 31; plasma potassium (mmol/l) was 4.2 ± 0.07 and 3.92 ± 0.17. There were no significant changes in plasma catecholamine concentrations with either infusion but potassium concentrations were significantly (P < 0.05) reduced during the IGF‐I infusion.CONCLUSIONSWe conclude that an infusion of IGF‐I resulted in increased levels of both free and bound IGF‐I. IGF‐I and insulin under conditions of adequate substrate supply have acute effects on IGFBP‐1 and potassium physiology, but have little effect on IGFBP‐3, ALS or catecholamines.
Prospective study of bone loss in pre‐ and post‐menopausal women on L‐thyroxine therapy for non‐toxic goitre
Authors: De Rosa Giovina , Testa Americo , Giacomini Denise , Carrozza Cinzia , Astazi Pietro , Caradonna Paolo 
Published: November 2003

OBJECTIVEHyperthyroidism is associated with increased bone turnover and bone resorption, but the effects of suppressive doses of thyroxine in treating non‐toxic goitre remain unclear. We carried out a longitudinal study to evaluate the effect on bone of L‐thyroxine (L‐T4) therapy in women with non‐toxic goitre.SUBJECTSForty Caucasian women, 19 of whom were pre‐menopausal and 21 post‐menopausal, were studied before and after 12 months' L‐T4 therapy for non‐toxic goitre; 40 women matched for age, body mass index and menopausal status were used as controls.DESIGNThe minimal dosage of L‐T4 (mean ± standard error = 1.5 ± 0.1 μg/kg−1 day−1) was given to each patient to obtain subnormal but detectable serum TSH (≤ 0.2 mU/l). Patients and controls were assessed for minor determinants of bone loss rate, such as genetic and behavioural factors.MEASUREMENTSBone mineral density (BMD) of the lumbar spine, femoral neck, trochanter and Ward's triangle was measured by dual‐energy X‐ray absorptiometry at baseline and 12 months; serum and urine markers of bone turnover was measured at baseline, 3, 6 and 12 months.RESULTSNo significant difference was detected in BMD values between patients and controls either at presentation or at the 12‐month follow‐up. Pre‐menopausal patients showed a significant decrease in femoral neck BMD (−1.7 ± 0.6%, P < 0.05) while controls showed no change + 0.2 ± 0.9%, P = NS). Post‐menopausal patients showed a significant decrease in BMD of the lumbar spine (−1.3 ± 0.6%, P < 0.05; controls + 0.0 ± 0.4%, P = NS), femoral neck (−1.5 ± 0.6%, P < 0.05; controls −1.2 ± 0.8%, P = NS) and trochanter (−2.1 ± 0.8%, P < 0.05; controls −1.4 ± 0.9%, P = NS). In both pre‐ and post‐menopausal patients the serum markers of bone turnover, alkaline phosphatase and osteocalcin, showed an early and progressive increase. A linear relationship was found only between the 3‐month values of serum osteocalcin and the urine hydroxyproline/creatinine ratio in both pre‐menopausal (r = 0.87, P < 0.01) and post‐menopausal (r = 0.72, P < 0.05) patients. No correlation was found between bone loss or changes in bone turnover markers and L‐T4 dose or thyroid hormone levels.CONCLUSIONThis longitudinal study suggests that TSH‐suppressive therapy with L‐thyroxine for non‐toxic goitre significantly increases the bone mineral turnover and might contribute to a BMD reduction, more marked on cortical bone, in both pre‐ and post‐menopausal women.
Acute effects of intravenous amiodarone on sulphate metabolites of thyroid hormones in arrhythmic patients
Authors: Iervasi Giorgio , Clerico Aldo , Manfredi Cristina , Sabatino Laura , Biagini Andrea , Chopra Inder J. 
Published: November 2003

OBJECTIVESFactors that contribute to the remarkably rapid decrease in serum T3 and increase in reverse T3 (rT3) levels during illness, fasting, or treatment with some drugs (e.g. amiodarone) are not clear. In order to understand better the effect of acute amiodarone administration on T3 metabolism, especially the sulphation pathway, we performed a prospective study in 8 arrhythmic in‐patients treated with a loading dose of amiodarone.DESIGNAmiodarone was administered by i.v. infusion of 20 mg/kg/day on day 1 and 10 mg/kg/day on day 2, followed by 600 mg/day orally throughout the study. Two serum samples for amiodarone and hormone assays (thyroid hormones, TSH, and the sulphate metabolites of 3′‐T1, 3,3′‐T2, and T3) were collected before the start of therapy, every 12 h during the first 3 days of amiodarone administration, and then once a day for 2–10 days.SUBJECTSEight patients (4 men and 4 women, aged 44–82 years), who were treated with amiodarone because of cardiac dysrhythmia, were enrolled in the study.RESULTSSerum concentrations of total T4 significantly increased in the last 3 days of the study (anova, P = 0.0002). However, serum total T3 progressively and significantly decreased throughout the study (anova, P < 0.0001). Serum free thyroid hormone concentrations (freeT3 and freeT4) did not significantly change during the study. Serum rT3 (anova, P < 0.0001) and TSH (anova, P = 0.0009) rapidly and progressively increased throughout the study. Starting from the first 24 h, serum concentrations of T3 sulphate (T3‐S) significantly and progressively increased from (mean ± SD) 0.057 ± 0.029 nmol/l under basal conditions to 0.089 ± 0.036 nmol/l after 5 days of amiodarone therapy (anova, P = 0.0011). Since total T3 levels progressively decreased throughout the study, the ratio of the T3‐S and total T3 values progressively increased from 4.8 ± 2.7% under basal conditions to 10.6 ± 7.3% after 5 days of amiodarone therapy (anova, repeated measures, P < 0.0001). Basal serum concentrations of sulphate metabolites of T2 (T2‐S, 2.22 ± 1.7 nmol/l) and T1 (T1‐S, 1.29 ± 0.74 nmol/l) did not significantly change throughout the study.CONCLUSIONSOur data indicate that a loading dose of intravenous amiodarone in patients with cardiac dysrhythmias is followed by a very rapid and progressive increase in circulating T3‐S levels, possibly due to an inhibition of type 1‐iodothyronine de‐iodinase. Since T2‐S and T1‐S, common final metabolites of the thyroid hormone sulphation pathways remained unchanged, our data suggest that the total amount of thyroid hormone degraded by sulphation pathways remains unaltered during amiodarone treatment. Finally our findings are compatible with the view that sulphation represents an important pathway for T3 metabolism in vivo in man.
Increase in haemoglobin concentrations in growth hormone deficient adults during human recombinant growth hormone replacement therapy
Authors: Ten Have S. M. T. H. , Van Der Lely A. J. , Lamberts S. W. J. 
Published: November 2003

OBJECTIVERecombinant human growth hormone is being used increasingly in the treatment of GH deficiency in adults. In addition to erythropoietin, insulin‐like growth factor‐I (IGF‐I) has been demonstrated to stimulate hematopoiesis in animals, especially rodents. We have determined the effect of growth hormone (GH) administration on haematopoiesis.PATIENTS AND DESIGNSeventeen patients (10 males and 7 females; mean age 47 ± 2 years; range 30–59) with biochemically proven adult‐onset GH deficiency (GHD) were treated with human recombinant growth hormone (rhGH) as replacement therapy for more than 96 weeks in a dosage of 12.5 μg/kg/day (initial dosage during the first 4 weeks 6.25 μg/kg/day). The diagnosis of GHD had been confirmed using a standard arginine‐infusion test (0.5 g/kg body weight). Blood samples were collected for safety and efficacy parameters before and during the GH treatment period.MEASUREMENTSRoutine methods were used for the haematological and biochemical measurements. IGF‐I concentrations were measured, using a commercial RIA kit.RESULTSFrom week 36 and onwards, we observed a significant increase in individual haemoglobin (Hb) concentrations, especially in the male patients. Mean Hb in the male patients before treatment amounted to 9.1 ± 0.2 mmol/l (range 8.1–10.5) and increased by 0.93 ± 0.2 mmol/l (P < 0.05) after 120 weeks of rhGH replacement therapy. The mean Hb concentration in female patients before treatment was 8.1 ± 0.1 mmol/l and an increase of 0.32 ± 0.1 mmol/l (P < 0.05) was observed after 120 weeks. For all 17 patients the mean increase in Hb after 120 weeks was 0.73 ± 0.2 mmol/l (P < 0.05). IGF‐I concentrations also increased during therapy from 86 ± 9 pg/l to 253 ± 26 pg/l within 24 weeks (P < 0.05). No significant changes in leucocyte or platelet counts were found.CONCLUSIONSLong‐term replacement therapy with rhGH in patients with adult‐onset GHD induces a significant increase in Hb concentrations, while serum leucocyte and platelet counts do not change.
Sporadic phaeochromocytomas are rarely associated with germline mutations in the von Hippel‐Lindau and RET genes
Authors: Bar Merav , Friedman Eitan , Jakobovitz Orit , Leibowitz Gil , Lerer Israela , Abeliovich Dvorah , Gross David J. 
Published: November 2003

OBJECTIVEvon Hippel‐Lindau (VHL) disease and multiple endocrine neoplasia type 2 (MEN2) are autosomal dominant cancer syndromes. In both conditions, phaeochromocytoma is a prominent feature. It has recently been suggested that phaeochromocytoma can be the presenting and sole clinical manifestation of these multi–organ syndromes. The aim of this study was to ascertain the incidence of VHL and MEN2 among patients with sporadic phaeochromocytoma by mutational analysis.PATIENTSTwenty‐seven unrelated patients with biochemically and/or anatomically proven sporadic phaeochromocytoma were evaluated.DESIGN AND MEASUREMENTSConstitutional DNA obtained from the patients was analysed by single stranded conformational analysis (SSCP) for mutations within the VHL gene coding sequence and by denaturing gradient gel electrophoresis (DGGE) for predominant mutations in exons 10, 11 and 16 of the RET proto‐oncogene. The incidence of patients positive for either VHL or RET germline mutations was assessed.RESULTSTwenty‐six of 27 patients had normal SSCP patterns in all three VHL gene exon segments and only one patient, with an atypical clinical presentation, had an aberrant pattern in exon 3 which upon DNA sequencing was shown to harbor a G to A transversion mutation at nucleotide 695. All patients had normal RET exon 10, 11 and 16 DGGE migration patterns.CONCLUSIONMost, if not all, patients with typical unilateral sporadic phaeochromocytoma do not have von Hippel‐Lindau disease or MEN2. Thus, clinical and/or molecular investigation for von Hippel‐Lindau disease and MEN2 in this patient population does not appear to be indicated.