bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual dimorphism in 11 β hydroxysteroid dehydrogenase activity and its relation to fat distribution and insulin sensitivity; a study in hypopituitary subjects
Authors: Weaver Jolanta U , Taylor Norman F , Monson John P , Wood Peter J , Kelly William F 
Published: March 2003

OBJECTIVESexual dimorphism of 11 β hydroxysteroid dehydrogenase activity (11 β HSD) as measured by the urinary 11‐OH/11‐oxo cortisol metabolite ratio has been documented in healthy subjects. Since body composition, fat distribution and insulin sensitivity vary between the sexes we have investigated whether these factors may account for the observed difference. Studies were performed in ACTH deficient hypopituitary subjects to eliminate the effect of feedback modulation of cortisol secretion.DESIGN AND PATIENTS44 hypopituitary patients, (m:f, 32:12), median age 51 years, median weight 86 kg, on hydrocortisone and other replacement therapy as appropriate were studied.MEASUREMENTUrine 11‐OH/11‐ oxo cortisol metabolites and serum and urine cortisone (E) and cortisol (F) were measured in relation to total cortisol metabolites and cortisol binding globulin; fat distribution was assessed by Dual Energy X‐ray absorptiometry (DXA), and insulin sensitivity by homeostatic model of assessment.RESULTSCortisol bioavailability (total urine cortisol metabolites, urine free cortisol and cortisol binding globulin) was similar in both sexes. The 11‐OH/11‐oxo ratio was lower in females than males (median; 0.99 vs 1.3, P < 0.03) while thyroid status was similar. Females had higher percentage fat (median 47.7 vs 34.9, P < 0.01); total fat (median 39.5 vs 34.9 kg, P < 0.01), android fat (median 9.1 vs 6.6 kg, P < 0.01); gynoid fat (median; 9.9 vs 6.8 kg, P < 0.05) and lower insulin sensitivity (median 15.3 vs 30.6, P < 0.01). In all subjects, the 11‐OH/11‐ oxo ratio was inversely related to body weight (P < 0.01), % fat (P < 0.05), total fat (P < 0.01), android fat (P < 0.01), gynoid fat, (P < 0.01) and directly correlated to insulin sensitivity, P < 0.01. Stepwise regression analysis showed gynoid fat to be the most important factor determining the 11‐OH/11‐oxo ratio. In 24 subjects (f : m, 8 :16) on exogenous sex steroid therapy insulin sensitivity was similar but the sexual dimorphism of the 11‐OH/11‐oxo ratio remained unchanged (median; 1.0 vs 1.7, P < 0.05). The urine and serum F and E and their ratio (F/E) were similar in these groups.CONCLUSIONThese data confirm the presence of sexual dimorphism in 11 β‐hydroxysteroid dehydrogenase activity in hypopituitary patients as described in normal individuals. This is the first in vivo evidence that this dimorphism is related to body composition. Our findings suggest that sexual dimorphism may be determined by the activity of type 1 and not type 2 11 β‐hydroxysteroid dehydrogenase.
Neurohypophysial hormone and melatonin secretion over the natural and suppressed menstrual cycle in premenopausal women
Authors: Kostoglou‐Athanassiou Ifigenia , Athanassiou Panagiotis , Treacher David F , Wheeler Michael J , Forsling Mary L 
Published: March 2003

OBJECTIVEVasopressin, oxytocin and melatonin have been reported to be influenced by ovarian steroids. The neurohypophysial hormones have also been shown to display a diurnal pattern of secretion in men. We therefore studied the diurnal pattern of neurohypophysial hormone and melatonin secretion in premenopausal women and in women on oral contraceptives.DESIGNHealthy normally cycling premenopausal women were studied over 24 hours during the midfollicular and midluteal phases of the menstrual cycle. Healthy premenopausal women on oral contraceptives were studied over 24 hours at similar times.SUBJECTSEight healthy normally cycling women and 7 healthy premenopausal women on oral contraceptives.MEASUREMENTSPlasma vasopressin, oxytocin and melatonin were measured by radioimmunoassay.RESULTSVasopressin concentrations and its nocturnal peak were highest in the follicular phase of the natural menstrual cycle and attenuated in the women on oral contraceptives. Oxytocin concentrations did not vary between the two phases of the menstrual cycle, but increased on oestrogen administration. Overall melatonin secretion was augmented in the women on oral contraceptives.CONCLUSIONSVasopressin release and its nocturnal peak were greatest in the follicular phase of the menstrual cycle, while melatonin secretion was augmented in the women on oral contraception.
The impact of obesity on cardiovascular risk factors in Turner's syndrome
Authors: Elsheikh Mohgah , Conway Gerard S. 
Published: March 2003

OBJECTIVETo evaluate risk factors for coronary artery disease in women with Turner's syndrome which may contribute to the increased incidence of premature cardiovascular death noted in this disorder.DESIGNComparison of clinical and biochemical parameters in women with Turner's syndrome with those in women with normal karyotype.PATIENTSNinety‐one women with Turner's syndrome attending a dedicated adult Turner's syndrome clinic and 22 control subjects were studied.MEASUREMENTSRecumbent blood pressure, body mass index (BMI), fasting total cholesterol, triglycerides and high density lipoproteins (HDL) were measured in both study groups.RESULTSWomen with Turner's syndrome were more obese compared with women with a normal karyotype. They were more likely to be hypertensive and the obese patients had higher serum triglyceride concentrations. Hypertension was independent of obesity and may be under‐recognized because of failure to compare with age‐matched normal ranges. Lipoprotein changes were accounted for by the obesity.CONCLUSIONSWomen with Turner's syndrome may be at increased risk of developing coronary artery disease as a result of the higher frequency of hypertension and obesity. Routine screening of this population for risk factors for ischaemic heart disease is recommended.
Inhibin B levels in azoospermic subjects with cytologically characterized testicular pathology
Authors: Foresta Carlo , Bettella Andrea , Petraglia Felice , Pistorello Matteo , Luisi Stefano , Rossato Marco 
Published: March 2003

BACKGROUND AND OBJECTIVEInhibin B, a heterodimeric glycoprotein of gonadal origin, is the most important circulating form of inhibin in human males and an inverse relationship between inhibin B and FSH plasma levels was been recently observed. Azoospermia represents the end‐point of different kinds of testicular damage, ranging from a normal spermatogenic pattern (obstructive forms) to the complete absence of germ cells (Sertoli Cell Only Syndrome, SCOS). Furthermore, azoospermia may be related to maturational disturbances at different levels (spermatogonial, spermatocytic, spermatidic). To better define the relationship between testicular damage and inhibin levels and to evaluate the diagnostic value of this hormone in the management of subjects with azoospermia, we performed specific inhibin B assays in a group of azoospermic subjects affected by different kinds of testicular pathology.PATIENTSEighty‐nine azoospermic men were studied by testicular ultrasound examination, fine needle aspiration of the testes and hormonal parameters (FSH, LH and testosterone, inhibin B). Thirty normozoospermic subjects were considered as controls for seminal and hormonal parameters.DESIGN AND RESULTSOn the basis of cytological analysis five different testicular appearences were identified in azoospermic patients: (i) Sertoli cell only syndrome (SCOS); (ii) Severe hypospermatogenesis; (iii) Spermatogonial and/or spermatocytic arrest; (iv) Spermatidic arrest; (v) Normal germ line (obstructive forms). No difference in LH and testosterone levels was found among the different groups. A significant negative correlation was present between inhibin B and FSH both in azoospermic men (r = − 0.503, P < 0.0001) and normozoospermic controls (r =−0.361, P < 0.05). Groups characterized by obstructive azoospermia and spermatidic arrest showed inhibin B concentrations similar to normozoospermic subjects (130.7 ± 73.5, 160.3 ± 35.1 and 148.5 ± 46.8 ng/l, respectively), while groups characterized by SCOS, severe hypospermatogenesis and spermatogonial and/or spermatocytic arrest showed mean inhibin B concentrations significantly lower than controls (56.5 ± 56.0, 57.9 ± 31.2; 48.9 ± 16.7 ng/l, respectively). In the group of SCOS, 8 out of 42 subjects (19.0%) showed inhibin B concentrations within the normal range despite high FSH levels.CONCLUSIONSThis study demonstrated that, in humans, spermatids play an important role in the mechanism regulating inhibin B secretion by Sertoli cells. The significance of this hormone as a diagnostic parameter in azoospermic patients does not seem to be specific because it does not permit discrimination between obstructive forms or spermatidic arrest. Furthermore, despite an evident clinical, cytological and hormonal pattern for SCOS, inhibin B levels are normal in some of these patients. The significance of this latter result remains to be elucidated.
Diagnosis and treatment of the solitary thyroid nodule. Results of a European survey
Authors: Bennedbæk Finn Noe , Perrild Hans , Hegedüs Laszlo 
Published: March 2003

BACKGROUND AND OBJECTIVEThe optimum diagnostic and therapeutic strategy for the euthyroid patient with a solitary thyroid nodule is still a matter of debate. The aim was to assess the attitudes towards management of such patients in clinical centres throughout Europe by means of a questionnaire.DESIGNThe questionnaire was circulated to all clinical members of the European Thyroid Association (ETA). A case report was followed by diagnostic investigations and choice of therapy in the index case (a 42‐year old woman with a solitary 2 × 3 cm thyroid nodule and no clinical suspicion of malignancy). Eleven variations of the basic case report were proposed in order to evaluate how each alteration would affect management.MATERIAL151 members replied to the letter and 110 individuals from 20 countries completed the questionnaire (corresponding to approximately two‐thirds of the clinical members of the ETA). They represented clinicians who had diagnosed and treated more than 50 (76%) or less than 50 (24%) patients with nodular thyroid disease within the previous 6 months.RESULTSBased on the index case, basal serum TSH was the routine choice of 99% and serum T4 and/or free T4 were included by 70% of the respondents. Almost 50% included determination of serum thyroid autoantibodies (TPOab: 47%, Tgab:26%) and 43% measured serum calcitonin. Thyroid scintigraphy was used by 66% (99mTc: 86%, 123I: 10%, 131I: 4%), ultrasonography (US) by 80% (size: 75%, grey scale: 57%, Doppler: 33%). Scintigraphy in addition to US was used by 58%. Fine‐needle aspiration biopsy (FNAB) was routinely used by 99% of the respondents, and performed under US‐guidance by 42%. Based on the individually chosen diagnostic tests indicating a benign solitary thyroid nodule, a non‐surgical strategy was advocated by 77%. Despite controversies on L‐T4 treatment this treatment was supported by more than 40% of the clinicians. Surgery was advocated by 23% and the preferred technique was hemithyroidectomy (70%). Clinical factors raising suspicion of thyroid malignancy (e.g. family history of thyroid cancer, history of external radiation, rapid nodule growth and a large nodule of 5 cm) lead the majority (70–91%; P < 0.000001) to disregard FNAB results and to choose a surgical strategy.CONCLUSIONSThe favoured diagnostic strategy in the workup of patients with a solitary thyroid nodule include determinations of serum TSH combined with serum T4 and/or free T4 followed by FNAB and US together with scintigraphy. A nonsurgical strategy was favoured by the majority supporting the use of L‐T4 as the first choice. In case of clinical factors raising the likelihood of malignancy, the majority recommended diagnostic thyroidectomy despite FNAB suggesting a benign condition.
Effect of acute high dose dobutamine administration on serum thyrotrophin (TSH)
Authors: Lee Edwin , Chen Peijun , Rao Harsha , Lee Jenifer , Burmeister Lynn A. 
Published: March 2003

OBJECTIVEThe interpretation of thyroid function tests in the setting of severe illness is often complicated by concomitant drug administration which may independently produce changes in thyroid hormone concentrations or even secondary hypothyroidism. Although the effects of dopamine on TSH are well established, the effects of dobutamine, another drug commonly used in the setting of severe illness, on TSH are unknown. The aim of the study was to establish the effect(s) of acute high dose dobutamine on serum TSH concentration.DESIGN AND PATIENTSThirty subjects undergoing dobutamine stress echocardiogram were compared to twenty controls. Serum TSH was determined between the hours of 0800 and 1000 h at baseline, at maximum dobutamine infusion (20–50 μg/kg/min and 15 minutes after stopping dobutamine.MEASUREMENTSSerum TSH concentration was measured using a third generation chemiluminescent assay.RESULTSTSH concentration decreased with time in both dobutamine and control subjects and there was an additional statistically significant effect of dobutamine treatment to decrease TSH. TSH concentration remained within the normal range in all subjects who started with normal TSH concentration and remained above normal in the three dobutamine‐treated subjects with elevated TSH at baseline. The dobutamine‐associated decrease in TSH was still present 15 minutes after discontinuing dobutamine.CONCLUSIONSThese results indicate that acute high dose dobutamine lowers TSH by an unknown mechanism. Additional study with prolonged dobutamine infusion is needed to establish the steady state level and physiological consequences of dobutamine‐inhibited TSH.
Octreotide‐scintigraphy is a disease‐activity parameter in Graves' ophthalmopathy
Authors: Gerding M. N. , van der Zant F. M. , van Royen E. A. , Koornneef L. , Krenning E. P. , Wiersinga W. M. , Prummel M. F. 
Published: March 2003

OBJECTIVEIt is thought that immunosuppressive treatment of Graves' ophthalmopathy should be restricted to patients with active eye disease, but assessing disease activity is difficult. Octreotide scintigraphy has been claimed to differentiate active from inactive disease. Here we study the intraobserver variability and diagnostic accuracy of the quantitative measurement of orbital octreotide uptake.PATIENTS AND DESIGNTwenty‐two consecutive patients with moderately severe ophthalmopathy were treated with retrobulbar radiotherapy. Pretreatment octreotide scintigraphic data were related to the response at six months after radiotherapy, using Receiving‐Operator‐Characteristic curves.MEASUREMENTSOctreotide uptake was measured at 4 and 24 h after i.v. injection of approximately 3 mCi (= 111 MBq; range 75–150 MBq) 111Indium‐DTPA‐Octreotide with a neuro‐SPECT camera. Counts were measured in fixed regions‐of‐interest in 4 transversal slices of the orbit, the temporal and the occipital area. Measurements were done twice and intraobserver variability was analysed by coefficients of variations (CV). Uptake is expressed as orbital/background ratio. The nature of the temporal uptake was studied by matching an octreoscan with a technetium scan and MRI.RESULTSIntra‐observer variability of measuring octreotide uptake was acceptable, and the coefficient of variation slightly better using the orbital/occipital ratio (11%), than the orbital/temporal ratio (16%). From matching studies it appears that the temporal uptake takes place, in part, in the parotid gland. The orbital/occipital ratio was used to predict the outcome of radiotherapy. Mean (± SD) uptake on the 4 h scan was higher in responders (2.2 ± 0.66) than in nonresponders (1.7 ± 0.39; P = 0.04). From the Receiving‐Operator‐Characteristic curve we determined a cut‐off value of 1.85, which yielded a positive predictive value of 92% and a negative predictive value of 70%.The 24 h scan could not predict a response.CONCLUSIONQuantitative measurement of orbital octreotide uptake is possible. Using the orbital/occipital ratio on the 4 h scan, the octreoscan seems useful in predicting response to subsequent radiotherapy. The 24 h scan seems not to be useful in predicting therapeutic outcome.
Prevalence and significance of thyroid autoantibodies in patients with chronic hepatitis C virus infection: a prospective controlled study
Authors: Huang Miau‐Ju , Tsai Sun‐Lung , Huang Bie‐Yu , Sheen I‐Shyan , Yeh Chau‐Ting , Liaw Yun‐Fan 
Published: March 2003

OBJECTIVETo clarify controversies on the prevalence and clinical significance of thyroid autoimmunity in hepatitis C virus (HCV) infection.DESIGNA prospective controlled and follow‐up study.PATIENTS AND MEASUREMENTSSerum thyroid microsomal antibody (TMA) and thyroid stimulating hormone were assayed and compared in a consecutive, unselected series of 130 patients with chronic HCV infection, 130 sex/age (± 2 years)‐matched patients with chronic hepatitis B virus (HBV) infection and 260 matched normal controls.RESULTSThe prevalence of thyroid autoantibodies in male patients with chronic HCV was < 2%. The prevalence of TMA (< 1 : 400) in female patients with chronic HCV infection was significantly higher than that of HBV controls (22.1 vs. 1.6%; P < 0.001), and higher but not significant compared with normal controls (13.5%). However, the trend of increasing prevalence with age in normal controls was not observed in HCV patients. TMA seropositive female HCV patients were not different from seronegative counterparts in age, duration of infection, HLA haplotype, associated autoantibodies and liver histology but had a significantly higher prevalence of genotype 1b/2b mixed infection (P < 0.01) and anti‐GOR (P < 0.05). Of the 23 HCV patients seropositive for thyroid autoantibodies, seven had Hashimoto's thyroiditis, two had Graves' disease and three had received subtotal thyroidectomy. During follow‐up, four of 15 female patients showed a 14–16‐fold increase in TMA titre and one developed hyperthyroidism. Patients with thyroid autoantibodies did not show a propensity to develop thyroid dysfunction during interferon therapy.CONCLUSIONSThese results suggest a weak association between HCV and thyroid autoimmunity in females. As in the ordinary population with thyroid autoantibodies, they should be evaluated for thyroid status and be followed‐up if thyroid autoimmunity is evident. However, seropositivity of thyroid autoantibodies is not a contraindication to interferon therapy.
Apoptosis in neuroendocrine tumours
Authors: Wang Da‐Gong 
Published: March 2003

Acquired resistance to apoptosis in neuroendocrine tumours (NETs) may promote clonal expansion and enhance the likelihood that subsequent mutations lead to growth or persistence of the neoplastic clone. Recent studies have demonstrated that deregulation of programmed cell death may be a critical component in multistep tumourigenesis of NETs and that the frequent expression of the Bcl‐2 oncoprotein in these tumours may contribute to their pathogenesis. The genetic complementation of simultaneously deregulated Bcl‐2 and c‐Myc may be implicated in the multistep tumourigenesis of human NETs.Furthermore, because the efficacy of cytotoxic chemotherapy relies on its ability to induce programmed cell death, resistance to apoptosis typically correlates with chemoresistance, a phenomenon that is typical in NETs. Consideration of how oncogenes affect rates of cell death, in addition to augmenting growth, has already provided valuable insights into the biology of cancer. Understanding the molecular and cellular features of this process may enable the development and application of more effective and potentially curative treatment strategies in which the induction of programmed cell death is an integral component.
Lipid profile, glucose tolerance and insulin sensitivity after more than four years of growth hormone therapy in non‐growth hormone deficient adolescents
Authors: Bareille Philippe , Azcona Cristina , Matthews David R , Conway Gerard S. , Stanhope Richard 
Published: March 2003

OBJECTIVETo study the effects of long‐term (> 4 years) growth hormone (GH) therapy on insulin sensitivity, glucose tolerance and lipid profile in non‐GH deficient adolescents at completion of their growth.SUBJECTSThirty non‐GH deficient (15 ‘idiopathic’ short stature, 8 intrauterine growth retardation, 7 partial GH deficiency in childhood but normal on retesting) were recruited, median (range) age 16.9 years (15–20.3) prior to ceasing their GH therapy. Their median (range) duration of GH treatment was 7.9 years (4–11). Insulin sensitivity was also recorded in 10 normal controls with a median (range) age of 20.5 years (18.4–22.3).METHODSInsulin sensitivity was assessed by a short insulin tolerance test in 18 patients on GH therapy and controls. It was repeated in 14 patients six months after stopping their GH therapy. A 3‐h standard oral glucose tolerance test (OGTT) was performed in 19 patients on GH therapy, and repeated after 6 months off GH in 10 patients. Fasting lipids were also measured.RESULTSInsulin sensitivity index was significantly lower in the patients on GH therapy than in the controls, (median (range)) 3.7%/min (1.2–5.3) and 5.3%/min (3.8–6.2), respectively. Six months after termination of GH therapy, insulin sensitivity increased significantly from 3.6%/min (1.2–5) to 4.8%/min (2.8–5.6). Fasting plasma insulin decreased significantly off GH therapy from 10.1 to 3.6 mU/l. The area under the insulin curve during the OGTT was also significantly higher on GH therapy. Apart from one patient with impaired glucose tolerance on GH treatment, plasma glucose concentrations remained within the normal range. No lipid abnormalities were recorded.CONCLUSIONSThese data suggest that long‐term GH therapy may cause insulin resistance in non GH deficient adolescents, but usually with neither impaired glucose tolerance nor hyperlipidaemia.