bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gonadotrophin pulsatility in girls with the Turner syndrome: modulation by exogenous sex steroids
Authors: Nathwani N. C. , Hindmarsh P. C. , Massarano A. A. , Brook C. G. D. 
Published: March 2003

OBJECTIVESThe endocrine manisfestation of puberty, nocturnal pulsatile secretion of gonadotrophins precedes the physical manifestations by 2 years. Whether gonadal steroids and inhibin have a role to play in the regulation of pulsatile gonadotrophin release is unclear. The agonadal model, girls with Turner's syndrome (TS), has been used to determine the role of the hypothalamic pulse generator in the ontogeny of gonadotrophin secretion in man. We evaluated the ontogeny of gonadotrophin secretion in TS girls with respect to amplitude and frequency and compared these results to those obtained in a group of normal girls. The effects of treatment with ethinyloestradiol (EE2) or oxandrolone (OX) on parameters of gonadotrophin secretion were also evaluated.PATIENTSWe studied 32 girls with TS, aged 4.3–12.4 years. All were prepubertal at the start of the study and longterm follow up revealed that none entered spontaneous puberty. The pulse amplitude and frequency was evaluated and compared to the results obtained in 23 normal girls, aged 4.9–12.8 years who acted as controls.MEASUREMENTSSamples were taken at 20 minute intervals for 24 h for the measurement of serum concentrations of luteinising (LH) and follicle stimulating (FSH) hormones. The girls were than randomized to receive EE2 or OX and were then re‐admitted 6 months into the course of the treatment for a repeat 24 h serum profile of LH and FSH levels.RESULTSThe girls with TS showed a clearly defined dominant pulse periodicity of 180 min and that in the normal cohort was 160–220 min. The girls with TS had an increased oscillatory activity between 120 and 260 min compared to the normal. Mean 24 h serum gonadotrophin concentration in TS girls was always higher than in the normal cohort. The inflection points of the fitted polynominal regression equation relating sex hormone concentration with age was similar for the two groups. EE2 lead to a significant change in pulse periodicity in TS girls but OX had no significant effect on the pulse periodicity.CONCLUSIONThese results demonstrate that girls with Turner syndrome have gonadotrophin pulse periodicity in the prepubertal years similar to those of normal girls. The oscillatory activity was much greater in girls with Turner syndrome at all ages in the prepubertal years, suggesting a role for the ovary in modulating gonadotrophin secretion in the prepubertal years. Our data confirm that in girls with Turner syndrome the normal pattern of gonadotrophin secretion evolving with time is preserved.
Age‐dependent decline in cortisol levels and clinical manifestations in patients with ACTH‐independent Cushing's syndrome
Authors: Katayama  , Nomura  , Ujihara  , Obara  , Demura  
Published: March 2003

OBJECTIVEAdrenocortical cells change with age in both subcellular morphology and level of steroidogenesis. This study evaluates the influence of aging on hypercortisolism and clinical manifestations in patients with ACTH‐independent Cushing's syndrome due to a cortisol‐secreting adrenal adenoma (CS).DESIGNRestrospective study.PATIENTSThirty‐six (33 females and 3 males) with CS. 31 healthy controls were age‐ and sex‐matched to CS patients.MEASUREMENTPatient age at diagnosis was compared to the degree of hypercortisolism and clinical manifestations. The degree of hypercortisolism was estimated using serum cortisol levels and urinary free cortisol excretion. Positive clinical manifestations were quantified using 12 symptoms and signs which resulted in a clinical score for each patient. Endogenous creatinine clearance, estimated disease duration and gender were analysed as possible factors affecting adenoma‐secreated cortisol.RESULTSPatient age correlated negatively with serum cortisol level (r = −0.417, P = 0.0107, n = 36) and urinary excretion of free cortisol (r = −0.613, P = 0.0002, n = 31). Analysis of Spearman's rank correlation showed that the clinical score decreased with age (ρ = −0.631, P = 0.0004, n = 33). Oedema, weakness/myopathy, hirsutism, striae and psychological changes were infrequent symptoms in the elderly. Using stepwise multiple regression analysis, we estimated the clinical score (Y) by factors of serum cortisol levels (X1:nmol/l), age (X2: years of age) and gender (X3: gender; female = 1, male = 0), i.e. Y = 4.771 + 0.004 X1− 0.064 X2+ 2.548 X3 (r = 0.743, P < 0.0001, n = 33). Results suggested that aging both suppressed cortisol secretion and repressed manifestations directly as an independent factor, although its direct effect may be weak.CONCLUSIONSOur findings indicated the importance of age as a factor modulating hormonal levels and possible clinical manifestations in patients with cortisol‐secreting adenomas.
The IGF‐I/IGFBP system in congenital partial lipodystrophy
Authors: Janssen J. A. M. J. L. , Hoogerbrugge N. , Van Neck J. W. , Uitterlinden P. , Lamberts S. W. J. 
Published: March 2003

BACKGROUND AND OBJECTIVESInsulin and IGF‐I interact at many levels. Little is known about the insulin‐like growth factor‐I/insulin‐like growth factor binding proteins (IGF‐I/IGFBP) system in congenital partial lipodystrophy, a syndrome characterized by insulin resistance, hyperinsulinaemia and absence of truncal and limb fat. Some cases have acromegaloid features with thick skin and large hands and feet in association with normal levels of circulating growth hormone.METHODSIn four females known with congenital partial lipodystrophy, hyperinsulinaemia with acromegaloid features, the number and affinity of the IGF‐I receptors on peripheral blood mononuclear cells (PBMCs), and the concentration of circulating insulin, total and free IGF‐I, IGFBP‐1 and IGFBP‐3 levels were measured in the fasting and the fed state. Cultures of PBMCs of the patients with lipodystrophy were also used to study the effect of IGF‐I stimulation on thymidine uptake in vitro.MEASUREMENTSIn the subjects with lipodystrophy the affinity and the number of the IGF‐I receptors on peripheral mononuclear cells (PBMCs) and erythrocytes did not differ significantly from controls in the fasting state. Insulin levels were significantly higher in subjects with lipodystrophy both in the fasting as well in the fed state. Total IGF‐I, free IGF‐I and IGFBP‐3 levels did not differ but serum IGFBP‐1 levels were lower in lipodystrophy subjects than in healthy controls. The free IGF‐I/IGFBP‐1 ratio was increased in lipodystrophy subjects both in the fasting and the fed states. The effects of IGF‐I stimulation on thymidine uptake by PBMCs of lipodystrophy subjects in the absence of IGFBP‐1 were not different from healthy controls cultures in vitro. When a combination of IGFBP‐1 (in a concentration comparable to the fasting serum IGFBP‐1 levels in lipodystrophy patients found in our study) and IGF‐I was added to PBMC cultures from lipodystrophy patients no decrease in thymidine uptake by PBMCs was found.CONCLUSIONSIn the four subjects with lipodystrophy hyperinsulinaemia, lowered free IGF‐I and IGFBP‐1 levels, but increased free IGF‐I/IGBP‐1 ratios were observed. Low IGFBP‐1 concentrations in culture media did not reduce the stimulating IGF‐I effect on thymidine uptake by PBMCs from lipodystrophy patients. Our data suggest that the observed increased IGF‐I/IGFBP‐1 ratio in lipodystrophy patients contributes to an unopposed biological effect of IGF‐I on IGF‐I receptors, thereby inducing the development of acromegaloid features, acanthosis nigricans and polycystic ovaries in some patients with congenital partial lipodystrophy.
The relationship between the growth hormone and insulin‐like growth factor axis in long‐term survivors of childhood brain tumours
Authors: Achermann John C. , Hindmarsh Peter C. , D. Brook Charles G. 
Published: March 2003

OBJECTIVEWe compared IGF‐1 and IGFBP3 concentrations in a group of adults treated for brain tumours in childhood with those of matched controls, and investigated the relationship between the GH secretory pattern and IGF‐1/IGFBP3 concentrations in the entire group.DESIGNWe performed 24 h serum GH profiles using 20 minute sampling and measured corresponding fasting concentrations of IGF‐1 and IGFBP3.PATIENTSFourteen adult male long‐term survivors of childhood brain tumours were studied. All had received high dose cranial irradiation ( 30Gy; median 12.8 (range 5.8–14.5) years previously). Nine healthy male volunteers acted as controls.MEASUREMENTSIGF‐1 and IGFBP3 concentrations were measured at 06.00 hours. Peak and trough GH activity within the GH profile was analysed by a distribution method which determined the concentration at or below which the serum GH concentration in the profile spent 95% (peak) and 5% (trough) of the total time.RESULTSSerum IGF‐1 levels were significantly lower in the irradiated group (Irradiated: 200 μg/l vs Control: 265 μg/l; P = 0.001) but the difference in serum IGFBP3 (Irradiated: 2.3 mg/l vs Controls: 2.77 mg/l; P = 0.03) was less marked. Peak GH activity was lower in the irradiated subjects (2.59 mU/l vs 9.04 mU/l; P = 0.0004) and correlated strongly with IGF‐1 (r = 0.62; P = 0.002) but less so with IGFBP3 (r = 0.35; P = 0.09). This was strengthened when the range of activity within the profle (peak − trough) was considered. Trough GH activity had a nonsignificant negative correlation with IGF‐1 and IGFBP3 levels.CONCLUSIONThe difference in serum IGF‐1 concentrations between irradiated subjects and controls was greater than the difference in serum IGFBP3. Peak GH activity and the range of activity within the profile correlated strongly with IGF‐1 concentrations but less so with IGFBP3.
The effects of oestrogen exposure on bone mass in male to female transsexuals
Authors: Reutrakul S. , Ongphiphadhanakul B. , Piaseu N. , Krittiyawong S. , Chanprasertyothin S. , Bunnag P. , Rajatanavin R. 
Published: March 2003

OBJECTIVEThe importance of oestrogen on bone mineral density (BMD) in males was suggested by reports of patients with oestrogen resistance and aromatase deficiency who demonstrated osteoporosis and epiphyseal plate maturation defect despite high testosterone levels. In the present study, we examined the effects of oestrogen exposure on BMD in transsexual men.DESIGNCross‐sectional study of BMD in male to female transsexuals.PATIENTSSubjects consisted of two groups of transsexual male dancers aged 16–34 years who did not receive transsexual operations (n = 28). Group 1 (n = 11) and group 2 (n = 17) had used oestrogen for 2 years or less and more than 2 years, respectively. Twenty‐four healthy adult males served as controls.RESULTSsigns of feminization were presented in both group 1 and group 2, with Tanner's stage II–III breast development. BMD at various sites were correlated only to body weight and not to smoking or milk consumption. After controlling for body weight, it was found that group 2 had significantly higher BMD at L2–4 than controls (1.22 ± 0.03 vs. 1.14 ± 0.03 g/cm2, P < 0.05) and group 1 (1.22 ± 0.03 vs. 1.08 ± 0.04 g/cm2, P < 0.05). BMD at femoral neck was also higher in group 2 compared to controls (1.10 ± 0.03 vs. 1.01 ± 0.03 g/cm2, P < 0.05) and group 1 (1.10 ± 0.03 vs. 0.95 ± 0.04 g/cm2, P < 0.05). Group 1 subjects had lower BMD compared to controls at femoral trochanter (0.70 ± 0.04 vs. 0.83 ± 0.03 g/cm2, P < 0.05) and total femur (0.96 ± 0.05 vs. 1.07 ± 0.03 g/cm2, P < 0.05).CONCLUSIONSLong‐term oestrogen exposure transsexual men result in an increase in bone mineral density despite signs of feminization. This suggests that oestrogen has positive effects on bone density in males. The finding of the trend towards reduced bone density in group 1 remains unexplained.
Addison's disease in Africa—a teaching hospital experience
Authors: Soule Steven 
Published: March 2003

OBJECTIVEAddison's disease may present with diverse and non‐specific clinical and biochemical features. Contentious issues include the appropriate criteria for the interpretation of the ACTH stimulation test and the necessary extent of investigation to identify a specific aetiology for the hypoadrenalism. The experience of Addison's disease at a South African teaching hospital was reviewed to (1) record the aetiology and spectrum of presentation, (2) examine the performance of the ACTH stimulation test and (3) determine the utility of adrenal CT scan and biopsy.METHODSRetrospective study of patients admitted to a South African teaching hospital from 1980 to 1997 with a diagnosis of acute Addison's disease.PATIENTS AND MEASUREMENTSFifty patients presenting with acute Addison's disease were identified by a search of hospital records. Pretreatment biochemical and haematological parameters were recorded. The cortisol response at 20 and 60 min to an intravenous injection of 250 μg synacthen (Cortrosyn®) was analysed. In a subgroup of affected subjects, the bone mineral density (BMD) in the lumbar spine and femoral neck was measured during long‐term follow‐up.RESULTSPresenting features included hyperpigmentation (86%), weight loss (67%), abdominal pain (20%) and diarrhoea (16%). Thirty‐nine patients (78%) were hyponatraemic, while 26 (53%) were hyperkalaemic. Nine patients (18%) were hypoglycaemic and 21% had hypercalcaemia. The mean basal cortisol was 148 nmol/l (range 10–487) and 16 patients (40%) had a normal basal cortisol. The mean cortisol 20 min after ACTH stimulation was 172 nmol/l (range 19–588). There was no significant increase in serum cortisol following ACTH stimulation (P > 0.05). Adrenal CT scans were performed in only 24 patients (48%) and were normal in 10, while abnormalities were detected in 14 patients (bilateral enlargement in 11, calcification in two and atrophic adrenals in one). Eight patients had a DEXA scan performed during follow‐up—four were osteopaenic in the lumbar spine and five at the femoral neck. The probable aetiology of Addison's was idiopathic in 42%, related to active TB in 18%, old TB in 16%, autoimmune in 12% and malignancy with metastases in 6%—single cases were due to sarcoid, iron overload and adrenoleukodystrophy. Adrenal biopsy was performed in two patients and was diagnostic of malignancy in both cases. The mortality within the first month after hospitalization was 12%.CONCLUSIONSIn our experience, Addison's disease is frequently idiopathic, presents with protean manifestations and should be considered in patients with unexplained hyperpigmentation or gastrointestinal complaints, particularly when associated with hyponatraemia and hyperkalaemia. A normal basal cortisol does not exclude the diagnosis which requires ACTH stimulation testing.
Insulin regulation of leptin synthesis and secretion in humans: the model of myotonic dystrophy
Authors: Gómez José Manuel , Molina Ana , Fernández‐Castañer Miquel , Casamitjana Roser , Martínez‐Matos Juan Antonio , Soler Juan 
Published: March 2003

OBJECTIVEMyotonic dystrophy (MyD) is a systemic disorder in which insulin resistance is well recognized. In the present study we have characterized plasma leptin levels in patients with MyD and in age, sex and body mass index (BMI) matched controls and assessed the influence of leptin on the clinical manifestations of MyD.DESIGN AND PATIENTSBody composition, plasma leptin, fasting and post‐oral glucose tolerance test insulin, IGF‐I and IGFBP3 were studied in 34 MyD patients and 33 controls.MEASUREMENTSBody composition was measured using a bioelectrical impedance analyzer, and circulating levels of insulin, leptin, IGF‐I, IGFBP3 were measured by IRMA or RIA. Insulin sensitivity was modelled according to a homeostasis model assessment (HOMA) computer‐solved model.RESULTSPercentage body fat was higher in patients than in controls (25.6 ± 2.28% vs 18.8 ± 1.53%, P = 0.013). Insulin levels, both fasting and after oral glucose were higher in patients than in controls, and insulin sensitivity was lower in patients than in controls. Serum leptin was higher in patients than in controls (20.98 ± 3.11 μg/l vs 10.4 ± 1.31 μg/l, P = 0.004), and higher in women than in men, both in patients and in controls. In patients, leptin levels were correlated with age, BMI, fasting insulin, insulin area under curve and lower insulin sensitivity, whereas leptin levels were not correlated with body fat or other parameters of body composition. In controls, leptin levels were correlated with BMI and body fat. The results were evaluated using logistic regression models for each of the 2 populations. In the model of MyD, insulin resistance and age correctly identified higher leptin levels in relation to controls out of 87.88% of patients, and in the model of controls male sex with a negative correlation and BMI correctly identified their leptin levels out of 84.33% cases.CONCLUSIONSThese findings show that MyD provides a different model of leptin regulation in humans, and suggest that in MyD patients there are correlations between leptin and insulin resistance and age, irrespective of body fat. In contrast, leptin levels in controls, correlate with sex and BMI. The data on leptin in this population of patients can not be related aetiologically to the muscle disease itself.
Constitutional delay in growth and puberty (CDGP) is associated with hypoleptinaemia
Authors: Gill Matthew S. , Hall Catherine M. , Tillmann Vallo , Clayton Peter E. 
Published: March 2003

OBJECTIVESerum leptin concentrations are higher in early adolescence compared with childhood and may play a facilitatory role in pubertal development. Constitutional delay in growth and puberty (CDGP) is a disorder of the tempo of physical maturation and may be associated with relative hypoleptinaemia. We have therefore compared serum leptin concentrations in normal boys with those in boys exhibiting constitutional delay of growth, controlling for pubertal status, age and body mass index (BMI).PATIENTS23 boys with constitutional delay in growth (n = 17, prepubertal) and puberty (n = 6, early pubertal) and 88 normal boys (n = 64 prepubertal, n = 24 Tanner stage 2).MEASUREMENTSSerum leptin was measured in a single, non‐fasted morning serum sample by radioimmunoassay. Using the data from normal boys, leptin standard deviation scores (sds) were calculated, to account for the independent influences of age and body mass index (BMI) sds. Both chronological age and bone age were used in the calculation of leptin sds in those with delay.RESULTSBMIsds was significantly lower in prepubertal delays compared with controls but was not different in pubertal subjects. Leptin concentrations were higher in early puberty compared with prepuberty (P < 0.001) in normal boys but were not significantly elevated in pubertal boys with delay compared with prepubertal delays. Although leptin sds, for both chronological age and bone age, was similar in prepubertal controls and delays, it was significantly lower in the pubertal delay group (P < 0.05). In controls leptin sds did not correlate with age. However, in delays leptin sds was negatively correlated with both chronological age (r = − 0.43, P < 0.05) and bone age (r = − 0.68, P < 0.01), indicating that in the older delays leptin levels were lower than expected given their age and BMIsds.CONCLUSIONSThese data indicate that significantly higher leptin levels in Tanner stage 2 compared with prepuberty are not a prerequisite for progression into puberty. However, the absence of elevated leptin concentrations may be associated with delayed puberty in boys.
Effects of administration of 17β‐oestradiol on serum leptin levels in healthy postmenopausal women
Authors: Elbers Jolanda M. H. , De Roo Gerdien W. de Valk‐. , Popp‐Snijders Corrie , Nicolaas‐Merkus Ans , Westerveen Edo , Joenje Bas W. , Netelenbos J. Coen 
Published: March 2003

OBJECTIVEWomen have higher leptin levels than men at a certain degree of adiposity. The role of oestrogens in the regulation of serum leptin levels remains inconclusive. The aim of the present study was to investigate the effect of unopposed oestrogen replacement therapy, during two months, on serum leptin levels in postmenopausal women.DESIGNA double‐blind, placebo‐controlled, randomized study.SUBJECTSTwenty‐five healthy postmenopausal women were studied (mean (± SD) age: 52.9 ± 2.7 years, range of age: 48.7–57.4 years; mean body mass index (BMI): 26.4 ± 4.2 kg/m2, range of BMI: 21.0–39.0 kg/m2). Twelve of these women were treated with 2 mg 17β‐oestradiol daily, and 13 postmenopausal women received placebo.MEASUREMENTSBefore and at the end of a 2‐month study period, anthropometric and bio‐electrical impedance measurements were performed, and fasting blood samples were taken, to determine serum levels of sex hormones and leptin.RESULTSDuring the 2‐month study period, body weight had increased significantly in the placebo group compared with the treatment group, but no significant changes were observed in percentage of body fat or the amount of body fat in kg between the groups. Following administration of 17β‐estradiol, the median leptin level increased from 17.6 μg/l to 24.1 μg/l after 2 months (P = 0.008 compared with baseline). This increase was significantly different from the placebo group (P = 0.019), which showed no change in circulating leptin levels.CONCLUSIONThis study demonstrates that unopposed oestrogen replacement therapy during 2 months in postmenopausal women slightly, but significantly, increases total serum leptin levels. This observation suggests a role for oestrogens in the regulation of leptin.
Mutations in the type II 3β‐hydroxysteroid dehydrogenase (HSD3B2) gene can cause premature pubarche in girls
Authors: Marui  , Castro  , Latronico  , Elias  , Arnhold  , Moreira  , Mendonca  
Published: March 2003

OBJECTIVEMost previous studies have failed to demonstrate any mutations in the type II 3β hydroxysteroid dehydrogenase (HSD3B2) gene in patients satisfying the hormonal criteria of nonclassic 3β‐hydroxysteroid dehydrogenase deficiency, suggesting that a mutant 3β‐hydroxysteroid dehydrogenase protein is not the cause of this disorder. We screened the HSD3B2 gene for mutations in girls with premature pubarche and a hormonal diagnosis of 3β‐hydroxysteroid dehydrogenase deficiency.DESIGNFrom 30 girls with premature pubarche, we selected 9 whose ACTH‐stimulated 17‐hydroxypregnenolone levels were elevated (≥6 SD) and screened the HSD3B2 gene for mutations.MEASUREMENTSAll patients were submitted to a standard ACTH stimulation test. Serum steroids were measured and compared to the mean level of pubertal stage matched control subjects. The four exons and exon‐intron boundaries of the HSD3B2 gene were amplified by polymerase chain reaction and screened for mutations by denaturing gradient gel electrophoresis. The fragments with abnormal migration on denaturing gradient gel electrophoresis were directly sequenced.RESULTSA homozygous T259M mutation was identified in one girl and a new compound heterozygous G129R/P222H mutation was identified in two sisters. The highest ACTH‐stimulated 17‐hydroxypregnenolone levels, 147, 339 and 351 nmol/l, were found in those patients with mutations in the HSD3B2 gene. In the patients without mutations, ACTH‐stimulated 17‐hydroxypregnenolone ranged from 48 to 111 nmol/l. ACTH‐stimulated dehydroepiandrosterone levels had an overlap among the girls with and without mutations and the normal controls.CONCLUSIONSPremature pubarche can be caused by mutations in the type II 3β hydroxysteroid dehydrogenase gene.