bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating leptin concentrations in polycystic ovary syndrome: relation to anthropometric and metabolic parameters
Authors: Chapman Ian M. , Wittert Gary A. , Norman Robert J. 
Published: November 2003

OBJECTIVE To determine the relation between metabolic and anthropometric parameters and circulating leptin concentrations in women with polycystic ovary syndrome (PCOS).DESIGN AND PATIENTS Correlation of fasting serum leptin concentrations with anthropometric measures and multiple metabolic parameters including insulin and glucose responses to a 2‐hour 75‐g oral glucose tolerance test (OGTT) in 85 women with PCOS (17–36 years, body mass index (BMI) 29.9 ± 0.9 kg/m2, mean ± SD) and 18 control women (25–47 years, BMI 25 ± 1.7 kg/m2). Diagnostic criteria for PCOS: characteristic ovarian morphology on ultrasound plus at least two of (1) elevated serum testosterone; (2) elevated serum androstenedione; and (3) reduced serum SHBG concentrations.MEASUREMENTS Concentrations of androgens, lipids, PRL, gonadotrophins, and leptin were measured in the baseline fasting blood sample from an OGTT. Insulin and glucose were measured throughout OGTT. Serum leptin concentrations were measured by radioimmunoassay.RESULTS Log leptin levels in the PCOS group correlated significantly with BMI (r = 0.85, P < 0.0001) and with 8 other parameters including waist/hip ratio (r = 0.51, P = 0.0005). By stepwise regression analysis, only BMI (P < 0.0001) and plasma high density lipoprotein concentration (P = 0.02) were independently correlated with log leptin levels, both positively. There was no effect of fat distribution, as measured by waist/hip ratio, on leptin concentrations. Comparison of control subjects to a BMI‐matched subgroup of 55 PCOS subjects revealed significantly higher circulating concentrations of LH, testosterone, DHEAS, progesterone and androstenedione, and higher glucose and insulin responses to OGTT in the PCOS group. Leptin levels were not different between the PCOS subgroup and control group (14.8 ± 1.3 vs 12.1 ± 2.3 μg/l, mean ± SE, P = 0.26) and the relation of BMI to leptin levels determined by linear regression analysis also did not differ between the two groups.CONCLUSIONS Our results indicate that circulating leptin concentrations in women with PCOS, a condition characterized by hyperandrogenaemia, increased LH concentrations and insulin resistance, are strongly related to BMI and not independently affected by circulating levels of insulin, gonadotrophins or sex hormones.
Placental 11β‐hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure
Authors: Benediktsson Rafn , Calder Andrew A. , Edwards Christopher R. W. , Seckl Jonathan R. 
Published: November 2003

OBJECTIVE Placental 11β‐hydroxysteroid dehydrogenase (11β‐HSD), which converts active cortisol to inactive cortisone, has been proposed to be the mechanism guarding the fetus from the growth retarding effects of maternal glucocorticoids; however, other placental enzymes have also been implicated. Placental 11β‐HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid metabolism in dually perfused freshly isolated intact human placentas.DESIGN Placentas were obtained from randomly selected normal term deliveries. The maternal circuit was perfused with physiological concentration of cortisol, the fetal effluent collected and steroid metabolites separated and quantified using silica columns (Sep‐pak Plus) and HPLC.RESULTS Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. Cortisone was the only product of cortisol metabolism. Inhibition of 11β‐HSD with glycyrrhetinic acid allowed cortisol to gain direct access to the fetal circulation.CONCLUSION We conclude that human placental 11β‐HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.
Acute administration of hexarelin stimulates GH secretion during day and night in normal men
Authors: Loche Sandro , Colao Annamaria , Cappa Marco , Ferone Diego , Merola Bartolomeo , Faedda Antonella , Imbimbo Bruno P. , Deghenghi Romano , Lombardi Gaetano 
Published: November 2003

OBJECTIVE Hexarelin is a synthetic hexapeptide with potent GH‐releasing activity in both animals and men. The aim of this study was to investigate the effect of a bolus injection of hexarelin given in the morning during wakefulness and during nocturnal sleep in a group of normal adult men.DESIGN AND SUBJECTS Eight normal men, aged 21–33 years, of normal height and within 10% of ideal body weight were studied. All subjects received in random order saline or hexarelin (2 μg/kg) in the morning between 0800 and 0900 h after they had fasted overnight. The same experiments were performed during nocturnal sleep in the same subjects. Saline or hexarelin were injected within 30 minutes after the onset of sleep between 2300 and 2400 h. Sleep was recorded by visual inspection.MEASUREMENTS In all four test sessions blood samples were taken 30, 15 minutes and immediately before the injection of saline or hexarelin and then every 15 minutes for 2 hours. GH was measured by an immunoradiometric assay. All values are expressed as peak GH levels or as area under the curve (AUC) calculated by trapezoidal integration.RESULTS Mean peak GH concentrations after hexarelin during the morning (58.2 ± 4.7 μg/l) (GH μg/l × 2 = mU/l) were not different from those observed during sleep (61.2 ±4.3 μg/l). The rate of disappearance of GH from plasma was slower during sleep (t1/2 =64.9 ±14.8 min) than during morning hours (t1/2 = 24.9 ±1.4 min, P <0.01). Mean AUC responses to hexarelin during sleep (1466 ± 145 μg.min/l) were significantly higher than during morning hours (903 ± 94 μg.min/l, P < 0.001).CONCLUSIONS These results show that GH responsiveness to a growth hormone releasing peptide is preserved during the night. This could be exploited for diagnostic and/or therapeutic purposes.
Serum leptin concentrations in patients with anorexia nervosa, bulimia nervosa and non‐specific eating disorders correlate with the body mass index but are independent of the respective disease
Authors: Ferron Fernando , Considine Robert V. , Peino Roberto , Lado Isabel G. , Dieguez Carlos , Casanueva Felipe F. 
Published: November 2003

OBJECTIVE Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but little else is known about the physiological actions of leptin in humans. The aim of this study was to determine the role of leptin in severe eating disorders, and whether its levels are correlated with the specific disease or exclusively with body weight.TESTS Serum concentrations of human leptin were analysed by specific radioimmunoassay and compared with the individual body mass indexes (BMI). The correlations between serum leptin concentrations and BMI, age and height were analysed.PATIENTS A total of 65 women were studied: 25 patients with anorexia nervosa, 20 women with bulimia nervosa, 6 women with a diagnosis of non‐specific eating disorder, and 14 normal‐weight women who acted as controls. At the time of the study, the patients were non‐cured, under treatment, and at different stages of therapeutic evolution.MEASUREMENTS Plasma leptin levels were measured by specific radioimmunoassay.RESULTS The mean serum leptin in the normal‐ weight women was 10.5 ±1.1 μg/l, compared with 7.6 ±1.1 μg/l in the anorexia nervosa patients (P <0.05). This reduction in leptin levels was paralleled by the differences in BMI (21.4 ±0.4 vs 18.8 ±0.2) P < 0.05. These differences between the controls and anorexia nervosa patients were not observed in patients with bulimia nervosa who had a mean serum leptin level of 9.9 ±1.4 μg/l and BMI of 21.3 ±0.6, neither significantly different from controls. On the contrary, patients with non‐specific eating disorders showed a large reduction in BMI (17.9 ±1.2, P <0.05 vs control), and a parallel reduction in serum leptin levels, 4.5 ±1.0 (P <0.05 vs controls). When individual values of leptin were plotted against BMI a wide range was observed in all groups; in the control subjects from 5.6 to 17.7 μg/l, in anorexia nervosa patients from 2.1 to 28.1 μg/l, in patients with bulimia nervosa between 2.6 and 25.9 μg/l, and in women with non‐specific eating disorder from 2.0 to 8.9. No correlation was observed with the specific disease but in each group a significant correlation was observed only with BMI.CONCLUSIONS Serum leptin levels in three groups of patients affected by severe eating disorders are not related to the specific pathology but are correlated with the individual BMI. The analysis of leptin values may be a useful index of assessing the adipose tissue stores in the clinical setting, but will be of no help for diagnosis nor prognosis of severe eating disorders.
Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine
Authors: Guo Chun‐Yuan , Weetman Anthony P. , Eastell Richard 
Published: November 2003

OBJECTIVE The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover.DESIGN A prospective study over 2 years of postmenopausal women treated with T4 with an age‐ and sex‐matched healthy control group.PATIENTS AND MEASUREMENTS Sixty‐four postmenopausal women, ages 47 to 74 (61 ±9, mean ± SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n =23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n =23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty‐six age‐matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual‐energy X‐ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2.RESULTS The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross‐linked N‐telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = −0.41 P < 0.001, r = −0.29 P =0.01 and r = −0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow‐up (ANOVA, P >0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t‐test, P =0.0021, 0.034, 0.0017, 0.011 and >0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P <0.05).CONCLUSIONS In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.
Effect of mifepristone on folliculogenesis in women treated with recombinant FSH
Authors: Messinis I. E. , Krishnan M. , Kazem R. , Khadilkar S. , Templeton A. A. 
Published: November 2003

OBJECTIVE To study the mechanism through which mifepristone interrupts folliculogenesis.DESIGN Normally ovulating women undergoing donor intrauterine insemination (IUI) treatment were investigated during two menstrual cycles treated with gonadotrophins. In the first cycle (FSH cycle), the women were given 150 IU recombinant FSH (rFSH) s.c. on days 2, 4, 6, 8 and daily thereafter until the administration of hCG. During the second cycle (FSH + mifepristone cycle), the women received rFSH as above plus mifepristone tablets at a dose of 50 mg/day from cycle day 2 until the hCG injection. IUI was performed only in the FSH cycles.PATIENTS Eleven normally ovulating women were studied. The women were used as their own controls during the cycle treated with rFSH only.RESULTS Two women became pregnant during the FSH cycle and, therefore, data for comparison between the two cycles were available in nine women. In both cycles, only one follicle reached the preovulatory stage. However, during treatment with FSH + mifepristone the growth of the dominant follicle was temporarily arrested after day 8 of the cycle and ovulation was postponed by 2 days on average. Serum FSH values increased significantly in both cycles only during the daily administration of rFSH, i.e. towards the end of the experimental period when a normal growth of the follicle was re‐established. On the day of hCG injection, an endogenous LH surge had already started in six of the nine cycles treated with FSH (67%) but in none of the FSH + mifepristone cycles despite the preovulatory oestradiol (E2) levels. Endometrial thickness during the follicular phase and serum E2 and progesterone concentrations during the luteal phase, although in the normal limits, were significantly lower in the FSH + mifepristone than in the FSH cycles.CONCLUSIONS These results suggest that mifepristone arrests follicular development at a stage beyond the recruitment‐selection point by delaying the growth of the dominant follicle. This is probably achieved through an effect of mifepristone on the ovary where it reduces the sensitivity of the selected follicle to FSH. Mifepristone may have a potential application for the inhibition of the LH surge in superovulation induction programmes.
Iodine insufficiency and neonatal hyperthyrotropinaemia in Hong Kong
Authors: Kung Annie W. C. , Lao Terence T. , Low Louis C. K. , Pang Richard W. C. , Robinson J. D. 
Published: November 2003

OBJECTIVES 23% of the neonatal hypothyroidism in Hong Kong is transient. The present study aims to evaluate iodine excretion in healthy pregnant women in Hong Kong and to determine whether iodine insufficiency may occur in the local population to account for the type of neonatal thyroid dysfunction seen in our screening programme.SUBJECTS Pilot screening of urinary iodine excretion was determined in 253 healthy pregnant women between 32 and 36 weeks gestation. Fetal and maternal thyroid function in relation to urinary iodine excretion was evaluated in another 55 pregnant women who had given birth to infants with cord blood TSH ≥ 16 mIU/l (95th percentile of the cord blood TSH screening programme) and the results were compared to a control group of 160 healthy women whose infants had cord blood TSH < 16 mIU/l.RESULTS Using a cut‐off value of 0.79 μmol/l, a level as defined by WHO as iodine deficiency, we found that 35.8% of the pregnant women had urinary iodine concentrations below this cut off value. We demonstrated that the existence of borderline iodine supply affected the maternal and fetal thyroid function as evidenced by (i) a negative correlation between maternal TSH and urinary iodine concentration, (ii) higher cord blood TSH in those infants whose mothers had a low urinary iodine concentration as compared to those in whose mothers it was normal, (iii) women who had given birth to infants with cord blood TSH ≥6 mIU/l had lower urinary iodine concentrations and serum fT4 levels as compared to mothers who had given birth to infants with normal cord TSH levels, and their offspring also had higher cord blood thyroglobulin levels.CONCLUSION Although Hong Kong is not a goitrous area, borderline iodine deficiency exists. Iodization of salt in our community could obviate the necessity for iodine supplements in pregnant women and other at‐risk groups.
Urinary growth hormone following exercise to assess growth hormone production in adults
Authors: Flanagan D. E. H. , Taylor M. C. , Parfitt V. , Mardell R. , Wood P. J. , Leatherdale B. A. 
Published: November 2003

OBJECTIVE The insulin stress test (IST) is the most commonly used test to assess the GH reserve in children and adults. It is a time‐consuming, expensive and potentially dangerous test. We investigated whether measurement of urinary growth hormone excretion following exercise would prove a reliable method to diagnose adult GH deficiency.DESIGN Healthy volunteers underwent a standard IST to confirm normal GH secretion. Using a standardized exercise protocol on a treadmill, the urinary excretion of GH was measured. Three patients confirmed as GH deficient by an IST were exercised using the same exercise protocol and their urinary excretion of GH was measured.PATIENTS Ten healthy volunteers and three patients with hypopituitarism were evaluated.MEASUREMENTS A standard IST was performed on both healthy volunteers and patients, with measurements of plasma GH and plasma cortisol. Urinary growth hormone and urinary GH/creatinine (GH/CR) ratios were measured before and after IST. On a separate visit, healthy volunteers and patients were exercised on the treadmill with measurements of plasma GH and cortisol. Urinary GH and GH/CR ratios were measured before and after exercise.RESULTS There was at least a two‐fold increase in urinary GH and GH/CR ratios following exercise in all healthy adults. By contrast, patients with GH deficiency showed no rise in urinary GH or urinary GH/CR ratios following exercise.CONCLUSIONS Measurements of urinary GH following exercise can distinguish between GH‐deficient adults and healthy volunteers. Urinary GH excretion can be measured over a timed interval following exercise or can be expressed as the GH/CR ratio. This can be measured on a single sample following exercise and can be used to diagnose GH deficiency. The exercise test employed for this study is arduous. We are therefore performing further studies with a less strenuous exercise protocol with a view to designing a ‘patient‐friendly’ exercise test for GH deficiency in adults.
A comparison of different methods for diagnosing acromegaly
Authors: Stoffel‐Wagner B. , Springer W. , Bidlingmaier F. , Klingmüller D. 
Published: November 2003

OBJECTIVEThe present study was designed to assess the diagnostic value of different single measurements in comparison to the classic time‐consuming method, the oral glucose tolerance test (OGTT), in acromegaly.DESIGN, PATIENTS AND MEASUREMENTS IGF‐I, free IGF‐I, 24‐hour‐urinary GH (uGH), serum IGFBP‐3 and 24‐hour‐urinary IGFBP‐3 (uIGFBP‐3) were measured in 12 patients with untreated active acromegaly, in 29 patients who had been treated but were not cured, in 13 patients with cured acromegaly and in 14 healthy control subjects, and compared with the results of the OGTT.RESULTSIn all patients with active acromegaly, whether they had been treated or not, nadir GH in OGTT was >3 mU/I, whereas nadir GH was <1.88 mU/I in the cured patients and the control subjects. In patients with untreated active acromegaly IGF‐I, free IGF‐I, uGH and IGFBP‐3, but not uIGFBP‐3, were significantly higher than in healthy individuals (P<0.0001). Only IGF‐I values did not overlap with the control group. In those patients with acromegaly who had been treated but not cured these parameters overlapped with the control group. In patients with acromegaly there was a significant correlation between nadir GH levels in OGTT and IGF‐I (r=0.71), free IGF‐I (r=0.76, IGFBP‐3 (t=0.73) and uGH (r=0.81) (P<0.0001), but no correlation with uIGFBP‐3.CONCLUSIONSOnly be means of the OGTT could patients with active acromegaly be completely distinguished from the control subjects and from cured patients. IGF‐I, free IGF‐I, IGFBP‐3 and uGH were useful in the diagnosis of acromegaly, but of limited value in the follow‐up of acromegalic patients after treatment. The determination of free IGF‐I, which has yet not been investigated in acromegaly, offered no advantage over that of total IGF‐I and IGFBP‐3; uIGFBP‐3 was not useful in the diagnosis of acromegaly.
Diminished adrenal androgen secretion in familial glucocorticoid deficiency implicates a significant role for ACTH in the induction of adrenarche
Authors: Weber A. , Clark A. J. L. , Perry L. A. , Honour J. W. , Savage M. O. 
Published: November 2003

OBJECTIVE The mechanism of adrenarche is controversial, and there have been competing claims that its origin is in the hypothalamo‐pituitary axis or in the adrenal gland itself. ACTH is a proposed inducer of adrenarche so patients with ACTH resistance due to the familial glucocorticoid deficiency syndrome provide a model to clarify the degree to which ACTH is involved in the regulation of adrenal androgen secretion during adrenarche.DESIGN Random analysis of plasma adrenal androgens and urinary adrenal androgen output in treated patients with familial glucocorticoid deficiency.PATIENTS Eleven patients (6 males and 5 females, aged 6.5–21.6 years, 4 prepubertal, minimum bone age 9 years) with familial glucocorticoid deficiency were studied. In 6, mutations in the coding region of the ACTH receptor are the cause of their ACTH resistance. In the remaining 5 the receptor was normal.MEASUREMENTS Physical examination, basal serum cortisol, basal plasma ACTH, serum cortisol after stimulation with 250 μg ACTH(1–24), plasma dehydroepiandrosterone‐sulphate (DHEAS) and plasma androstenedione (A4), total urinary androgen excretion and single‐stranded sequencing of the coding region of the ACTH receptor.RESULTS DHEAS was undetectable in 8, and detectable but below the age‐matched reference values in 3 patients. A4 was measured in 10 patients, and in 3 patients (2 in late puberty) was found to be subnormal whereas in the remaining 7 patients A4 was normal for age and pubertal stage consistent with the gonadal contribution to peripheral A4 levels. Significantly diminished output of urinary adrenal androgen metabolites in 3 patients confirmed the results found in serum. The lack of adrenarche was independent of the presence of a mutation within the ACTH receptor and of the severity of glucocorticoid deficiency. Despite adequate glucocorticoid replacement therapy ACTH levels remained elevated in 10 of the 11 patients.CONCLUSIONS Although reduced adrenocortical inner zone cell number may contribute to the lack of adrenarche, in some patients there appears to be a discrepancy between partial glucocorticoid deficiency and significantly diminished adrenal androgen secretion. These data imply a significant contribution of ACTH to the regulation of adrenarche in normal children either by having a priming effect on the adrenal gland or by acting in concert with other adrenal androgen stimulating factors.