bluuebunny/crossref_metadata_2025_split huggingface dataset:
The hypothalamo‐pituitary‐adrenal axis across the normal menstrual cycle and in polycystic ovary syndrome
Authors: Stewart P. M. , Perm R. , Holder R. , Parton A. , Ratcliffe J. G. , London D. R. 
Published: March 2008

SummaryOBJECTIVE We explored the hypothesis that activation of the hypothalamo‐pituitary‐adrenal axis is involved in the pathogenesis of hyperandrogenism in the polycystic ovary syndrome.PATIENTS Seven women with polycystic ovary syndrome (mean age 27.6 ± 1.6 (SEM) years) (hirsutism, oligo/ amenorrhoea and elevated serum testosterone and dehydroepiandrosterone sulphate) and nine normal female controls (mean age 24.6 ± 15 years) were studied. To exclude anovulation as a confounding factor, four of these normal women were studied in both the follicular and luteal phase of the menstrual cycle.DESIGN AND MEASUREMENTS Plasma ACTH and Cortisol levels were measured at 15‐minute intervals between 0600 h and 1800 h. ACTH and Cortisol mean levels, pulse number and amplitude were calculated using established computer software, programmed to identify ACTH and Cortisol peaks.RESULTS With the exception of mean plasma levels of ACTH over the 12‐hour period, which were reduced in the luteal phase of the menstrual cycle (1.8 ± 0.3 pmol/l) compared to the follicular phase (2.3 ± 0.2 pmol/l, P < 005), there were no differences in the pattern of ACTH or Cortisol secretion across the normal cycle. In polycystic ovary syndrome, 12‐hour ACTH pulse frequency was reduced (3.6 ± 0 7) compared with controls (5.9 ± 0.6, P<0.05), but Cortisol pulsatility and ACTH and Cortisol mean levels were similar in both groups.CONCLUSION The hyperandrogenism of polycystic ovary syndrome cannot be explained by enhanced ACTH secretion. Normal circulating Cortisol levels, yet elevated dehydroepiandrosterone sulphate levels, suggests that polycystic ovary syndrome is yet another example of discrepant adrenal glucocorticoid and androgen secretion, and provides further evidence for a putative adrenal androgen stimulating factor.
The effects of oxandrolone on the growth hormone and gonadal axes in boys with constitutional delay of growth and puberty
Authors: Malhotra A. , Poon E. , Tse W.‐Y. , Pringle P. J. , Hindmarsh P. C. , Brook C. G. D. 
Published: March 2008

SummaryOBJECTIVE We studied the effects of oxandrolone on serum concentrations of LH, FSH, testosterone, GH, SHBG, DHEAS, IGF‐I and insulin in boys with constitutional delay of growth and puberty.DESIGN Ten boys with constitutional delay of growth and puberty, mean age 138 years (range 12 4‐15‐5) were studied. Twenty‐four‐hour serum concentration profiles of GH, LH and FSH were constructed by drawing blood samples at 20‐minute intervals. Three study occasions over a period of 6 months were chosen to assess hormone concentrations before, during and 6 weeks after a 3‐month course of oxandrolone (2–5 mg once daily) therapy.RESULTS Growth velocity increased during oxandrolone treatment and stayed higher after therapy (pre 3.9 ± 0.5; on 6.3 ± 0.8; post 6.4 ± 0.9 cm/year (mean±SEM) two way ANOVA, F=5.3, P= 0.02). Oxandrolone had androgenic effects, suppressing mean serum LH concentrations from 1.7 ± 0.3 to 1.1 ± 0.2 U/I and serum testosterone concentrations from 1.9 ± 0.6 to 0.8 ± 0.1 nmol/l. SHBG concentrations were also reduced from 130.9 ± 14.6 to 307±73 nmol/l. Serum GH concentration fell slightly from 5.9 ± 0.6 to 4.8 ± 0.5 mU/l. After cessation of treatment, there was a significant‘rebound’in mean 24‐hour serum LH (2.6 U/l ± 0.4) and testosterone concentrations (3.2 ± 0.9 nmol/ l) but no change in serum GH concentrations. SHBG values also rose but not to the same extent as those observed before therapy (82.0 ± 84 nmol/l). There were no statistically significant differences in serum concentrations of FSH, DHEAS, IGF‐I and insulin over the study period.In a stepwise multiple regression analysis of factors that might influence the growth rate observed, the 24‐hour mean serum testosterone concentration and the treatment (on or off) with oxandrolone were the main influences. The relationship was described by the equation Height velocity = 0.69 (24‐hour mean serum testosterone concentration) +1 70 (treatment regimen) + 3.37 (adjusted R2= 0.35, F= 8.39, P= 0.001).CONCLUSIONS Oxandrolone has an androgenic action as shown by changes in serum LH, testosterone and SHBG concentrations and by the lack of effect on FSH. No effect of oxandrolone on the GH axis was documented. We suggest that the growth promoting effects of oxandrolone are related in part to the mild androgenic effects of the steroid and the growth acceleration following oxandrolone withdrawal may reflect increasing total serum testosterone concentrations and decreasing levels of SHBG and progress in puberty.
Effect of 131 I treatment on the calcitonin response to calcium infusion in hyperthyroid patients
Authors: Tzanela M. , Thalassinos N. C. , Nikou A. , Georgiadis G. , Philokiprou D. 
Published: March 2008

SummaryOBJECTIVE The objective was to evaluate the effect of 131I treatment for hyperthyroidism on calcitonin secretion by thyroid C‐cells.DESIGN Determination of basal calcitonin levels and calcitonin secretory reserve before and aiter 131I administration.PATIENTS Seventeen hyperthyroid patients (15 female, two male) were studied before, and 2 months after 131I treatment, and 12 of these patients were restudied 8 months after 131I treatment.MEASUREMENTS Calcitonin response was assessed by measuring basal and post calcium infusion calcitonin levels. Basal TSH, T3, and T4 levels were also determined at each study.RESULTS The rise of plasma calcium resulted in statistically significant increase of plasma calcitonin levels before 131I treatment (10.9·2.4 pmol/l), while this response was significantly diminished 2 and 8 months after treatment (2.6·0.7 and 1.6·0.3 pmol/l, respectively). No correlation was found between the calcitonin response and age or plasma TSH.CONCLUSION Our results demonstrate that 131I treatment for hyperthyroidism may seriously damage thyroid C‐cells and cause calcitonin deficiency.
Cross‐sectional and longitudinal study of the pituitary‐thyroid axis in patients with thalassaemia major
Authors: Landau H. , Matoth I. , Landau‐Cordova Z. , Goldfarbs A. , Rachmilewitz E. A. , Glaser B. 
Published: March 2008

SummaryOBJECTIVE AND DESIGN Thyroid dysfunction is known to occur frequently In thalassaemla major, but Its prevalence and severity varies in different cohorts, and the long‐term natural history is poorly described. We evaluated the pituitary/thyroid axis in thalassaemia major patients in a cross‐sectional study and correlated abnormalities with indices of iron overload. Furthermore, the course of thyroid disease in thalassaemia major patients was assessed In a 15‐year longitudinal study.PATENTS AND MEASUREMENTS Cross‐sectional study: pituitary‐thyroid axis function was examined in 37 patients (22 F, 15 M; aged 10–39 years, mean ± SE = 21 ± 1.4) out of a total of 43 who attended the Haematology and Endocrinology Clinics of Hadassah Hospital on a regular basis. The mean pretransfusion Hb level was 85·20 g/l, and all patients except one were treated with desferrioxamine (DF, mean SE dose 20.2·2.6 mg/kg/day). Twenty‐two had hypogonadotrophic hypogonadism (HH). Longitudinal study: 21 thalassaemia major patients were evaluated with TRH tests in 1976 and again in 1985. Fourteen of these and another eight were evaluated in both 1985 and 1991. RESULTS Cross‐sectional study: no patient had any clinical signs or symptoms of hypothyroidism; however, one had abnormally low T4, borderline low FT4 and normal T3 levels associated with an exaggerated TSH response to TRH consistent with mild hypothyroidism. This patient did not have a previous TRH test, but serial basal determinations over 7 years revealed a progressive decrease in thyroid function. Thirty‐six patients had thyrold hormone levels within the normal range. Nine of these (24.3%) had only an exaggerated TSH response to TRH whereas seven others (19%) also had borderline elevated basal TSH levels. TSH response to TRH was not correlated with age, serum ferrltin or liver function tests (ALT or GGT). Longitudinal study: mean TSH response to TRH decreased (P >0.002), and mean T3 levels Increased (P >0.001) between 1975 and 1985. These findings are probably related to the initiation of DF treatment in 1981. During the last 6 years, four patients with previously normal TSH responses to TRH developed elevated peak TSH levels. Mean T3 concentrations decreased and TSH response to TRH increased significantly (P >0.001 for both).CONCLUSIONS (1) In this patient group the thyroid pituitary axis is less sensitive than the gonadal axis to iron‐induced damage; only one out of 37 patients developed mild uncompensated hypothyroidism. (2) As opposed to the gonadal axis, the thyrold gland appears to fail before the central components of the axis. (3) Abnormal thyroid function may be reversible in the early stages. (4) Progression is variable, and it may take years to progress from normal to uncompensated hypothyroidism.
Assessment of endocrine function after transsphenoidal surgery for Cushing's disease
Authors: McCance D. R. , Gordon D. S. , Fannin T. F. , Hadden D. R. , Kennedy L. , Sheridan B. , Atkinson A. B. 
Published: March 2008

SummaryOBJECTIVE We assessed the endocrine outcome after transsphenoidal surgery for Cushing's disease.DESIGN Five‐year (mean) follow‐up (range 1 month‐12 years) of patients undergoing transsphenoidal surgery for Cushing's disease between 1977 and 1990; review of case notes, current clinical and biochemical assessment including 24‐hour urinary free cortisol.SETTING Northern Ireland.SUBJECTS Forty‐one patients (33F:8M); mean age at dlagnosls 39 1 years (9–72 years).MAIN OUTCOME MEASURES Measurements of early post‐operative 0800 h serum cortisol and 24‐hour urinary free cortisol at least 24 hours after withdrawal of oral hydrocortisone therapy. This was followed by low dose dexamethasone testing. Current 24‐hour urinary free cortisol measurements. Retrospective definition of cure.RESULTS Twenty‐seven patients were either cured or improved by surgery, 14 were considered definite failures.Of 19 patients cured, eight had unmeasurable early postoperatlve 0800 h serum cortisol levels while of 15 tested, 13 had complete suppression with dexamethasone and two suppressed normally but to still measurable levels (39 and 60 nmol/l respectively). Seventeen patients in total have subsequently had bilateral adrenalectomy of whom two have developed Nelson's syndrome. Seven of the 41 patients were shown to have definite cyclical cortisol secretlon first diagnosed post‐operatively in three patients. Hormone deficiency included TSH (5), LH/FSH (1), cortisol (1) and ADH (temporary in 7, permanent in 1). In all, seven patients had some type of permanent hormonal deficiency post‐operatively.CONCLUSIONS Transsphenoidal surgery offers a worthwhile cure rate without the necessity of life‐long endocrine therapy. Post‐operative endocrine assessment must be rigorous so that early further management can be planned in the significant percentage of patients in whom cure is not achieved. Early complete suppression on low dose dexamethasone testing is very suggestive of cure but repeated and long‐term monitoring of 24‐hour urinary free cortisol is advisable.
The frequency and amplitude of growth hormone secretory episodes as determined by deconvolution analysis are increased in adolescents with insulin dependent diabetes mellitus and are unaffected by short‐term euglycaemia
Authors: Pal B. R. , Matthews D. R. , Edge J. A. , Mullis P. E. , Hindmarsh P. C. , Dunger D. B. 
Published: March 2008

SummaryOBJECTIVE High overnight plasma growth hormone (GH) levels in insulin‐dependent diabetes mellitus (IDDM) are reflected in both an increase in the GH pulse amplitude and elevated baseline GH concentrations. To determine whether these are a result of an increase in GH secretory episodes, we undertook deconvolution analysis of overnight GH profiles using previously determined half‐life data.DESIGN Deconvolution of overnight GH profiles (2000–0800 h) was undertaken from normal and diabetic adolescents (either on their usual insulin regime (n= 15), during overnight euglycaemic clamp using a variable rate insulin infusion (n= 29), or during clamp plus 100 mg pirenzepine to suppress endogenous GH (n= 7)).PATIENTS Thirty‐five normal and 29 diabetic adolescents of both sexes at all stages of puberty.MEASUREMENTS GH secretory rates were calculated from deconvolution analysis, and Fourier transformation was used to determine dominant pulsatility.RESULTS In diabetic subjects on their usual regime, there was increased mean overnight GH secretion when analysed by sex and by puberty stage compared to normal subjects; overnight OH secretion median (range) of diabetic group 1.48 (0.56–3.81) mU/min; control group 0.62 (0.32–1.92) mU/min (P>0 001). Fourier transform analysis of these secretory episodes showed greater pulse frequency in the diabetics with dominant pulse periodicity of 90 minutes compared with 135 minutes in normal subjects.During overnight euglycaemia, mean ± SEM overnight GH secretory rates were comparable to subjects' usual regime night (1.82 ± 0.33 vs 1.91 ± 0.37 mU/min) and there was no change in the dominant pulse periodicity of 90 minutes. Pirenzepine administration in diabetic subjects significantly reduced overnight GH secretion from 1.57 ± 0.19 to 0.71 ± 0.80 mU/min (P> 0.001) showing a median (range) reduction of 63 (9.3–82. 8)% when compared to the subjects' clamp night. However, dominant pulse periodicity was not altered by pirenzepine administration, and remained at 90 minutes.CONCLUSION In patients with insulin‐dependent diabetes mellitus there is an increase in both the amplltude and frequency of pulsatile GH secretion compared to normal subjects, which is not affected by maintenance of overnight normoglycaemia. The anticholinergic drug pirenzepine appears to suppress the amplitude of GH pulse secretion but has no effect on frequency.
Congenital hypothyroidism: the Riyadh Military Hospital experience
Authors: Majeed‐Saidan M. A. , Joyce Brian , Khan Masood , Hamam Hisham D. 
Published: March 2008

SummaryOBJECTIVE We aimed to find out the incidence of primary congenital hypothyroidism (CH) among infants born within the Riyadh Al‐Kharj Hospital Programme in addition to early detection and treatment of these infants.DESIGN All babies born within the Riyadh Al‐Kharj Hospital Programme were screened by cord blood TSH. Blood spot TSH were done in the majority of infants between 2 and 5 days after birth. All suspected cases were recalled for confirmatory tests. 123I thyroid scan and X‐ray of the knee and maternal blood for thyroid antibodies were done for confirmed cases.MEASUREMENTS A cut off TSH level of 30 mlU/l for cord blood and 25 mlU/l for spot blood were used. All samples were assayed by immunoassay methods.RESULTS 44778 (99.4% of the total births) infants were screened. Twenty‐five cases were detected, four of which were excluded. The incidence of primary congenital hypothyroidism was 1/2096. Five cases were missed on the initial screen. Eight out of 17 children who had 123I thyroid scan were found to have dyshormonogenesis. Associated malformation and diseases were diagnosed in 42.85%. Two had chromosomal anomalies; ring chromosome 9 has not been previously reported in association with congenital hypothyroidism.CONCLUSION The incidence of congenital hypothyroidism, dyshormonogenesis and the associated malformations and diseases are higher than those reported in the literature. Cord blood as a screening method is associated with a significant number of missed cases.
PCR analysis and sequencing of the SRY sex determining gene in four patients with bilateral congenital anorchia
Authors: Lobaccaro Jean‐Marc , Medlej Rita , Berta Philippe , Belon Charles , Galifer René‐Benoit , Guthmann Jean‐Paul , Chevalier Catherine , Czernichow Paul , Dumas Robert , Sultan Charles 
Published: March 2008

SummaryOBJECTIVE We explored the possibility of a genetic anomaly in the sex determining region of the Y chromosome, SRY gene, known to be equated to the testis determining region.PATIENTS Four patients with bilateral congenital anorchia, absence of testicular tissue, elevated FSH and a lack of testosterone response to human chorionic gonadotropin stimulation tests were studied.MEASUREMENTS Amplification by polymerase chain reaction of the SRY gene and direct double stranded DNA sequencing were performed with the same primers.RESULTS The expected 648 basepairs band of SRY was detected in the four DNA samples from patients with bilateral congenital anorchia. Direct sequencing did not show any difference with the previous published sequence.CONCLUSIONS These data suggest that, in the four patients, bilateral congenital anorchia is not related to an anomaly of the opening reading frame sequence of the SRY gene.
Hyperinsulinaemia in the polycystic ovary syndrome confirmed with a specific immunoradiometric assay for insulin
Authors: Conway Gerard S. , Clark P. M. S. , Wong D. 
Published: March 2008

SummaryOBJECTIVE Hyperinsulinaemia in the polycystic ovary syndrome (PCOS) has previously been defined using polyclonal radioimmunoassays (RIA) in which partially processed insulin‐like molecules cross‐react. This study aimed to reassess hyperinsulinaemia in women with PCOS using specific immunoradiometric assays (IRMA) for insulin, proinsulin and 32–33 spilt proinsulin.DESIGN Patients attended for 75 g oral glucose tolerance tests and were divided into groups depending on their degree of obesity and fasting insulin status determined by RIA. IRMA measurements for insulin‐like molecules in plasma from patients with PCOS and controls were compared.PATIENTS Thirty‐four patients with ultrasound diagnosed PCOS presented to a reproductive endocrinology clinic. A control group comprised women with normal ovaries on ultrasound. Four groups were constructed, two with normal fasting insulin concentrations (lean PCOS and controls) and two with hyperinsulinaemia (lean and obese PCOS).MEASUREMENTS Plasma glucose, insulin (RIA and IRMA), proinsulin and 32–33 split proinsulin concentrations were measured at time 0, 30 and 120 minutes of an oral glucose tolerance test.RESULTS Hyperinsulinaemia determined by RIA in lean and obese women with PCOS was confirmed using a specific IRMA assay for insulin. Plasma proinsulin and 32–33 split proinsulin concentrations were higher in hyper‐insullnaemic women with PCOS compared with women with normal insulin concentrations. The proportion of circulating insulin‐like molecules represented by proinsulin and 32–33 split proinsulin was similar in all groups studied.CONCLUSIONS Hyperinsulinaemia in PCOS is likely to reflect insulin resistance because the raised concentrations of proinsulin and 32–33 split proinsulin were in proportion to the raised insulin concentrations. Hyperinsulinaemia in PCOS, defined by RIA, therefore differs from that in non‐Insulin dependent diabetes mellitus where it Is largely accounted for by disproportionate hyperproinsulinaemla.
Influence of spontaneous or induced puberty on the growth promoting effect of treatment with growth hormone in girls with Turner's syndrome
Authors: Massa Guy , Maes Marc , Heinrichs Claudine , Vandeweghe Mark , Craen Margarita , Vanderschueren‐Lodeweyckx Magda 
Published: March 2008

SummaryOBJECTIVE The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turner's syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH.PATIENTS AND DESIGN The investigation was performed in 36 girls with Turner's syndrome treated for 3 years with rhGH in a dose of 1 IU/kg week, administered as daily subcutaneous injections. Fifteen patients remained prepubertal throughout the observation period (Group 1). During the first 2 years of rhGH therapy, four girls developed puberty spontaneously (Group 2). During the 3rd year of rhGH treatment puberty was induced with 100 ng/kg day ethinyl oestradlol orally in 17 girls requesting pubertal development and with a bone age of at least 11‘years' (Group 3).RESULTS During the first year of rhGH therapy height velocity increased significantly in all patients. Mean ± SD height velocity was higher in the four patients with Turner's syndrome who developed spontaneous puberty than in 17 age‐matched girls with Turner's syndrome without puberty (8.9 ± 1.2 vs 7.4 ± 12 cm/year; P < 0.05). During the second and third year of rhGH treatment height velocity decreased in all patients but remained above baseline levels. The induction of puberty with 100 ng/kg day ethinyl oestradlol in the patients of Group 3 did not lead to an acceleration of height velocity, but seemed in contrast to decelerate height velocity. After 3 years of rhGH treatment, 21 out of 36 patients have obtained a height at or above the initially calculated projected adult height and five girls are already taller than 150 cm.CONCLUSIONS The onset of spontaneous puberty during the first years of rhGH treatment seems to have an additive effect to rhGH on height velocity. Induction of puberty with oral administration of 100 ng/kg day ethinyl oestradiol did not have any beneficial effect on height velocity and seems therefore not to be the optimal way to induce puberty with an adequate pubertal growth spurt in girls with Turner's syndrome under rhGH therapy. Different doses and routes of oestrogen administration have to be evaluated in order to mimic the growth promoting effect of spontaneous puberty as well as possible.
Endothelin‐1 receptors in the human myometrium: evidence for different binding properties in post‐menopausal as compared to premenopausal and pregnant women
Authors: Schiff Eyal , Ben‐Baruch Gilad , Galron Ronit , Mashiach Shlomo , Sokolovsky Mordechai 
Published: March 2008

SummaryOBJECTIVE We investigated the binding properties of the endothelin receptors in the human myometrium in clinical situations associated with different ovarian steroid levels.SUBJECTS AND METHODS Binding properties of the endothelin receptors were studied in myometrial membranes from post‐menopausal women (n= 12), myomatous premenopausal women (n= 14) and pregnant women (n= 14), using 125I‐labelled endothelin‐1.RESULTS The mean (SD) maximal receptor density (Bmax) was significantly higher in samples from premenopausal and pregnant women than from post‐menopausal women (983 ± 196, 1116 ± 201 and 490 ± 145 pmol/g protein, respectively). Receptor affinity (Kd) did not differ significantly between these groups. Among the pregnant women, mean Bmax and Kd values were similar in those who electively underwent Caesarean section prior to the onset of labour and those operated on during the second stage of spontaneous labour. Binding properties of myometrial membranes of either pre or post‐menopausal women were unaffected by the presence of high levels of beta‐oestradiol or progesterone in the medium. Among samples of premenopausal women, no significant difference was found in binding properties between those operated on either during mid‐follicular phase or during mid‐luteal phase.CONCLUSIONS In clinical situations associated with relatively high levels of ovarian steroids, the density of endothelin receptors in the myometrium is higher than in situations associated with low ovarian steroid level. Ovarian steroids may exert their influence via the production of other mediators. Changes in density of the endothelin receptor, induced by change in ovarian steroids activity, might play a role in the regulation of myometrial contractility.