bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in pituitary response to GnRH during the luteal‐follicular transition of the human menstrual cycle
Authors: Messinis I. E. , Koutsoyiannis D. , Milingos S. , Tsahallna E. , Seferiadis K. , Lolis D. , Templeton A. A. 
Published: March 2008

SummaryOBJECTIVE We studied changes in pituitary response to GnRH during the luteal‐follicular transition of the human menstrual cycle.DESIGN Normally cycling women were investigated during two consecutive menstrual cycles. In each woman, GnRH tests were performed during the two LH surges and several times during the luteal‐follicular transition. Data for analysis were available in all women on days −8, −6, −4, −2, −1,1, 2, 3, 4, 5 and 7 in relation to the onset of second menstruation (day 1).PATIENTS Five normally ovulating parous women were studied.MEASUREMENTS Pituitary response to GnRH was calculated as the net increase in LH and FSH at 30 minutes (ΔLH and ΔFSH) above the basal value.RESULTS ΔLH and ΔFSH showed a similar pattern of significant changes during the luteal‐follicular transition. They decreased progressively from days −8 to 1 and increased on day 2. ΔLH and ΔFSH then decreased on days 3 and 4 and showed a further increase on days 5 and 7. In contrast to these changes, basal FSH levels increased from days −2 to 1 and remained high up to day 5, while basal LH levels showed a trend to increase only after the onset of menses.CONCLUSIONS These results demonstrate that the increase In basal FSH secretion during the luteal‐follicular transition is GnRH independent. It is suggested that LH and FSH release under the stimulation by GnRH is regulated by a common mechanism.
Control of prolactin‐secreting macroadenomas with parenteral, long‐acting bromocriptine in 30 patients treated for up to 3 years
Authors: Haase Roland , Jaspers Christian , Schulte Heinrich Maria , Lancranjan Ioana , Pfingsten Henrich , Orri‐Fend Miguel , Reinwein Dankwart , Benker Georg 
Published: March 2008

SummaryOBJECTIVE We investigated the effect of intramuscular injections of long‐acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS Thirty patients with PRL‐secreting pituitary macroadenomas were treated with repeated 4‐weekly intramuscular injections of 50 or 100 mg of a long‐acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n= 7), oral bromocriptine (7), and pituitary Irradiation (2). MEASUREMENTS A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection therafter. RESULTS In all patients PRL was suppressed from a mean ± SEM pretreatment level of 32 620 ± 8680 to 4480 ± 1140 mU/l on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/l) with the first to fourth injection, in three additional patients PRL levels normalized after 8–15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean SEM) decreased to 66 ± 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side‐effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0 6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site.CONCLUSION We conclude that long‐acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long‐term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections.
Pharmacokinetics of 1‐deamino‐8‐d‐arginine vasopressin after various routes of administration in healthy volunteers
Authors: Fjellestad‐Paulsen A. , Höglund P. , Lundin S. , Paulsen O. 
Published: March 2008

SummaryOBJECTIVE We investigated the pharmacokinetics and biological effects of 1‐deamino‐8‐d‐arginine vasopressin (dDAVP) in healthy adults after intravenous, subcutaneous, intranasal, peroral, sublingual and intrarectal administration.DESIGN Eight normal volunteers were studied over an 8‐hour period after each drug administration, separated by at least one week. For intravenous and subcutaneous administration, the subjects received 2 μg of dDAVP. The intranasal and sublingual doses were 20 μg and the rectal dose was 50 μ. Oral administration of dDAVP was effected with a 200‐μg tablet.MEASUREMENTS Plasma and urinary levels of dDAVP were measured using a specific and sensitive radioimmunoassay.RESULTS A significant increase of urine osmolality was observed after all routes of administration, except the sublingual and intrarectal for up to 8 hours after administration. After intravenous administration, the half‐life of elimination (t) of dDVAP was 78 ± 10 minutes. An extensive adsorption of dDAVP to the plastic syringe was found with intravenous but not with subcutaneous administration. Using the area under the curve of dDAVP from the subcutaneous administration as a reference, bioavailability was found to be 3.4% after intranasal administration and 0.1% after oral administration. After sublingual and intrarectal routes of administration no detectable dDAVP was found in the blood; however, low amounts were found in the total 24‐hour urine.CONCLUSION The bioavailability of dDAVP seems lower than previously reported after intranasal and oral administration.
Atrial natriuretic factor reduces vasopressin and angiotensin II but not the ACTH response to acute hypoglycaemic stress in normal men
Authors: Wittert G. A. , Espiner E. A. , Richards A. M. , Donald R. A. , Livesey J. H. , Yandle T. G. 
Published: March 2008

SummaryOBJECTIVE We determined the effects of physiological (non‐hypotensive) increments of plasma atrial natriuretic factor (ANF) on the vasopressin and hypothalamic‐pituitary‐adrenal response to insulin induced hypoglycaemia. DESIGN Single blind, placebo controlled, randomized study of the effect of vehicle alone or ANF (2.5 pmol/kg/min for 120 minutes) commencing 30 minutes before bolus administration of insulin (0 15 U/kg body weight).RESULTS ANF infusion raised venous plasma ANF levels four to five‐fold (mean level 32 ± 0.3 pmol/l at time of insulin injection) without affecting resting blood pressure or heart rate. After insulin, the fall in plasma glucose and rise in plasma adrenaline and noradrenaline were similar in both studies. In contrast, the responses in plasma arginine vasopressin (P < 0.02) and in plasma angiotensin II (P<0.05) were inhibited by ANF. Plasma corticotrophin releasing factor, ACTH and Cortisol responses to hypoglycaemic stress did not differ significantly in the presence and absence of ANF.CONCLUSION We conclude that four to five‐fold acute increase in plasma ANF, while attenuating vasopressin and angiotensin II responses to hypoglycaemia, does not inhibit the hypothalamic, pituitary and adrenal responses or inhibit sympathetic nervous activation in normal men.
Self‐administered subcutaneous human menopausal gonadotrophin for the stimulation of testicular growth and the initiation of spermatogenesis in hypogonadotrophic hypogonadism
Authors: Jones T. H. , Darne J. F. 
Published: March 2008

SummaryOBJECTIVE We determined whether or not self‐administered subcutaneous human menopausal gonadotrophin (hMG) therapy is safe and effective in the stimulation of testicular growth and initiation of spermatogenesis In men with hypogonadotrophic hypogonadism where human chorionic gonadotrophin alone had failed.DESIGN Human menopausal gonadotrophin was self‐administered subcutaneously in two dosage regimens to patients requiring (a) fertility (Group I), 37.5 IU twice daily (total weekly dose 525 IU) (n= 7) and (b) increased testicular size (Group II) 37.5 IU once daily (total weekly dose 265.5 IU) (n=2). Patients were assessed on a monthly basis.PATIENTS Nine patients with hypogonadotrophic hypogonadism were studied. Six patients had Idiopathic isolated hypogonadotrophic hypogonadism, one Kallman's syndrome, one idiopathic isolated hypogonadotrophic hypogonadism secondary to trauma and one with panhypopituitarism secondary to radiotherapy for a hypothalamic pituitary tumour. Five of these patients had a history of unilateral or bilateral cryptorchidism.MEASUREMENTS Semen analysis and serum testosterone. Testicular size was assessed by use of a Prader orchidometer.RESULTS Six of seven patients (four with a history of cryptorchidism) requesting fertility attained sperm counts of < 10 million/ml. Three pregnancies have been achieved so far. One failure occurred in a patient with a previous history of cryptorchidism. In Group I patients (a) with an initial testicular volume of 4 ml or less (n= 4), mean size increased from 3.25·0.9 (SD) ml to 12.2·3.8 ml, (b) an initial testicular volume of <4 ml mean size (n= 3) increased from 9.2 ± 3.9 ml to 10.3 ± 4 ml. In Group II (n= 2) testis size increased from a mean of 3.0 ± 1.4 ml to 9.0 ± 1.4 ml over a 6‐months treatment period.CONCLUSION Self‐administered subcutaneous human menopausal gonadotrophin is a safe and effective mode of therapy in increasing testicular size and inducing spermatogenesis in males with hypogonadotrophic hypogonadism.
Molecular forms of parathyroid hormone‐related protein in tumours and biological fluids
Authors: Bowden S. J. , Hughes S. V. , Ratcliffe W. A. 
Published: March 2008

SummaryOBJECTIVE We investigated the content and compared the molecular forms of parathyroid hormone‐related protein in tumour tissue, plasma and pleural fluid.DESIGN Measurement of parathyroid hormone‐related protein in tumour extracts and biological fluids and comparison of the elution profiles of parathyroid hormone‐related protein (PTHRP) immunoreactivity following gel filtration chromatography on Bio‐gel P100.PATIENTS Tumours and plasma from patients with humoral hypercalcaemia of malignancy were studied, together with tumours and pleural fluids from patients who were normocalcaemic.MEASUREMENTS Immunoreactivity in column fractions, plasma and tumour extracts was measured by a highly sensitive immunoradiometric assay for PTHRP 1–86 with specificity directed at the 17–61 region of PTHRP.RESULTS Similar levels of PTHRP immunoreactivity were measured in tumours from normocalcaemic and hyper‐calcaemic patients. PTHRP 1–86 (28–4630 fmol/g) was detected in eight of the nine tumours studied. Immunoreactivity in tumour extracts eluted as major peaks in the range 22–33 kDa with an additional peak of 15 kOa in three out of six tumours studied. In contrast, immunoreactivity in plasma and pleural fluid eluted within the range 7–14 kDa.CONCLUSIONS The major species of parathyroid hormone‐related protein in plasma and pleural fluids was consistently smaller than that in tumour tissue (22–33 kOa) suggesting that tumour‐derived parathyroid hormone‐related protein is processed at the COOH‐terminus to form a species of approximately 10 kDa which circulates in patients with humoral hypercalcaemia of malignancy.
Inhibin and follicle‐stimulating hormone levels in gonadotroph adenomas: evidence of a positive correlation with tumour volume in men
Authors: Lahlou Najiba , Le Nestour Elisabeth , Chanson Philippe , Seret‐Bégué Dominique , Bouchard Philippe , Roger Marc , Warnet André 
Published: March 2008

SummaryOBJECTIVE Gonadotroph adenomas are generally revealed by symptoms of mass effect at the stage of macroadenoma. Most of them hypersecrete FSH and/or gonadotrophin subunits. Rarely they hypersecrete LH, which could induce endocrinological symptoms. As the glycoprotein inhibin is secreted by the gonads under FSH control, we have evaluated whether high immunoreactive inhibin (IINH) levels correlated with FSH hypersecretion and whether IINH and FSH levels were related to tumour volume in subjects with gonadotroph adenomas.PATIENTS Forty‐five patients (30 men, 15 women) were retrospectively selected on the basis of immunostaining technique using specific antibodies raised against FSH‐beta, LH‐beta and glycoprotein alpha‐subunit.MEASUREMENTS Immunoreactive inhibin (IINH) was measured by radioimmunoassay using antiserum 1989 raised to bovine inhibin. Tumour volume index was the product in cm3 of length, width and height of the adenoma as assessed by computerized tomography.RESULTS In men (age 21–61 years), IINH levels were positively correlated with FSH levels (Spearman's r=0.67, P < 0.001), and both IINH and FSH levels were significantly correlated with tumour volume index (Spearman's r= 0.38, P<0.05 and r=0.39, P<0.05 respectively). In the subgroup of men with normal FSH levels (n= 17), the correlation of FSH with tumour volume index was high: Spearman's r= 0.56, P< 0.05. In the post‐menopausal women (n= 8, age < 55 years), IINH levels were undetectable or below the follicular phase range regardless of FSH values. In the premenopausal women (n= 7, age 22–49 years, follicular phase or amenorrhoea) IINH levels were above follicular phase range in three women including one who had very high FSH levels.CONCLUSIONS These data show that in men with gonadotroph adenoma FSH levels are related to tumour mass and suggest that a significant part of circulating FSH in patients with normal FSH levels arises from the tumour. The significant correlation between IINH and FSH levels demonstrates that tumoral FSH is bioactive and that high IINH levels do not exert any feedback control on tumoral FSH secretion. Therefore the coexistence of high FSH levels with high IINH levels is strongly suggestive of a gonadotroph adenoma. Gonadotroph adenomas seem to represent a unique model of long‐term FSH stimulation of Inhibin‐producing cells, in some way analogous to that created by repetitive administration of exogenous FSH.
Prevalence of subclinical hyperthyroidism and relationship between thyroid hormonal status and thyroid ultrasonographic parameters in patients with non‐toxic nodular goitre
Authors: Rieu Max , Bekka Saïd , Sambor Boris , Berrod Jean‐Louis , Fombeur Jean‐Pierre 
Published: March 2008

SummaryOBJECTIVE Basal plasma T4, T3 and TSH concentrations are usually normal in patients presenting with non‐toxic nodular goitre. Using the evaluation of TSH response to TRH in a large series of such patients living In an area with normal iodine intake, we evaluated the prevalence of subclinical hyperthyroidism and the relationship between thyroid hormonal status and ultrasonographic parameters.PATIENTS A prospective study of 242 consecutive patients (group I), referred with non‐autoimmune nodular goitre, normal plasma free T4, total T3 and TSH levels, without (subgroup IA, 222 patients) or with (subgroup IB, 20 patients) clear‐cut autonomous area(s) on scintigraphy. These patients were compared to 135 controls (group II).MEASUREMENTS Plasma free T4 (FT4), total T3 (T3T) and TSH measurements. Evaluation of TSH response to TRH (A level of increased TSH = peak TSH level during TRH test‐basal TSH level), thyroid scintigraphy and morphological characteristics (number and total volume of nodule(s) and volume of extranodular tissue) determined by ultrasonography.RESULTS In subgroup IA, (1) the mean (± SEM) basal TSH level (0.94± 0.04 μ/l) and the mean value of increased TSH after TRH (4.92 ± 0.34 μ/l) were lower (P<0.001) than in group II (1.28 ± 0.05 μ/l and 7.24 ± 0.25 μ/l, respectively). The prevalence of SH (Δ level of increased TSH below the mean – 3 SD in controls) was 17.2%; (2) the mean FT4 level and the mean T3T value were not different (P>0 05) from those of group II. In subgroup IB, (1) the mean basal TSH level (0.57 ± 0.11 μ/l) and the mean Increment of TSH after TRH (2.81 ± 0.62 μ/l) were lower (P < 0001) than in subgroup IA. The prevalence of subclinical hyperthyroidism was 750%; (2) the mean FT4 level (17.2± 0.9 pmol/l) was not different from that in group II. However, the mean T3T value (1.99 ± 0.01 nmol/l) was higher (P< 0.001) than in group II (1.65 ± 0.05). In group I, subgroup IA and IB, there were significant (P< 0.05, at least) correlations between the numbers of nodules and both basal TSH levels and Δ values of increased TSH or FT4 levels or T3T values. No correlations were found between other ultrasonographic data and plasma thyroid parameters.CONCLUSIONS This study demonstrates a high prevalence of subclinical hyperthyroidism in patients presenting with non‐toxic nodular goitres and suggests that the number of nodules, but not their total volume, is an important factor in the development of this condition.
Serious, prolonged hypoglycaemia with glibenclamide in a patient with Mendenhall's syndrome
Authors: Kumar S. , Boulton A. J. M. 
Published: March 2008

SummaryMendenhall's syndrome, characterized by familial insulin resistant diabetes, pineal hyperplasia and multiple somatic abnormalities, is associated with defects involving the a‐subunit of the insulin receptor. The associated insulin‐resistant diabetes is extremely difficult to treat; insulin is required in very large doses to control hyperglycaemia and oral hypoglycaemic agents are ineffective. We report a case of severe, prolonged hypoglycaemia that occurred in a 24‐year‐old patient with Mendenhall's syndrome following therapy with glibenclamide. He had glibenclamide 10 mg daily for 1 week following which he was admitted to hospital in hypoglycaemic coma with blood glucose levels < 1 0 mmol/l. This subject had undergone hypophysectomy at the age of 11 years. Prior to pituitary ablation, oral hypoglycaemic agents did not improve glycaemic control. Thus, previous hypophysectomy in this patient appears to have made it possible for glibenclamide to exert its hypoglycaemic effect. The occurrence of hypoglycaemia in this patient suggests alternative mechanisms for insulin action in conditions characterized by severe insulin resistance due to insulin receptor defects.
17‐Hydroxyprogesterone response to buserelin testing in the polycystic ovary syndrome
Authors: Şahin Yilmaz , Keleştimur Fahrettin 
Published: March 2008

SummaryOBJECTIVE We determined the 17‐hydroxyprogesterone (17‐OH P) response to buserelin, a GnRH agonist, and its relation to ovarian volume in the patients with polycystic ovary syndrome (PCOS).DESIGN We compared 17‐OH P response to buserelin in a large group of patients with that In a control group of healthy women. We also investigated whether there is any relation between LH‐induced 17‐OH P production in response to buserelin and ovarian volume.PATIENTS Ten normal women and 31 women with PCOS were included in the study.MEASUREMENT Pelvic ultrasound examination by abdominal or vaginal transducer was performed. Serum basal levels of LH, FSH, free testosterone and 17‐OH P were measured by radioimmunoassay. 17‐OH P responses to both ACTH and buserelin were detected. Cortisol levels were measured before and after dexamethasone suppression.RESULTS The subcutaneous administration of 1 mg buserelin produced an increase in serum 17‐OH P, which peaked within 24 hours in all groups. The mean ±SEM level of 17‐OH P, 24 hours after buserelin stimulation in the women with PCOS (15.94 ±1.31 nmol/l) was significantly higher (P<0001) than in the control group (6 75±0 69 nmol/l). The women with PCOS had increases in 17‐OH P levels exceeding 10.15 nmol/l 24 hours after buserelin testing. The increased 17‐OH P responses to buserelin were unchanged by pretreatment with dexamethasone to suppress adrenal function. The 17‐OH P response was significantly related to ovarian volume (r= 0.53, P<0.01).CONCLUSIONS Our findings suggest that the serum 17‐OH P response to a 1‐mg subcutaneous test dose of buserelin may be a diagnostic and practical test for PCOS. Increased ovarian volume in PCOS may be responsible for the elevated 17‐OH P response to buserelin, a GnRH agonist, at least in some patients.
Circadian variation in serum free and non‐SHBG‐bound testosterone in normal men: measurements, and simulation using a mass action model
Authors: Cooke R. R. , McIntosh J. E. A. , McIntosh R. P. 
Published: March 2008

SummaryOBJECTIVE We measured the changes in testosterone fractions in serum of normal men over a 24‐hour period, and determined whether they could be simulated on the basis of current understanding of the interactions betwen steroids and binding proteins in the blood.DESIGN Starting from between 0830 and 0930 h, blood samples were taken every 45 minutes for 25 5 hours.PATIENTS Five healthy males aged 26‐45 years. All participants worked on a hospital campus and while being sampled carried out their normal activities during waking hours.MEASUREMENTS The concentrations of testosterone (RIA) and albumin, and the percentage non‐sex hormone binding globulin‐bound testosterone (ammonium sulphate precipitation) and percentage free testosterone (rate dialysis), were measured on each sample. Cortisol (RIA) and sex hormone‐binding globulin (SHBG) (IRMA) concentrations were measured on every second sample, and that of corticosteroid‐binding globulin on two samples from each series.RESULTS In all participants the levels of free and non‐SHBG‐bound testosterone in early morning samples (near 0530 h) were significantly different from those taken before midnight (P< 0 0005). Significant circadian rhythms (P<0 05) in the concentration of testosterone and in the level of the free fraction were detected in all participants, and in four of the five participants for the non‐SHBG‐bound fraction. The amplitude of the free testosterone rhythm (34 ± 2% of basal) was greater than that for testosterone itself (24 ± 3% of basal). The 24‐hour rhythm of the non‐SHBG‐bound fraction was similar to the total and free fractions except for the period 0330‐0900 h when the level of this fraction declined by 15‐45% over 1 5‐3 hours. This decline was coincident with the initial rise in the concentration of Cortisol. A decline of 10 5 ± SEM 1 0% in the concentration of albumin, and 12 0 ± 1 1 % in that of SHBG occurred when the mean ambulant and supine levels were compared; analysis indicated significant circadian rhythms in the concentrations of these proteins. Simulation was used to investigate possible causes for the circadian rhythms in free and non‐SHBG‐bound testosterone. Simulation results matched the measured data well in qualitative terms, but quantitatively there were differences.CONCLUSIONS Increasing saturation of the binding proteins following rises in testosterone production, and the small but significant changes in protein concentration, probably related to postural changes, were implicated as the major factors in the rhythm amplitude. However, the early morning decline in the non‐SHBG‐bound fraction was not explained by these factors. The rise in Cortisol concentration at this time is a probable cause. Alternatively, simulation suggests that a substance appearing in the early morning and competing with testosterone for albumin binding sites may be responsible.