bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained suppression of serum LH, FSH and testosterone and increase of high‐density lipoprotein cholesterol by daily injections of the GnRH antagonist cetrorelix over 8 days in normal men
Authors: Behre Hermann M. , Böckers Anja , Schlingheider Annette , Nieschlag Eberhard 
Published: March 2008

SummaryOBJECTIVE Recently we have shown that single dose injections of the new GnRH antagonist cetrorelix ([Ac‐o‐Nal(2)1, D‐Phe(4CI)2, D‐Pal(3)3, D‐Cit5, D‐Ala10]GnRH; SB‐75) decrease serum LH and testosterone in a dose‐dependent manner in normal men. These results prompted us to investigate the effectiveness and safety of multiple daily injections of cetrorelix in normal male volunteers.DESIGN AND VOLUNTEERS Following two control examinations 16 young men were randomly assigned to four study groups (n= 4/group). Daily doses of 0 (placebo), 2, S, and 10 mg cetrorelix were injected subcutaneously at 0800 h for 8 days and morning and evening blood samples were obtained for 3 weeks.RESULTS One day after the first cetrorelix injection, serum LH and testosterone concentrations were significantly suppressed in all treatment groups. Whereas in the 2 and 5‐mg dose groups LH and testosterone showed some fluctuations, daily injections of 10 mg cetrorelix consistently suppressed LH and testosterone in all men. In addition, in this group serum FSH concentrations were significantly suppressed to subnormal values 1 day after the first injection and remained in this range up to 5 days after the last injection. A time and dose‐dependent increase of high‐density lipoprotein cholesterol was observed during cetrorelix‐induced testosterone deprivation with a maximal increase of 0 38*013 mmol/l (14 8 ±5 1 mg/dl; mean ±SEM) in the 10‐mg dose group. In addition, parallel to suppressed testosterone the volunteers' libido was significantly reduced under the GnRH antagonist. Apart from those symptoms caused by androgen deficiency, the only adverse side‐effect observed was a mild painless local erythema at the injection site that disappeared within an hour.CONCLUSIONS Daily injections of 10 mg cetrorelix effectively and consistently suppress serum LH, FSH and testosterone concentrations, and therefore it has potential for treatment of sex hormone‐dependent diseases and for male contraception.
Longitudinal study of maternal plasma bioavailable testosterone and androstanediol glucuronide levels during pregnancy
Authors: Kerlan Véronique , Nahoul Khalil , Le Martelot Marie‐Thérèse , Bercovici Jean‐Pierre 
Published: March 2008

SummaryOBJECTIVE The aim of this study to evaluate during normal pregnancy plasma bioavailable testosterone and androstanediol glucuronide levels.MEASUREMENTS Bioavailable testosterone, androstanediol glucuronide and SHBG levels were evaluated every 4 weeks from week 6 to week 38 in 10 normal pregnant women. We also measured plasma oestradiol, oestriol, Δ4‐androstenedione, 17‐hydroxyprogesterone, progesterone and testosterone.RESULTS The mean bioavailable testosterone levels were within the range of non‐pregnant women but with an increasing trend until delivery. Androstanediol glucuronide had increased at weeks 6 and 8, decreased at week 14, remained low at week 30, and increased again at week 34. SHBG was significantly correlated with testosterone, oestradiol and oestriol. No correlation could be established between androstanediol glucuronide and any other parameter.DISCUSSION Bioavailable testosterone (non‐SHBG bound testosterone) represents the sum of free testosterone plus albumin bound testosterone. The increase in testosterone concentrations with decreased albumin levels during pregnancy, could suggest reduced metabolic clearance of testosterone throughout pregnancy. No correlation was established between the decrease in androstanediol glucuronide and increase in progesterone, suggesting that the decrease in androstanediol glucuronide is not a consequence of the inhibitory effect of progesterone on 5α‐reductase activity.
Assessment of 5α‐reductase activity in hirsute women: comparison of serum androstanediol glucuronide with urinary androsterone and aetiocholanolone excretion
Authors: Gilad S. , Chayen R. , Tordjman K. , Kisch E. , Stern N. 
Published: March 2008

SummaryOBJECTIVE Recent evidence suggests that androstanediol glucuronide (AG), a metabolite of dihydrotestosterone (DHT) formed in skin, is frequently elevated in hirsute women, presumably reflecting enhanced 5a‐reductase activity. An alternative method of demonstrating 5a‐reductase activity is the androsterone (A)/aetiocholano‐lone (E) ratio in urine. A and E are the 5α‐ and 5β‐ reduced metabolites, respectively, of androstenedione, which is the principal metabolite of dehydroepiandrosterone (D). Although serum AG and the urinary A/E ratio have both been considered valid methods for assessing 5α‐reductase activity, the two have not been previously compared in hirsute women. The present study was undertaken to assess 5a‐reductase activity in hirsute patients as determined by these two different methods.PATIENTS AND MEASUREMENTS We surveyed 47 untreated women (ages 17–33) with various degrees of hirsutism. Serum testosterone, bioavailable testosterone, dehydroepiandrosterone sulphate, and AG were determined. Additionally, A, E and D were measured in 24‐hour collections of urine.RESULTS For the 47 women, 37 had elevated blood levels of AG (17.4 ± 2.2, mean±SEM; normal <8 nmol/l), but only 18 of these had an increased urinary A/E ratio (> 1.5). All but one of the remainder had elevated urinary and/or serum androgen levels. Overall, no significant correlation between AG and A/E was observed. There was a highly significant correlation between AG in serum and A in urine (r= 0.82, P<0 001). AG was also positively related to dehydroepiandrosterone sulphate (r= 0.64; P< 0.005), bioavailable testosterone (r= 0.6; P<0001), aetiocholanolone (r= 0.58; P<0 001) and total testosterone (r= 0.52; P& 0.01). In contrast, A/E was not significantly related to androgen production.CONCLUSIONS There is a poor correlation between AG and the A/E ratio in hirsute women. Although AG may be raised by increased 5α‐reductase activity, it is probably also affected by the presence of elevated androgens regardless of 5α‐reductase activity.
Clonal analysis of human adrenocortical carcinomas and secreting adenomas
Authors: Gicquel Christine , Leblond‐Francillard Marie , Bertagna Xavier , Louvel Albert , Chapuls Yves , Luton Jean‐Pierre , Girard François , Le Bouc Yves 
Published: March 2008

SummaryOBJECTIVES Adrenocortical tumours in man are characterized mainly on biochemical, anatomical and histological grounds which establish their secretory pattern and, with some uncertainty, their benign or malignant nature. To study further these tumours and eventually to shed some light on their pathogenesis, we determined their clonal composition.METHODS Clonal composition was determined by X‐chromosome inactivation analysis on tumour and leucocyte DNA using three markers: M27β, phosphoglycero‐kinase (PGK) and hypoxanthine‐phosphoribosyl transferase (HPRT) with 88, 33 and 27% heterozygosity rates respectively.PATIENTS Clonal analysis was performed on 25 tumours from 19 heterozygous female patients: four had a carcinoma, 14 had a single secreting adenoma, and one had autonomous bilateral macronodular hyperplasia with Cushing's syndrome (seven adenomas examined).RESULTS The malignant tumours had patterns indicative of monoclonality. The single adenomas displayed contrasting results with patterns indicative of monoclonality in eight cases, and patterns indicative of polyclonality in six cases; monoclonal adenomas were larger and had a higher prevalence of nuclear pleomorphism than the apparently polyclonal adenomas. In the patient with bilateral macronodular hyperplasia, different clonal patterns were present in different adenomas: whereas a clear monoclonal pattern was observed in the three adenomas of the right gland, in which the active X‐allele was not always the same, in two interpretable adenomas of the left gland, a moderately skewed pattern suggested a partial monoclonal component.CONCLUSIONS These data show that adrenocortical carcinomas are monoclonal and suggest that adenomas may arise from a single cell or from more than one cell under the putative action of local growth factors. In adenomas, which until now had appeared homogeneous, this genetic heterogeneity may reflect different pathophysiological mechanisms or it may represent different stages of a common multistep process exceptionally occurring in a single patient with bilateral macronodular hyperplasia.
Effect of hyperinsulinaemia on the function of the pituitary‐adrenal axis in healthy man
Authors: Walker M. , Berrish T. S. , James A. R. , Alberti K. G. M. M. 
Published: March 2008

SummaryOBJECTIVE Circulating insulin levels in themselves have been reported to influence the counter‐regulatory hormone response to hypoglycaemia in man. The effect of insulin on a specific aspect of this response was examined during euglycaemia by stimulating the pituitary‐adrenal axis with human corticotrophin‐releasing hormone (CRH).SUBJECTS Eight healthy males.DESIGN Following an overnight fast, insulin was infused at 15 (low) and 60 (high) mU/kg/h from 0900 h for 180 minutes on separate occasions in random order. On each occasion, blood glucose was clamped at euglycaemia, and 1 μ/kg/kg (i.v. bolus) human CRH was administered at 120 minutes.MEASUREMENTS Circulating hormone concentrations were determined by radioimmunoassay. Peak Cortisol and ACTH responses were compared for the two study conditions.RESULTS Mean serum insulin levels were threefold higher during the high compared with the low insulin infusion (mean difference 320 pmol/l, 95% confidence interval (CI) 150‐490, P<0001). Blood glucose levels during the clamps were comparable (mean difference 0 15 mmol/l, 95% CI 0‐0.63). Plasma Cortisol levels increased following CRH, although the peak concentration was significantly lower during the high insulin infusion (mean difference 36 nmol/l, CI 0‐110, P< 0.02). However, peak ACTH levels were comparable for the two insulin levels (mean difference 8 ng/l (1.8 pmol/l), CI 0‐50).CONCLUSIONS The peak Cortisol response to CRH was diminished at the higher circulating insulin levels. This was not dependent upon concurrent hypoglycaemia and did not appear to be mediated at the level of the pituitary gland.
Serum growth hormone (GH) profiles after nasally administered GH in normal subjects and GH deficient patients
Authors: Maller Jens , Lauersen Torben , Mindeholm Linda , Hoelgaard Annie , Ovesen Per , Jørgensen Jens O. L. , Christiansen Jens S. 
Published: March 2008

SummaryOBJECTIVE GH‐deficient patients are at present treated with daily subcutaneous GH injections. Further improvements in patient compliance and effects of treatment may occur with nasal administration. We have examined the absorption of nasally administered GH in healthy subjects and In GH deficient patients in two separate studies.DESIGN Healthy subjects and GH deficient patient were examined in the morning after an overnight fast. Twelve IU of GH in a powder containing didecanoyl‐l‐α‐phosphatidylcholine as enhancer were administered in the nostrils (6 IU in each nostril) at the beginning of the study in the healthy subjects. The GH deficient subjects received a total of 6 IU GH/m2 intranasally. Blood was frequently sampled for up to 4 hours. Before and after nasal application anterior rhinoscopy was performed.PATIENTS Eight normal subjects and 7 GH deficient patients.MEASUREMENTS Serum GH.RESULTS (mean ± SD) Mean maximum concentration (Cmax) in the normal group was 57.6 mU/l ± 36.9 with a mean time to obtain Cmax(Tmax) of 65 ± 47 min. In the GH deficient group Cmax was 56.1 ± 26.1 mU/l with a mean Tmax of 45 ± 15 min. The subjects did not report any major inconvenience during the study. Anterior rhinoscopy did not reveal changes.CONCLUSION Nasally administered GH is absorbed to a significant degree from the nasal mucosa without obvious untoward effects in the short term. These data encourage further studies with nasal GH administration.
Gynaecomastia caused by a primary mediastinal seminoma
Authors: Nagi Dinesh K. , Jones William G. , Belchetz Paul E. 
Published: March 2008

SummaryThe case of a young man aged 26 is reported. He presented with a short history of painful gynaecomastia, and no other associated symptoms. Radiological investigations showed a mass in the anterior mediastinum. Endocrine investigations showed high circulating oestradiol and high hCG‐β levels. There was no evidence of primary testicular tumour or metastases. Surgical removal of the mediastinal mass led to normalization of oestradiol and hCG‐β levels and regression of gynaecomastia. Histology showed the tumour to be a primary mediastinal seminoma staining positively for hCG‐β Further treatment consisted of chemotherapy with etoposide and cis‐platinum. The patient has remained well with no evidence of disease recurrence. The tumour markers remain normal.
Acute overdose of a new dopamine agonist, CV 205‐502
Authors: Tauveron Igor , Gesta Jean‐Michel , Jalenques Isabelle , Thiebiot Philippe 
Published: March 2008

SummaryCV 205‐502 is a new dopamine agonist used for hyperprolactinaemia. We report a case of acute overdose (one month treatment, i.e. 2.25 mg) in a 25‐year‐old male patient. Clinical symptoms were restricted to nausea and mild hypotension. Treatment consisting of ipeca cuanha, charcoal and intravenous fluids allowed a rapid, successful outcome. This case illustrates the particular features of CV 205‐502 intoxication when compared to other dopamine agonists, pointing out the tolerance of the drug which can be considered for wider indications and safer prescriptions.
Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence
Authors: Barclay Murray L. , Brownlie Bevan E. W. , Turner John G. , Wells J. Elisabeth 
Published: March 2008

SummaryOBJECTIVE Lithium is known to cause goitre and hypothyroidism, and has been associated less commonly with hyperthyroidism. We report a series of 14 patients with lithium associated thyrotoxicosis (LiAT), and have used epidemiological data to assess the association between long‐term lithium treatment and the development of thyrotoxicosis.DESIGN Information for this retrospective study was obtained from records of patients attending the thyroid clinic between 1973 and 1991. Statistical analysis of the association between long‐term lithium treatment and incidence of thyrotoxicosis was made using local thyrotoxicosis incidence figures and lithium prescription data. MEASUREMENTS Investigations included 99mTc pertechnetate thyroid scans, and blood analyses to measure serum T4, serum T3, free T4 index, and thyroid microsomal and thyroglobulin antibody litres.RESULTS During the 18‐year period there were 14 patients with LiAT. This number of cases of thyrotoxicosis occurring in patients on lithium was more than three times greater than that predicted from local thyrotoxicosis incidence rates (P< 0.05). Scintiscans were obtained for 13 patients: 8 had toxic diffuse goitre, 2 toxic multinodular goitre, 1 toxic uninodular goitre, and 2 had a lack of visualization consistent with ‘painless thyroiditis'. Nine patients received a course of carbimazole and 6 of these remain in remission. Six patients have received 131I therapy. Eight patients have become hypothyroid at follow‐up (5 post 131I, 1 following a course of carbimazole, and the 2 with ‘painless thyroiditis').CONCLUSIONS Statistical analysis has shown that long‐term lithium therapy is associated with an increased risk of thyrotoxicosis. LiAT is a heterogeneous condition with differing underlying thyroid pathologies and the mechanisms remain uncertain. The management of LiAT should initially be with antithyroid medication, and 131I therapy should be given only to patients who do not obtain long‐term remission.
The iodide perchlorate discharge test in women with previous post‐partum thyroiditis: relationship to sonographic appearance and thyroid function
Authors: Creagh F. M. , Parkes A. B. , Lee A. , Adams H. , Hall R. , Richards C. J. , Lazarus J. H. 
Published: March 2008

SummaryBACKGROUND Post‐partum thyroid disease occurs in 50% of anti‐thyroid peroxidase (TPO) antibody positive women (detected at 16 weeks' gestation) and is characterized by a transient episode of hyper, hypo or hyper‐hypo thyroidism. In approximately 20% of these women the hypothyroidism is permanent. However, the extent of long‐term thyroid dysfunction, possibly mediated by immune attack, in those anti‐TPO Ab + ve women who have had only transient or no thyroid dysfunction during the postpartum period is not clear.OBJECTIVE We have therefore studied the frequency of iodide organification defects by iodide perchlorate discharge testing, and of thyroid morphological abnormalities by ultrasound scanning in euthyroid women following their episode of post‐partum thyroiditis (PPT).DESIGN The study group comprised 17 women with previous PPT (PPT +ve) and 12 women who had positive anti‐TPO antibodies during pregnancy but who did not develop PPT (PPT‐ve). Women were studied 15‐47 months following their episode of PPT.RESULTS Iodide perchlorate discharge tests were positive (more than 10% discharge) in 7 (41 %) PPT + ve and 5 (42%) PPT‐ve subjects (P = NS). Morphological abnormalities on thyroid ultrasound were detected in 7 of 14 (50%) PPT + ve and 7 of 9 (77%) PPT‐ve subjects (P = NS). There was a strong association between abnormalities of iodide organification and morphology: of 11 subjects with positive iodide perchlorate discharge tests, 10 had abnormal (positive) ultrasound scans; of 12 subjects with negative iodide perchlorate discharge tests 8 had negative ultrasound scans (P= 0.013, Fisher's exact test).CONCLUSIONS Long‐term subtle defects of thyroid function and morphology are common in women with anti‐TPO antibodies in pregnancy, whether or not they develop postpartum thyroiditis. The clinical significance of these findings is unclear but a continuing thyroid pathological process is suggested.
Urinary excretion of pyridinium cross‐links in healthy women; the long‐term effects of menopause and oestrogen/progesterone therapy
Authors: Schlemmer A. , Hassager C. , Delmas P. D. , Christiansen C. 
Published: March 2008

SummaryOBJECTIVES We investigated the effect of the menopause when followed longitudinally for a decade to evaluate whether women with an increased bone loss continue to have elevated urinary excretion of pyridinium cross‐links later in menopause. Furthermore, we investigated the effect of oestrogen/progesterone therapy on the urinary excretion of pyridinium cross‐links.PARTICIPANTS In the cross‐sectional study: 18 healthy premenopausal, 142 healthy post‐menopausal women and 41 osteopenic post‐menopausal women. In the longitudinal study: 45 healthy post‐menopausal women followed up for 7‐10 years after the menopause; these women were further divided into two equal groups, according to their loss of forearm bone mineral content over 2 years.In the oestradiol/progesterone double‐blind, placebo‐controlled 2‐year trial: early post‐menopausal women were given either hormone replacement therapy (n = 38) or placebo (n= 16).MEASUREMENTS The urinary excretion of pyridinoline/ creatinine (Pyr/Cr) and urinary deoxypyridinoline/creatinine (D‐Pyr/Cr), two new markers of bone resorption.RESULTS Pyr/Cr and D‐Pyr/Cr increased significantly after the menopause (Pyr/Cr, 77%; D‐Pyr/Cr, 98%, P < 0.001). Hormone replacement therapy reversed this increase towards premenopausal levels. Both pyridinium cross‐links remained fairly constant during the first decade of the menopause, when measured in the longitudinal study.When the women were divided according to loss in forearm BMC., those with a loss greater than 3‐5%/2 years had significantly higher levels of pyridinium cross‐links (P<0.05‐0 01).Furthermore, both Pyr/Cr and D‐Pyr/Cr were significantly higher in elderly osteopenic women (aged 68‐72 years) than in age‐matched non‐osteopenic women (P<0.01‐0.001).CONCLUSIONS Both Pyr/Cr and D‐Pyr/Cr, two new markers of bone resorption, increased significantly at the time of the menopause, thereafter remaining fairly constant during the first post‐menopausal decade. Women with increased bone loss continue to have elevated urinary excretion of pyridinium cross‐links during the first decade of the menopause. This post‐menopausal change is reversed by hormone replacement therapy to the premenopausal level.
Interaction of salbutamol with pyridostigmine and arginine on both basal and GHRH‐stimulated GH secretion in humans
Authors: Ghigo E. , Arvat E. , Gianotti L. , Ramunni J. , Maccario M. , Camanni F. 
Published: March 2008

SummaryOBJECTIVE It is well known that acetylcholine and arginine stimulate GH secretion while activation of β‐adrenergic receptors inhibits GH secretion in man. We aimed therefore to ascertain whether or not the inhibitory influence of β‐adrenergic receptors on GH secretion would over‐ride the stimulatory one of acetylcholine and arginine.DESIGN We studied the interaction of salbutamol, a β2‐adrenergic agonist (SAL, 0.08 mg/kg orally) with pyridostigmine, a cholinesterase inhibitor (PD, 120 mg orally), or arginine (0.5 g/kg i.v.) on both basal and GHRH (1 μg/kg i.v.)‐stimulated GH secretion.SUBJECTS Fourteen healthy male volunteers, aged 20–35 years, were studied.MEASUREMENTS Serum GH was measured in duplicate by immunoradiometric assay.RESULTS In study A, SAL inhibited the GH response both to GHRH (P < 0.01) and ARG(P<0.002). ARG enhanced the GHRH‐induced GH rise (P<0.01) but its effect was abolished (P<0.02) by SAL pretreatment. In study B, SAL inhibited the GH response both to GHRH (P<0.01) and PD (P< 0.02). PD enhanced the GH response to GHRH (P < 0.01) but its effect was abolished (P<0.05) by SAL pretreatment. In both studies, the GH response to GHRH alone was similar to that to the neurohormone when combined with ARG + SAL or PD + SAL.CONCLUSION Our results show that β2‐adrenergic activation by salbutamol is able to inhibit not only the GH rise induced by GHRH, arginine and pyridostigmine, but even the potentiating effect of both arginine and pyridostigmine on the GH response to GHRH. They indicate that catecholamines, acetylcholine and arginine play a major role in GH secretion having opposite influences aimed to balance the function of the hypothalamus‐GH‐IGF‐l axis in man.
Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre
Authors: Chiovato Luca , Santini Ferruccio , Vitti Paolo , Bendinelli Giovanna , Pinchera Aldo 
Published: March 2008

SummaryA patient with toxic nodular goitre is described in whom radioiodine (131I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse 131I uptake by the gland. A second administration of 131I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH‐receptor antibody and thyroid stimulating antibody were undetectable before 131I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of 131I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH‐receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH‐receptor, thus turning a toxic nodular goitre into Graves' disease.