bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of a pure anti‐androgen (flutamide) on LH, FSH, androgens and clinical status in idiopathic hirsutism
Authors: Couzinet Beatrice , Pholsena Maryse , Young Jacques , Schaison Gilbert 
Published: March 2008

SummaryOBJECTIVES We assessed in women the effects of androgen suppression on gonadotrophin secretion and the therapeutic efficacy of the pure anti‐androgen flutamide (2‐methyl‐N‐[4‐nitro‐3‐(trifluoromethyl)phenyl]‐propanamide).DESIGN AND SUBJECTS Ten women, aged 28‐35 years, using an intrauterine device for contraception, were selected for this study. All women had idiopathic hirsutism with or without acne and seborrhoea. Flutamide was administered orally in a dose of 250 mg twice daily for 1 year. Basal body temperature was recorded and pelvic ultrasonography performed before and every 3 months during treatment. LH pulse frequency and amplitude (Cluster analysis) and basal and GnRH‐stimulated plasma LH and FSH levels were determined on day 5 of the cycle prior to flutamide treatment, and after 6 and 12 months of therapy. Plasma total testosterone (T), non‐SHBG bound T, androstenedione (A), dehydroepiandrosterone sulphate (DHEAS), androstanediol glucuronide (3α‐diol G) and sex hormone binding globulin (SHBG) levels were measured before and every 3 months during therapy, on day 5 of the cycle. Plasma oestradiol and progesterone levels were determined on day 22 of the studied cycles.RESULTS Disappearance of acne and seborrhoea occurred after 2 months with a marked improvement of hirsutism at 6 months. At 12 months, hirsutism had disappeared with a Ferriman and Galiwey score < 7. No adverse side‐effects, apart from transient diarrhoea in two patients, were reported with this flutamide dose. None of the patients had any disturbance of menstrual cycles which remained ovulatory. The pure anti‐androgen flutamide induced no significant change in LH pulsatile profile, nor in LH and FSH responsiveness to GnRH. Plasma concentrations of steroids were not altered. Plasma SHBG and 3al‐diol G levels did not change during flutamide treatment.CONCLUSION Flutamide, which interacts only with the androgen receptor, is effective for hirsutism, acne and seborrhoea, and does not disturb menstrual cyclicity or ovulation. It may represent a treatment of choice for essential hirsutism in women using safe contraceptive methods.
Deficient inactivation of cortisol by 11β‐hydroxysteroid dehydrogenase in essential hypertension
Authors: Walker Brian R. , Stewart Paul M. , Shackleton Cedric H. L. , Padfield Paul L. , Edwards Christopher R. W. 
Published: March 2008

SummaryOBJECTIVE 11β‐Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from Cortisol by converting Cortisol to inactive cortisone. 11β‐Dehydrogenase deficiency, either congenital or after inhibition by liquorice and carbenoxolone, results in cortisol‐dependent mineralocorticoid excess and hypertension. We tested the hypothesis that the same mechanism occurs in some patients with essential hypertension.DESIGN/PATIENTS Twenty patients with essential hypertension were compared with 19 matched healthy controls.MEASUREMENTS 11β‐Hydroxysteroid dehydrogenase activity was assessed by the half‐life of 11α‐3H‐cortisol, and by the ratios of Cortisol to cortisone in plasma and of their metabolites in urine. Renal mineralocorticoid receptor activation was assessed by plasma potassium, renin activity and aldosterone.RESULTS Half‐lives of 11α‐3H‐cortisol were prolonged in a subgroup of hypertensives (mean ± SE 53.2 ± 3.6 min in hypertensivesvs42.3 ± 2.3 in controls,P<0.05; seven of the 20 hypertensives had half‐lives exceeding 2 SD of controls). Ratios of Cortisol to cortisone in plasma and of their metabolites in urine were not different. 11α‐3H‐Cortisol half‐lives correlated with blood pressure but not with indices of renal mineralocorticoid receptor activation.CONCLUSIONS 11β‐Dehydrogenase is defective in a proportion of patients with essential hypertension. The normal ratios of Cortisol to cortisone in plasma and of their metabolites in urine, also seen after carbenoxolone administration, suggest that 11β‐reductase conversion of cortisone to Cortisol is also defective. Unlike other syndromes of 11β‐dehydrogenase deficiency, the defect was not associated with mineralocorticoid excess. We suggest that it may cause hypertension by increasing exposure of vascular steroid receptors to Cortisol.
The combined use of intravenous and oral calcium for the treatment of vitamin D dependent rickets type II (VDDRII)
Authors: Al‐Aqeel Aida , Ozand Pinar , Sobki Samia , Sewairi Wafa , Marx Stephen 
Published: March 2008

SummaryOBJECTIVE Some patients with rickets are resistant to vitamin D and its analogues; we therefore assessed whether or not normal mineralization could be achieved in the absence of an intact 1,25(OH)2D3 receptor‐effector system, by the use of intravenous high dose calcium infusion, followed by high dose oral calcium.DESIGN We studied two patients with vitamin D dependent rickets type II and with absent responses to either high dose calcitriol or to oral calcium alone. Daily infusions equivalent to up to 14 g elemental calcium supplemented with oral phosphate were given for a period of 3 5 months for the elder sister and 2 months in the younger brother. Both patients were then treated by weekly calcium infusions for 5 months, followed by maintenance on oral calcium equivalent to up to 6 g elemental calcium per day.PATIENTS Two siblings of consanguineous parents, a girl aged 28 months and a boy aged 10 months with vitamin D dependent rickets type II.MEASUREMENTS Measurements of serum and urine calcium, phosphate and serum alkaline phosphatase were obtained before, during and after the calcium infusions.Twenty‐four‐hour urinary minerals, electrolytes, creatinine clearance, serum PTH and vitamin D metabolites were measured prior to calcium infusion, then repeated at 2‐monthly intervals. Glomerular filtration rate, kidney ultrasound and CT scan were done at 6‐monthly intervals. A scalp biopsy was done at the end of i.v. calcium treatment.RESULTS The daily infusions of calcium supplemented with oral phosphate resulted in biochemical responses with normalization of calcium and phosphate in 3‐5 days, and of alkaline phosphatase and PTH in 15‐2 months. Radiological evidence of healing was seen in 42 days. A total of 3 5 months of daily calcium infusion in the elder sister and 2 months in the younger brother resulted in complete healing biochemically and radiologically, with improvement in height. The patients are under current follow‐up, with no evidence of nephrocalcinosis or deterioration of glomerular filtration rate.CONCLUSION

The use of intravenous high dose calcium infusions followed by high dose oral calcium is an effective method of treatment of vitamin D dependent rickets type II.
The treatment was more effective since it was started early in the course of the disease and led to early healing and better growth with prevention of bone deformities.
Early treatment may also lead to improvement in alopecia, the mechanism for which needs to be elucidated.
Deoxycorticosterone, 11 β‐hydroxylase and the adrenal cortex
Authors: Spoudeas Helen A. , Slater J. D. H. , Rumsby Gillian , Honour John W. , Brook Charles G. D. 
Published: March 2008

SummaryWe report a child in whom DOC excess secondary to congenital adrenal hyperplasia (CAH, 11β‐hydroxylase deficiency) caused malignant hypertension. Clinical and metabolic control could be achieved only by replacement of both glucocorticoid and mineralocorticoid, thus confirming in clinical practice the hypothesis that DOC is produced from both the zonae fasciculata and glomeru‐losa of the adrenal cortex under the independent control of the ACTH and renin‐angiotensin systems respectively.
Thyrotoxicosis increases right to left shunt in congenital cyanotic heart disease
Authors: Orme S. M. , Sebastian J. P. , Page M. D. , Cowan C. , Belchetz P. E. 
Published: March 2008

SummaryWe wish to report two cases of congenital cyanotic heart disease in whom coexisting thyrotoxicosis increased the right to left shunt. We review the literature on the cardiac and respiratory effects of thyroid hormone to try to explain this phenomenon. Two patients, one with Fallot's tetralogy (diagnosed at 68 yars of age), the other with a ventricular septal defect, developed thyrotoxicosis which resulted in a dramatic but reversible deterioration in their cardiac condition.We conclude that thyrotoxicosis increases right to left shunt in congenital cyanotic heart disease. This effect is profound but reversible. We suggest that when an unexplained rapid deterioration occurs in patients with congenital cyanotic heart disease, thyrotoxicosis should be excluded.
The long‐term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas
Authors: Brada M. , Rajan B. , Traish D. , Ashley S. , Holmes‐Sellors P. J. , Nussey S. , Uttley D. 
Published: March 2008

SummaryOBJECTIVES We assessed the long‐term efficacy and toxicity of conservative surgery and radiotherapy in the control of pituitary adenomas.DESIGN Retrospective study of patients treated at the Royal Marsden Hospital.PATIENTS Four hundred and eleven patients with pituitary adenomas treated with conventional external beam radiotherapy at the Royal Marsden Hospital between 1962 and 1986. Two hundred and fifty‐two patients had clinically non‐functioning pituitary adenomas, 131 had hormone secreting tumours and in 28 patients the secretory status was not known. Three hundred and thirty‐eight patients had surgical intervention of whom only 11 had complete tumour excision. All patients received conventional fractionated external beam radiotherapy to a dose of 45–50Gy in 25–30 fractions.MEASUREMENTS Actuarial progression free survival and overall survival and assessment of toxicity, particularly in terms of vision, requirement for hormone replacement therapy and incidence of second tumours.RESULTS The actuarial progression free survival was 94% at 10 years and 88% at 20 years for all patients and 97% at 10 years and 92% at 20 years for patients with clinically non‐functioning adenomas. Only secretory status was an independent prognostic factor for disease control. The 10 and 20‐year survivals for all patients were 77 and 58% respectively. When compared with the normal population the relative risk of death was 1 76 (P<0 001) and no prognostic factors for survival were identified. The morbidity of radiotherapy was low. Visual deterioration, assumed to be radiation induced, occurred in 1–5% of patients and the risk of second brain tumour was 1.9% at 20 years. Fifty per cent of patients received hormone replacement therapy by 19 years.CONCLUSION Conventional external beam radiotherapy as described here combined with conservative surgery is safe and effective in the control of pitutary adenomas. These results should form a baseline for comparison with new treatment strategies.
Pituitary responsiveness after administration of a GnRH agonist depot formulation: Decapeptyl CR
Authors: Broekmans F. J. , Bernardus R. E. , Broeders A. , Berkhout G. , Schoemaker J. 
Published: March 2008

SummaryOBJECTIVE This study was focused on the pattern of LH release from the pituitary during the initial response to high dose GnRH agonist administration. Secondly, the pattern of LH release and the pituitary responsiveness to physiological and pharmacological stimulation during long‐term pituitary suppression by a high dose GnRH agonist was studied. In addition, the relation between serum agonist levels and pituitary function and responsiveness was investigated.DESIGN oTrp'GnRH in microcapsules (Decapeptyl CR) was administered i.m. to 12 women on the third day of the cycle. High‐rate blood sampling was carried out during the first 48 hours after the injection. Secondly, high‐rate blood sampling for 6 hours and a GnRH challenge were performed before and weekly after administration, from week 4 till week 9. All samples were assayed for LH and FSH. LH patterns were analysed by applying a computerized pulse detection program. In the second or third week an oestradiol benzoate test was performed. Finally, trip‐torelin levels were measured before and weekly after administration.PATIENTS Twelve patients, suffering from tubal infertility and recruited from the waiting list for in‐vitro fertilization/ embryo transfer (IVF/ET) participated in the study.RESULTS During the first 48‐hour period, LH and FSH levels demonstrated a rapid rise to peak values after 4 hours, subsequently declining to nearly normal levels. E2 rose to peak values at 12 hours and returned to the follicular range thereafter. LH pulse patterns showed a rapid increase in pulse intervals leading to a near absence of LH pulses at the end of the 48‐hour period.From the fourth till the seventh week after agonist administration, LH pulse patterns showed a markedly increased pulse interval, decreased pulse amplitude, and a severely decreased mean LH level. In the same period, LH responses to GnRH were severely blunted or absent. Restoration of the pre‐injection LH pulse pattern and the LH response to GnRH was observed during the eighth and ninth week. Oestradiol benzoate challenges showed an E2 rise to preovulatory levels in response to the injections. However, no changes were observed in LH and FSH concentrations. Triptorelin levels showed a peak within 48 hours and gradual decline towards pretreatment values in week eight.conclusions It is concluded from the study, that after administration of triptorelin depot in the early follicular phase, desensitization of the pituitary starts to develop within 24 hours. Pituitary responsiveness is completely absent in the second week and continues to exist until the eighth week after injection, when the agonist has disappeared from the circulation. These findings suggest profound alterations in GnRH receptor availability and post‐receptor pathways, that prevent the pituitary from responding to physiological stimuli.
Pathophysiology of transient cranial diabetes insipidus during pregnancy
Authors: Williams David J. , Metcalfe Karl A. , Skingle Linda , Stock Antony I. , Beedham Trevor , Monson John P. 
Published: March 2008

SummaryOBJECTIVE We investigated the possible mechanisms underlying transient cranial diabetes insipidus during pregnancy.DESIGN AND PATIENTS A woman who developed clinical diabetes insipidus during the third trimester of pregnancy was studied through a total of three pregnancies and postpartumMEASUREMENTS Plasma AVP, urine and plasma osmolality, urine volume and specific gravity were measured during water deprivation tests and hypertonic saline infusion. Plasma and urine osmolality were measured after subcutaneous injection of AVP. The water deprivation and AVP test were repeated after proven inhibition of urinary PGE2 with aspirin. Serum vasopressinase activity was measured during one of the pregnancies affected with diabetes insipidus and compared with that obtained between 26 and 38 weeks from 13 normal pregnancies.RESULTS The patient was found to have cranial diabetes insipidus which responded to low dose intranasal 1‐desamino‐8‐D‐arginine vasopressin. Inhibition of PGE2 with aspirin did not enhance urine concentrating ability or the response to a test dose of subcutaneous AVP. Plasma levels of vasopressinase remained within the physiological range for normal pregnancy.CONCLUSIONS These studies indicate that subclinical cranial diabetes insipidus may be unmasked in late pregnancy. This effect is not related to AVP resistance resulting from PGE2 production or excessive vasopressinase activity, but may be due to a combination of physiological vasopressinase secretion with reduced AVP secretory capacity and reduction in the thirst threshold that accompanies normal pregnancy.We relate these findings to a previously described group of women with transient diabetes insipidus during pregnancy who had impaired liver function
Direct inhibition of ovarian steroidogenesis by Cortisol and the modulatory role of 11β‐hydroxysteroid dehydrogenase
Authors: Michael A. E. , Pester L. A. , Curtis P. , Shaw R. W. , Edwards C. R. W. , Cooke B. A. 
Published: March 2008

SummaryOBJECTIVE The association of adrenal hyperactivity with ovarian dysfunction may involve direct inhibition of ovarian steroidogenesis by glucocorticoids. Therefore, the objectives of this study were to investigate the direct effects of Cortisol on luteinizing hormone (LH) action in human granulosa‐lutein cells and the modulation of this interaction by ovarian 11β‐Miydroxysteroid dehydrogenase (11βHSD).DESIGN AND PATIENTS Effects were investigated in cultured human granulosa‐lutein cells isolated from the follicular aspirates of 14 patients undergoing oocyte collection for in‐vitro fertilization and embryo transfer.MEASUREMENTS Pregnenolone production and 3H‐Cortisol oxidation to 3H‐cortisone (11βHSD activity) by cultured cells were measured.RESULTS In cells from nine (of 14) patients, Cortisol inhibited LH‐stimulated steroidogenesis in a concentration dependent manner with an ID50 of 1250 ±SEM 377 nmol/t. In these cultures, the 11/JHSD activities were high (133±SEM 23 pmol/mg protein/4h) and inhibition of the enzyme with carbenoxolone potentiated the action of Cortisol. Conversely, cells from the remaining five patients lacked detectable 11β HSD activity and exhibited an increased sensitivity to the inhibitory action of Cortisol (ID50= 158 ± SEM 41 nmol/l in the absence of carbenoxolone).CONCLUSIONS Cortisol acts directly in human granulosalutein cells to inhibit the support of steroidogenesis by LH and this interaction is modulated by ovarian 11βHSD in the majority of patients.
Evidence for a single gene effect causing polycystic ovaries and male pattern baldness
Authors: Carey A. H. , Chan K. L. , Short F. , White D. , Williamson R. , Franks S. 
Published: March 2008

SummaryOBJECTIVE Polycystic ovary syndrome is one of the most common endocrine disorders but its aetiology remains unknown. It is highly prevalent within families, suggesting a genetic basic for the syndrome, but the mode of inheritance is unclear. The purpose of this study was to determine the mode of inheritance of polycystic ovary syndrome, within the families of affected individuals, by classic segregation analysis.DESIGN All first degree relatives of affected individuals were screened for the presence or absence of polycystic ovaries in post‐menarchal‐premenopausal women and early onset male pattern baldness (MPB) in the males. In extended pedigrees, assignment of affected status in postmenopausal women was made by consideration of the clinical history alone.PATIENTS Fourteen women (probands), presenting with a variety of clinical symptoms, were identified sequentially as having polycystic ovaries (PCO) by ultrasound scan. They were examined in detail to determine their family structure, clinical and endocrine status. Ten families were found to have sufficient members for further study.MEASUREMENTS All family members had their body mass index calculated, their degree of hirsutism assessed using the Ferriman and Gallwey score and serum levels of gonadotrophins (FSH and LH), testosterone, prolactin and 17α‐hydroxyprogesterone measured by radioimmunoassay. A careful reproductive history was taken for each woman and any menstrual disturbance was noted. Obese probands had their glucose and insulin response to a standard 75‐g oral glucose tolerance test determined. Each male family member was also assessed for the degree and time of onset of balding.RESULTS First degree female relatives of affected individuals had a 51 % chance of being affected. Early onset male pattern baldness (MPB) was found to be an accurate phenotype for obligate male carriers. Each family showed autosomal dominant inheritance for PCO with greater than 90% penetrance.CONCLUSIONS We postulate that PCO and male pattern baldness are caused by alleles of the same gene which affect androgen production or action. The different frequencies of PCO and male pattern baldness arise from differing thresholds for phenotypic expression in females and males respectively. The modifying effects of other genes is the most likely explanation of the somewhat variable phenotype.
Prospective study of the hypothalamic‐pituitary axis in thalassaemic patients who developed secondary amenorrhoea
Authors: Chatterjee R. , Katz M. , Cox T. F. , Porter J. B. 
Published: March 2008

SummaryOBJECTIVE We aimed to prospectively evaluate during 10 years the GnRH‐gonadotrophin secretory dynamics in a cohort of 15 menstruating girls with beta‐thalassaemia major to determine whether they sustained progressive damage to this axis.DESIGN Patients were characterized by 12‐hour gonadotropin profiles (by sampling blood at 15‐minute intervals) and assessment of gonadotrophin responses to 100 μ g GnRH bolus (by sampling blood at 20‐minute intervals for 1 hour and at 2 hours) sequentially during the follicular and luteal phases of their menstrual cycles, 12–14 months and 5–6 years after the onset of secondary amenorrhoea.SUBJECTS We studied 15 post‐menarcheal thalassaemic girls and five age‐matched control subjects who were the healthy siblings of the patients.MEASUREMENTS FSH and LH assays were determined using commercial RIA systems and double antibody techniques. Pulse detection used the Pulsar technique of Merriam and Wachter.RESULTS We demonstrated that during their amenorrhoeic period, all thalassaemic patients had gonadotrophin pulse abnormalities and low‐normal GnRH‐stimulated gonadotrophin levels indicating that they had GnRH‐gonadotrophin secretory insufficiency. During the subsequent 10 years there was progressive deterioration of hypothalamic‐pituitary function in all patients; 66% became apulsatile and all had marked reduction in their GnRH‐stimulated gonadotrophin levels.CONCLUSIONS Our investigation suggests that thalassaemic patients with secondary amenorrhoea had severe and progressive damage to their hypothalamic‐pituitary axes despite intensive chelation therapy.
Adrenocorticotrophin and Cortisol secretion in children after low dose cranial irradiation
Authors: Crowne E. C. , Wallace W. H. B. , Gibson S. , Moore C. M. , White A. , Shalet S. M. 
Published: March 2008

SummaryOBJECTIVE We investigated the effect of low dose cranial irradiation (18–24 Gy) on spontaneous ACTH and Cortisol secretion in children.DESIGN We analysed 24‐hour plasma ACTH and Cortisol profiles sampled at 20‐minute intervals.PATIENTS Twenty long‐term survivors of acute lymphoblastic leukaemia were studied and results compared with those in 14 normal children.MEASUREMENTS ACTH and Cortisol profiles were analysed by Fourier transformation and spectral analysis of stationarized data, autocorrelation and coherency analysis.RESULTS The normal circadian rhythms of ACTH and Cortisol were preserved in the children after cranial irradiation. The median 0900 h and midnight values were 1 50 (0 8–6 4)pmol/l and 1 0(0 6–3–7)pmol/l respectively for ACTH and 282(48–1913) nmol/l and 57 5(44–637)nmol/l respectively for Cortisol, and were not significantly different from those in the normal group. Fourier transformation revealed dominant periodicities for ACTH at 0–7–11 h, equivalent to 22–34 ACTH secretory bursts per 24 hours, and for Cortisol at 0 7–11 h and 2–4 8 h. Similar results were found in the normal group.Coherency analysis indicated a significant shared periodicity of 0 7–1 2 h in nine children, corresponding to 20–34 related secretory bursts in 24 hours for ACTH and Cortisol. After pooling the coherency spectra in the cranially irradiated group, comparison with the pooled data from the normal group revealed no significant difference between the two groups in the relationship between the two hormones.CONCLUSION No significant disruption of spontaneous ACTH or Cortisol secretion, either in the amount or pattern of hormones secreted, was found in children after low dose cranial irradiation (18–24 Gy).