ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02136.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 tre

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02137.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 phys

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02138.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim of this study was to refine the biochemical definition of disease activity in acromegaly by comparing serum growth hormone (GH) measurements during a 10‐hour day profile with serum GH values during an oral glucose tolerance test.DESIGN Using plasma insulin‐like growth factor‐1 (IGF‐1) levels as a measure of disease activity, serum GH data from a day profile and from an oral glucose tolerance test were compared.PATIENTS Thirty‐five acromegalic patients were studied, 13 of whom had serum GH measured during a day profile and 22 during an oral glucose tolerance test. In addition, basal plasma IGF‐1 levels were estimated in all acromegalic patients, and in 24 normal subjects.MEASUREMENTS Following acid‐ethanol extraction of the plasma samples, IGF‐1 levels were measured by radioimmunoassay using a polyclonal antibody. In a day profile, six to eight blood samples for serum GH estimation were taken at hourly intervals during the day; during an oral glucose tolerance test samples for serum GH estimation were taken in the fasting state and every 30 minutes for 2 hours and measured by a two‐site IRMA for GH. RESULTS Ninety‐four per cent of acromegalic patients with raised plasma IGF‐1 levels had serum GH concentrations40 mU/l but maintaining a linear relationship with serum GH levels<20 mU/l.CONCLUSIONS A highly significant correlation exists between plasma IGF‐1 levels and various parameters of serum GH levels in acromegalic patients. Hormonal assessment of disease activity in acromegaly is more accurately reflected by the serum GH concentration during an oral glucose tolerance test rather than by the serum GH level during a day profile. Normalization of plasma IGF‐1 levels is rarely achieved unless the mea

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02139.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 PGE2with 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 PGE2production 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

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02140.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE This study was designed to compare the clinical and biochemical features of patients with Cushing's disease without pathological evidence of pituitary adenoma (n= 11) to those in whom a pituitary ACTH adenoma was documented (n= 11).DESIGN The clinical and biochemical features of 11 patients with Cushing's disease without pathological evidence of pituitary adenomas were compared to 11 subjects with ACTH‐secreting adenomas. The patients underwent transsphenoidal microsurgery between 1979 and 1989. During surgery, when an adenoma was not visualized, a partial hypophysectomy of the central mucoid wedge was performed.MEASUREMENTS Cushing's disease was established by the clinical features of hypercortisolism and the high levels of 24‐hour free urinary Cortisol with no suppression inresponseto low, but with suppression in response to high, doses of dexamethasone. Basal and post TRH‐GnRH plasma prolactin, FSH and LH levels were assessed in each patient before transsphenoidal microsurgery.RESULTS Similar results were observed in patients with and without ACTH‐secreting adenomas regarding cure rate, and free urinary Cortisol levels both basal and after 2 days of dexamethasone, 8 mg daily. After surgery, plasma Cortisol levels in cured patients were lower in subjects with ACTH‐secreting adenomas than in those without pituitary tumours (P< 0.05). Areas under the curve of PRL (P<0.002) and LH (P<0.04) were significantly higher in patients without pituitary adenoma after TRH‐GnRH administration. Compared to controls, the peak prolactin level after TRH‐GnRH administration was higher in patients without pituitary adenoma (P<0005) and lower in those with ACTH adenoma (P<0.05). Furthermore, a peak prolactin level equal to or greater than 1410 mU/l during the TRH‐GnRH test was found in 11/11 patients without ACTH adenoma and 3/11 patients in the other group (P<0 001), while the CT‐scan findings were suggestive of pituitary adenoma in six patients of each group. CONCLUSION This study suggests that patients with Cushing's disease without pituitary adenomas can be distinguished from those with ACTH‐secreting adenomas by their high prolactin levels after TRH

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02141.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVES We compared the responses of the stress hormones, Cortisol, ACTH, vasopressin (AVP), corticotrophin releasing hormone (CRH) and catecholamines to elective conventional and laparoscopic cholecystectomy.DESIGN A right upper quadrant transverse incision was used for conventional cholecystectomy, and four 1–2‐cm incisions for the laparoscopic procedure (for insertion of surgical instruments, diathermy, fibreoptic telescope and light source, and carbon dioxide insufflation). Blood was sampled immediately prior to premedication (temazepam), after induction of anaesthesia (fentanyl and thiopentone) and at 10‐minute intervals until the end of the procedure (N2O maintenance, vecuronium relaxation). A blood sample was taken after reversal, and then at 10‐minute intervals for 50 minutes. Plasma sodium and blood pressure were measured at similar intervals. Results are expressed as mean ± standard error.PATIENTS Twelve patients were studied (six in each group).MEASUREMENTS Peptide hormones were measured by radioimmunoassay, Cortisol by ELISA and catecholamines by HPLC.RESULTS The mean premedication hormone values for the conventional and laparoscopic procedures did not increase significantly after induction of anaesthesia. Within 10 minutes of the first incision, however, there was a marked concordant rise in mean plasma ACTH and AVP levels for both procedures (conventional: ACTH, from a premedication value of 10 2 ± 1 7 to 80 1 ± 14 3 pmol/l, AVP from 1 2 ± 0 4 to 117 ± 4 24 pmol/l,P<0 01 for both hormones; laparoscopic: ACTH from 5 8 ± 26 to 551 ± 260 pmol/l, AVP from 1 6 ± 0 11 to 49 2 ± 27 09 pmol/l). At the end of both types of operation mean levels of ACTH and AVP were still elevated, although the ACTH: AVP ratio had increased. Greater variability in ACTH and AVP responses was seen in the laparoscopic than in the conventional procedure, three patients showing a relatively small response to surgery. Total secretion of ACTH during both types of surgery was not significantly different but the total secretion of AVP was significantly less both during (P<0 05), and after (P<0 01) laparoscopic surgery. For both procedures, the timing of AVP and ACTH peaks was significantly related (P<0 002). A small but significant rise in CRH was observed 30 minutes after the start of surgery for both proceduresP<005). The timing of CRH and ACTH peaks was unrelated. The maximum mean plasma Cortisol level for the conventional procedure (1268 ± 147 nmol/l) was reached 20 minutes after reversal of anaesthesia and remained at this level until the end of sampling. The Cortisol response was comparable during the laparoscopic procedure but was beginning to fall at 60 minutes post‐operatively. Plasma adrenaline responses to the two types of surgery were not significantly different, but the plasma total noradrenaline response to laparoscopic surgery as indicated by the response area during the first 20 minutes was significantly increased (P<0 02). Plasma sodium, renin activity and initial systolic blood pressure fall were not significantly different during the two procedures.CONCLUSIONS For both procedures, the peak of ACTH secretion after incision is likely to be AVP dependent, and the timing of peak levels of these two hormones was significantly related. Subsequent ACTH secretion may be the result of an interaction between AVP and CRH. Laparoscopic cholecystectomy results in a smaller AVP rise than does the conventional procedure, and plasma AVP falls more rapidly post‐operatively. During the period of observation, ACTH, CRH, Cortisol and adrenaline responses were not significantly lessened by the laparoscopic approach, but there was a significant increase in the noradrenaline response. Stress hormone monitoring may assist further improvements

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02142.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE Recent reports have suggested that hypogonadotrophic hypogonadism in men with genetic haemochromatosis can be reversed by aggressive venesection therapy. We have studied prospectively men with this complication of haemochromatosis in order to document the frequency and completeness of recovery from hypogonadism.PATIENTS AND DESIGN Six men with symptomatic hypogonadotrophic hypogonadism and genetic haemochromatosis were studied before beginning venesection therapy and again after depletion of body iron stores.MEASUREMENT Symptoms of hypogonadism, serum gonadotrophins and serum total and free testosterone concentrations.RESULTS Five men aged 47–66 showed no symptomatic improvement and no change in serum gonadotrophin or testosterone concentrations. The symptoms of one man, aged 33, resolved completely after venesection and this was accompanied by increases in serum LH and FSH. Serum total and free testosterone concentrations increased fourfold, but remained subnormal.CONCLUSION Only one partial recovery from hypogonadotrophic hypogonadism was seen and this was in the youngest subject. In reviewing the other documented cases of reversal it would appear that the age at diagnosis is critical and there are no proven cases of reversal of hypogonadotrophic hypogonadism in men over the age of 40 at the start of venesection therap

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02143.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The relationship between insulin resistance and hyperandrogenism led us to study insulin resistance in polycystic ovary syndrome (PCOS) in order to determine its prevalence and pathogenesis. DESIGN Blood samples were taken on the 8th day after menses commenced.PATIENTS Sixty‐one women with PCOS, 30 with normal weight (BMK25 kg/m2) (group 1) and 31 with obesity (BMI<26 kg/m2) (group 2) were studied. They were divided also according to LH level: group A, low or normal LH (n==23) and group B, high LH (n= 38). Twenty lean control women and 16 obese control women were studied.MEASUREMENTS Serum LH, testosterone, free testosterone, dehydroepiandrosterone, sex‐hormone binding globulin, androstenedione, and fasting insulin were measured. Insulin sensitivity was explored by the insulin tolerance test (ITT). ITT was performed by bolus i.v. insulin of 0 1 IU/kg. Blood glucose was measured before (– 5, 0) and after injection (3, 5, 7, 10, 15 minutes). Insulin sensitivity was given by the ratio of glycaemic variation to initial blood glucose (AG/G index).RESULTS ΔG/G was correlated with other insulin resistance parameters, particularly fasting insulinr=–0.40,P<0.01. The PCOS groups had the following insulin resistances (mean ± SEM) compared to matched groups: ΔG/G lean PCOSvslead controls: 0.45 ± 0.02vs0.61 ± 0.01,P<0.001; ΔG/G obese PCOSvsobese controls: 0.32 ± 0.02vs0.40 ± 0.01,P<0.02. Insulin resistance was higher in group A than in group B: ΔG/G 0 29 ± 002vs0 45 ± 0 02,P<0.001. The prevalence of insulin resistance was 63% in lean PCOS and 51% in obese PCOS. Positive correlations between AG/G index and LH were found in group 1 and 2, respectivelyr= 0.45,P<0.01 andr= 0.55,P<0.01.CONCLUSION PCOS was associated with a significant decrease of insulin sensitivity, independent of obesity. The correlation between LH and insulin sensitivity suggests a complement

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02144.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We determined whether a progestogen given alone to post‐menopausal women may prevent bone loss.STUDY DESIGN Thirty‐five early post‐menopausal women who had not received any form of treatment to prevent bone loss were randomly assigned to a 2‐year regimen of 500μg/day of a gestagen derived from 19‐norprogester‐one (Promegestone) or a placebo for 21 days out of a 28‐day treatment cycle. Bone mineral density of the spine was measured by dual photon absorptiometry.RESULTS After 2 years of treatment bone mineral density decreased significantly in the placebo group by a mean of 4.5%. In the gestagen group, the rate of bone change was significantly lower as compared to the placebo group (‐1.3%± 1.2% vs −4.5%± 2% (mean ± SEM),P< 0.05). There were no changes in the biochemical bone turnover parameters in the placebo group but in the gestagen group a significant decrease was observed in the urinary calcium excretion after 2 years.CONCLUSION The results suggest that a gestagen with no androgenic action can partly counteract early post

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb02145.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY