ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.680502.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE We have determined the frequency of specific mutations in theRETproto‐oncogene in sporadic medullary thyroid carcinomas (MTCs) and correlated the presence or absence of a codon 918 mutation with the clinical characteristics of these tumours.DESIGN Thirty paraffin‐embedded sporadic MTCs and two frozen MTCs were collected for analysis of specific mutations in theRETproto‐oncogene in codons 609, 611, 618 and 620 (exon 10); 630 and 634 (exon 11); 768 (exon 13); 883 (exon 15) and 918 (exon 16). A novel primer was designed which introduced a restriction site forRsaI in the presence of the specific codon 918 mutation (ATG → ACG) in these tumour samples. A ‘clinical‐genetic’ correlation was performed comparing the presence or absence of the codon 918 mutation with the following clinical characteristics: age at diagnosis, tumour size, presence or absence of metastases, MTC related morbidity, and base line calcitonin levels at diagnosis or most recent follow‐up.PATIENTS Patients were classified as having sporadic MTC if there was no family history of C‐cell hyperplasia, MTC, phaeochromocytoma or parathyroid disease. Retrospective review of patient records enabled complete clinical data to be obtained in 28 of 32 patients.MEASUREMENTS Base line calcitonin levels were measured by radioimmunoassay or calcitonin enzyme linked immunoassay. Cysteine codons in exons 10 and 11, specifically codons 609, 611, 618, 620, 630 and 634, were screened for the presence of mutations by sequence analysis. Specific mutations occurring at codons 768, 883 and 918 were screened for by restriction endonuclease digestion of PCR products.RESULTS The mutation at codon 918ATG → ACG was found in 21 of 32 (66%) MTCs and the mutation at codon 883GCT → TTT was found in one of 32 MTCs. Where possible, the presence of ‘germline‐type’ mutations in codons 609, 611, 618, 620, 630 and 634 were excluded. Ten MTCs did not have a mutation in codons 768, 883 or 918 of theRETproto‐oncogene. The presence or absence of the somatic mutation at codon 918 did not correlate with any of the above clinical characteristics.CONCLUSION Somatic mutations in theRETproto‐o

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.681503.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Polycystic ovaries have been diagnosed in more than 20% of premenopausal women using ultrasound. The aim of this study was to determine whether polycystic ovaries exist in post‐menopausal women.DESIGN Two groups of women were studied; group 1 consisted of 18 post‐menopausal volunteers and group 2 comprised 142 women, 94 of whom were post‐menopausal who had recently undergone coronary angiography.MEASUREMENTS Transabdominal and transvaginal ultrasound scans were performed and measurements made of uterine area, endometrial thickness and ovarian volume. The morphological appearance of the ovaries was also noted. Fasting blood samples were taken. Medical and menstrual questionnaires were completed.RESULTS Polycystic ovaries were found in 8/18 (44%) of group 1 and 60/142 (42%) in group 2. Polycystic ovaries were detected in 35/94 (37%) of the post‐menopausal women in group 2. Post‐menopausal women with polycystic ovaries had larger ovaries containing more follicles compared with post‐menopausal women with normal ovaries. Post‐menopausal women with polycystic ovaries had higher serum concentrations of testosterone and triglycerides than had post‐menopausal women with normal ovaries.CONCLUSIONS Polycystic ovaries can be detected in post‐menopausal women and have some of the same endocrine abnormalities which are evident in premenopausal women with polycystic ovaries, that is, raised serum concentrations of tes

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.676498.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history.DESIGN A cross‐sectional study of insulin sensitivity and lipids in a cohort of PCO subjects compared to weight and ethnic group matched controls.PATIENTS AND METHODS We have therefore investigated glucose tolerance, plasma lipids and lipoproteins in 19 lean (LP) and 55 obese (OP) patients with PCO and compared the results with those in 22 lean (LC) and 15 obese (OC) control women. Insulin sensitivity was measured in the same subjects with a short insulin (0.05 U/kg i.v. insulin) tolerance test (LP,n = 18; OP,n = 20; LC,n = 19; OC,n = 11).RESULTS Results are expressed as mean ± SEM or median (interquartile range). Fasting plasma glucose levels were similar in the four groups but the plasma glucose area was higher after oral glucose (75 g) in both the lean and obese PCOS groups than in their controls (LC 32.4 ± 0.7vsLP 35.2 ± 1.2,P < 0.01; OC 34.7 ± l.8 vs OP 37.8 ± 1.5 mmol/l/3 h,P < 0.01). Insulin sensitivity was significantly reduced in obese PCOS women (LC 196 ± 9vsLP 179 ± 9, NS; OC 168 ± 12vsOP 133 ± 9 mmol/l/min,P < 0.01). Total serum cholesterol levels were similar in the four groups but HDL2‐cholesterol was reduced in both obese and lean PCOS (LC 0.42 (0.38–0.62), LP 0.31 (0.26–0.44),P < 0.05; OC 0.34 (0.21–0.47), OP 0.21 (0.12–0.32) mmol/l,P < 0.01). Total HDL‐cholesterol was decreased significantly only in the obese PCOS group. Body mass index correlated significantly and negatively with total HDL‐cholesterol and with HDL2‐cholesterol levels both within the PCOS group and the control women. Using multiple regression insulin insensitivity contributes significantly beyond BMI to the low HDL‐cholesterol in women with polycystic ovaries.CONCLUSION Polycystic ovary syn

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.674495.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Women experience an age‐related decline in fertility despite regular ovulatory cycles and normal production of ovarian steroids. Growth hormone and IGF‐I are both reported to decline with age, and there is evidence that both hormones promote intraovarian actions of gonadotrophins. The purpose of this study was to characterize circulating levels of GH and IGF‐I in normal, older reproductive age women with ovulatory cycles.DESIGN Prospective, controlled.PATIENTS Twenty‐eight regularly cycling older (n = 16) and younger (n = 12) women were recruited for daily blood sampling throughout a menstrual cycle.MEASUREMENTS Serum obtained from daily blood sampling was analysed for LH, FSH, oestradiol (E2) and progesterone (P). Serum obtained from frequent sampling during the admission was analysed for pulsatile GH secretion. IGF‐I and GH binding protein (GHBP) were also measured in subsets of the two age groups.RESULTS All subjects exhibited normal patterns of LH, FSH, E2and P consistent with ovulatory cycles. There were no differences between the two age groups in integrated 24‐hour GH secretion or in GH pulse amplitude or frequency. There were no differences in GH secretion between the early follicular and midluteal phases when data were combined for the two subject groups. Plasma concentrations of IGF‐I were significantly lower throughout the cycle in the older women. There were no significant differences in levels of GHBP across the cycle or between the two age groups.CONCLUSIONS IGF‐I decreases with age in women without identifiable changes in the amount or pattern of GH secretion or in circulating GHBP concentrations. Decreased IGF‐I production may be related to decreased ovarian gonadotrophin sensit

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.670491.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVES The relative contributions of administered oestrogen and progestin to protection of the post‐menopausal skeleton remain unclear. We have compared the effect on spinal bone mineral density of continuous combined oestrogen/medroxyprogesterone therapy with that of unopposed oestrogen in late post‐menopausal women.DESIGN Observational study.SUBJECTS Seventy‐three osteoporotic post‐menopausal women attending the Auckland Hospital Bone Clinic. Twenty‐three hysterectomized women were treated with unopposed oestrogen (0.625 mg oral conjugated oestrogens daily), and 50 non‐hysterectomized women were treated with continuous combined oestrogen/medroxyprogesterone therapy (5 mg medroxyprogesterone acetate and 0.625 mg oral conjugated oestrogens daily).MEASUREMENTS Baseline and one‐year measurements of lumbar spine bone mineral density were performed using dual‐energy X‐ray absorptiometry.RESULTS After one year of therapy, spinal bone mineral density increased by 6.6% (95% confidence interval 5.6–7.6,P < 0.001vsbaseline) in the combined oestrogen/medroxyprogesterone therapy group, compared to 4.0% (CI 2.4–5.7,P < 0.001vsbaseline) in the unopposed oestrogen group (difference between means 2.6% (CI 0.8–4.4,P < 0.01).CONCLUSION In osteoporotic post‐menopausal women, one year of continuous combined oestrogen/medroxyprogesterone therapy is associated with a 65% greater increment in spinal bone mineral density than is observed in response to unopposed oestrogen. The prescription of combined oestrogen/progestin therapy should be considered in osteoporotic post‐menopausal women who have undergone hysterectomy, in order to maximize the sk

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.667488.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.688511.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.669490.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Large amounts of antigen may produce falsely low values in immunoradiometric assays due to the so‐called high dose, hook effect. The study was designed to identify the clinical and biochemical features of patients with pituitary macroadenomas in whom a high dose PRL hook effect was documented.DESIGN The clinical and biochemical features of four patients with the high dose PRL hook effect were compared with those of 54 patients with pituitary non‐functioning adenomas and 11 with macroprolactinomas who underwent transsphenoidal microsurgery between 1989 and 1994.MEASUREMENTS The presence of the high dose PRL hook effect was confirmed by an increase in the initial PRL concentration when the immunoradiometric assay was processed after dilutions of the serum. This phenomenon was observed in 5.8% (4/69) of patients with pituitary macroadenomas. Undiluted median (range) PRL levels were 9140 (l530–83850), 1530 (162–3210) and 2110 mU/l (1470–45 000) in patients with macroprolactinoma, non‐functioning macroadenoma and the hook effect, respectively. In patients with the hook effect, the median PRL levels increased to 384720 (317520–950 000) mU/l when the assay was performed after serum dilution. The proportion of males was 9.9% (1/11) in the macroprolactinoma group, 46.3% (25/54) in the non‐functioning macroadenoma group and 100% (4/4) in patients with the hook effect. Patients with prolactinoma and non‐functioning adenoma had mean tumour sizes of 20±9 and 27±11mm (SD), respectively, while in the hook effect group it was 51±10mm.CONCLUSION This study suggests that the high dose PRL hook effect is observed particularly in patients with very large tumours. The immunoradiometric PRL assay must be performed with serum dilution in order to overcome the high dose PRL hook effect in all new patients with pituitary macroadenomas

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.663486.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The few previous studies in which reassessment of GH status has been carried out in young adults treated with GH therapy for childhood GH deficiency concentrated on determining the incidence of ‘transient GH deficiency’. As the benefits of GH replacement therapy in adults become increasingly appreciated, it is likely that GH therapy started in childhood for GH deficiency will be continued into adult life in many of those with severe GH deficiency. The aim of this study is to determine how many patients who received GH replacement therapy in childhood until completion of growth have GH deficiency severe enough to be considered for GH replacement therapy in adult life.DESIGN Retrospective analysis of the peak GH responses to provocative stimuli performed at the time of diagnosis of GH deficiency in childhood and at the completion of growth after GH replacement therapy had been stopped.PATIENTS Eighty‐eight adults (49 male, 39 female) who had received GH therapy in childhood for a diagnosis of GH deficiency. The aetiology of the GH deficiency included craniopharyngioma, radiation induced associated with either a cerebral tumour or acute lymphoblastic leukaemia, histiocytosis‐X and idiopathic.MEASUREMENTS In childhood the original diagnosis of GH deficiency was based biochemically on the failure of the peak GH response to reach 20 mU/l during two provocative tests in 59 of the 88 patients and to a single test in the remaining 29. A total of 147 tests were performed, the most common being an insulin tolerance test (ITT,n= 72) and an arginine stimulation test (AST,n= 53).  At reassessment in young adult life 146 tests were performed (74 ITT, 64 AST). Severe GH deficiency was defined arbitrarily as a peak GH response of less than 9 mU/l to a single (n= 33) or to two (n= 55) pharmacological stimuli.RESULTS By definition all patients were considered GH deficient at the time of initial diagnosis. A peak GH response of less than 9 mU/l was seen in 64.8% at initial assessment and 60.2% at reassessment. Analysis in aetiological terms, however, showed that between assessments the incidence of severe GH deficiency increased in the group of radiation induced (48.8 vs. 55.8%) but decreased in the idiopathic group (78.1 vs. 53.1%). Out of the 55 patients who underwent two tests at reassessment, 47.3% of those with a GH peak less than 9 mU/l at one test had a GH peak greater than 9 mU/l at the second test. Fifteen of the 55 patients had additional pituitary hormone deficiencies and all 15 had a GH peak below 9 mU/l in both tests.CONCLUSIONS Our study suggests that all children who have received GH replacement therapy in childhood should undergo reassessment of GH status in young adult life. Between 40 and 60% of such patients merit consideration for GH therapy in adult life depending on the definition of severe GH deficiency in use. Patients with isolated GH deficiency should undergo two provocative tests of GH secretion, but those with additional anterior pituitary hormone deficiencies requ

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.671492.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY