ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02590.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVEGrowth hormone replacement of adults with childhood onset GH deficiency results In an Increase In bone mineral density (BMD) after 6‐12 months of OH replacement. By measuring BMD 12 months after discontinuation of GH replacement we aimed to Investigate whether there is an effect of GH replacement on BMD persisting after GH has been withdrawn.DESIGNBMD was measured 13 ± 1 (mean ± SE, range 11‐16) months after discontinuation of OH replacement. PATIENTS Ten adults, age 23·;2 ±1·;4 (range 18·8‐32·4) years, with childhood onset isolated GH deficiency (2 idiopathic, 8 irradiation induced) who had previously completed a study of the effect of 12 months of OH replacement on BMD.MEASUREMENTSForearm cortical bone mineral content (BMC) was measured using single‐photon absorptlometry at the proximal site of the distal forearm. Forearm integral BMC at the ultradistal site of the forearm and bone width at both proximal and ultradistal rites of the distal forearm were measured by the same technique. Vertebral trabecular BMD was measured using quantitative computed tomography.RESULTSForearm cortical BMC was significantly greater than that measured at the time of discontinuation of OH (1·48 ±0·04 vs 1·44 ± 0·05 g/cm). There was no significant change in forearm integral BMC or in vertebral trabecular BMD after discontinuation of OH. There was no significant change in bone width at proximal and ultradistal sites of the distal forearm after discontinuation of GH.CONCLUSIONAfter discontinuation of OH replacement the further increase In forearm cortical bone mineral content without a significant Increase In forearm bone width suggests that the Increase In cortical bone mineral content Is due to a persisting effect of previous GH replacement, and not to further spontaneous attainment of bone mass before peak bone mass lo reached. These findings emphasize the importance of continuing to monitor bone mass after the stimulus to Increase bone turnove

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02591.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUNDCalcium channel antagonist therapy in humans has been associated with changes In anterior pitultary, thyroid and adrenal hormone secretion. Human studies assessing effects of calcium channel antagonists on calclotropic hormones have been few and typically involved small numbers of subjects studied for short periods of time. Few of these previously published studies have included women. The endocrine effects of calcium channel antagonists in women have become increasingly important as more women are taking these agents for diseases such as hypertension, angina, Raynaud's phenomenon and migraine.OBJECTIVETo assess both acute and chronic effects of calcium channel antagonists on calclotropic hormones in women.DESIGNA four‐week prospective, randomized trial.SUBJECTSTwenty‐nine premenopausal women, randomly assigned to receive either 240 mg of sustained release verapamil or 30 mg of sustained release nifedipine daily.LABORATORYEND‐POINTS Total and ionized serum calcium, phosphate, creatinine, parathyrold hormone (PTH), parathyroid hormone‐related protein (PTHrP) and calcitonin, measured at baseline, after 24 hours, and 28 days of treatment.RESULTSTotal and ionized calcium, phosphate, creatinine, PTHrP and calcitonin levels were not altered significantly after 24 hours or 28 days in any of the subjects, when compared to baseline. There were no significant differences in PTH levels after 24 hours or 28 days of verapamil treatment. There was a significant increase in serum PTH levels after 24 hours of nifedipine therapy; however, these differences were not evident after 28 days of therapy.CONCLUSIONSThe short‐term administration of nifedipine results in increased release of parathyroid hormone; however, long‐term administration has no significant effect on the concentrations of calclotrop

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02592.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVETo determine the presence of abnormalities of theMENZAregion of theretproto‐oncogene in phaeochromocytomas/paragangllomas (PHAEO) of different aetiologies.DESIGNTotal RNA was extracted from tumours and used as templates for reverse transcriptase polymerase chain reactions. Aretprimer pair, which encompasses the region which is mutated in the germ‐line of patients with MEN 2A, was used. The resulting 262‐bp product was sequenced.PATIENTSTen PHAEOs were examined. Four tumours were from von Hippel‐Lindau disease patients; five were sporadic, Isolated tumours; one from a patient with multiple endocrine neoplasia type 2A (MEN 2A). The medullary thyroid cancer from the single MEN 2A patient was also examined.RESULTSA heterozygous TGC to CGC mutation of codon 634 (cysteine to arginine) was found In the PHAEO and medullary thyroid cancer from the MEN 2A patient. The 262‐bpretfragment was not found in two tumours (one malignant PHAEO and one secretory paraganglloma), although the Intra‐cellularrettyrosine kinaw domain was detected in these tumours. The cysteine codons were normal in all other non‐MEN 2A PHAEOs.CONCLUSIONMutations of key cysteine codons of theretproto‐oncogene may be spe

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02593.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVEOestrogens, androgens and anti‐endocrine drugs such as tamoxifen and aminoglutethimide influence plasma Insulin‐like growth factor‐I (IGF‐I). IGF‐I, in turn, has been found to stimulate the peripheral aromatasein vitro.The aim of this study was to examine relations between sex hormones, IGF‐I and insulin‐like growth factor binding protein‐1 (IGFBP‐1) In post‐menopausal women with breast cancer.DESIGNTo measure plasma sex steroids, sex hormone binding globulin (SHBG), IGF‐I, IGFBP‐1, Insulin and urinary oestrogen metabolites In post‐menopausal women with breast cancer not receiving any endocrine therapy.PATIENTSThirty‐two patients had fasting blood samples obtained between 0800 and 1000h. A sub‐group of 10 patients had 24‐hour urine oestrogen metabolites determined.MEASUREMENTSPlasma steroids and proteins were measured by radioImmunoassays. Urinary oestrogens were measured by GC‐MS.RESULTSSHBG correlated negatively with plasma androstenedione (P<0·001), insulin (P<0·001), IGF‐I, height and plasma oestrone sulphate (P<0·025 for all), but positively with plasma IGFBP‐1 (P<0·025). IGFBP‐1 correlated negatively with IGF‐I (P<0·001) and the testosterone/SHBG ratio (P<0·05). Neither IGF‐I nor IGFBP‐1 correlated with any of the plasma or urinary sex hormones or with the oestrone/androstenedione and oestradiol/testosterone ratios.Multivariate analysis revealed plasma SHBG to correlate positively with IGFBP‐1 (P= 0·029) and negatively with Insulin (P= 0·031). Plasma IGFBP‐1 correlated negatively with IGF‐I (P<0·0001) but not with insulin.CONCLUSIONOur results do not suggest any influence of plasma sex steroids in physiological concentrations on IGF‐I or IGFBP‐1 in post‐menopausal breast cancer patients, nor do they indicate IGF‐I at physiological concentrations Influence

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02594.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVESomatostatin is secreted from thyroid C‐cells and seems to play an Important part In the regulation of calcitonin secretion. We therefore evaluated the usefulness of somatostatin receptor scintigraphy in the localization of tumour tissue in patients with persistent medullary thyroid carcinoma.DESIGNA prospective clinical study.PATIENTSThe series consisted Of 26 patients with elevated calcitonin levels after total thyroldectomy for histologically proven medullary thyroid carcinoma.METHODSSomatostatin receptor scintigraphy using111In‐pentetreotide (Octreoscan) was performed in all patients and the results correlated with histology, ultrasonography, computerized tomography, magnetic resonance Imaging, plain radiography, bone scintigraphy and selective venous Catheterization. calcitonin and carcinoembryonic antigen levels were measured.RESULTSThe sensitivity of somatostatin receptor scintigraphy for localization of persistent medullary thyroid carcinoma was 57% in patients with histologically proven disease. The results depended on tumour mass (low sensitivity (33%) in minimal residual disease) and on the location of metastases (Insensitive in detecting liver metastases).CONCLUSIONSSomatostatin receptor scintigraphy is of value as an additional diagnostic tool in localizing medullary thyroid carcinoma, especially pulmonary metastases. It is of minor importance in detecting minimal residual dise

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02595.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVEThe aim of this study was to develop an assay for the measurement of thyroid blocking antibodies (TBAb), based on the ability of patient serum to inhibit TSH stimulated3H‐cAMP production following incubation of FRTL‐5 or JPOS cells with3H‐adenine. The assay was then used to evaluate a child born with neonatal hypothyroidism.DESIGNThe levels of TBAb, TSAb (thyroid stimulating antibodies), TBII (TSH binding Inhibitory antibodies), and the thyroid antibodies anti‐thyroid peroxidase and thymoglobulin antibodies were measured in both mother and child over a 6‐month post‐natal period.PATIENTThe assay for TBAb was used to evaluate a child born with neonatal hypothyroidism whose mother had a history of hypothyroidism due to Haehimoto's thyrolditis. A99mTc pertechnetate scan showed no evidence of functioning thyroid tissue. At 20 months of age an ultrasound verified a normally positioned thyroid.RESULTSInitially, high levels of TBII and antithyroid antibodies were present in the serum of both mother and child. In both, the levels of TSAb were undetectable but there were significant levels of TBAb. The levels of TBAb decreased to control levels in the child within 2 months of birth but remained elevated in the mother's serum.CONCLUSIONSThis case of neonatal hypothyroidism associated with the passage of thyroid blocking antibodies demonstrates the utility of this new assay in the differential diagnosis of neonatal hyp

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02596.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUNDThe natural history of thyroid associated ophthalmopathy is poorly documented, although It is widely thought that many cases Improve spontaneously with time. This has Important Implications in the management of patients and is also a critical factor when assessing the effects of different treatments.OBJECTIVETo document the natural history of thyroid associated ophthalmopathy, 59 patients were studied longitudinally and the severity of eye disease documented at regular Intervals.METHODSFifty‐nine patients with thyroid associated ophthalmopathy who had not received Immunosuppressive or surgical treatment for their eye disease, were recruited from a combined thyroid‐eye clinic. They were assessed at presentation and at 3–6‐monthly Intervals for a median of 12 months. The eyes were assessed by separate and objective measurements relating to the status of the eyelids, cornea, extraocular muscles, proptosis and optic nerve function. In addition, a scoring system based on the above measurements was used to grade the overall severity of eye disease.RESULTSThirteen patients (22%) Improved substantially, 25 patients (42·4%) showed minor Improvement, 13 patients (22%) did not change, and 8 patients (13·5%) deteriorated progressively, to the extent that Immunosuppressive treatment was considered to be necessary.CONCLUSIONSA significant proportion of patients with thyroid associated ophthalmopathy (64·4% in the present series) Improve spontaneously so serial assessment plays an Important part in deciding which patients require Immunosuppressive treatment. These findings also support the view that clinical trials designed to test the efficacy of new treatments in thyroid associated ophthalmopathy should be scrupulously controlled to allow for the natural tendency towards

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02597.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVEDegradation of AVP by placental vasopressinase may precipitate gestational diabetes insipidus, which in some cases is accompanied by pre‐eciampsia. Abnormally elevated vasopressinase has also been reported in pre‐eciampsia without diabetes Insipidus. This association between excessive vasopressinase production and pre‐eciampsia might be explained if the products of AVP degradation by vasopressinase retained pressor activity even after anti‐diuretic activity had been destroyed. Recent evidence indicates that such products may raise blood pressure in rats. The objective of this study was, therefore, to purify vasopressinase and investigate its action on both the V1and V2receptor‐stimulating activity of AVP.DESIGNVasopressinase was purified from pooled pregnancy serum by ammonium sulphate precipitation, followed by sequential Ion exchange, lentil lectin affinity and gel filtration chromatography. Purified enzyme was then used to degrade AVP and the loss of both immunoreactivity and biological activity monitored. Loss of V1receptor‐stimulating activity and V2receptor‐stimulating activity was compared by two‐way ANOVA.PATIENTSBlood was obtained from healthy women between week 34 and the end of pregnancy. Pooled serum from 20–30 patients was used as starting material for the purification of vasopressinase.MEASUREMENTSAVP immunoreactivity was measured by radioimmunoassay, V1receptor‐stimulating activity by a platelet aggregation bioassay, and V2receptor‐stimulating activity by adenylate cyclase stimulation in LLC‐PK1target cells.RESULTSPurified vasopressinase was a dimeric protein of molecular weight 330 kDa, which cleaved the synthetic substrate S‐benzyl‐l‐cystelne‐4‐nitroanilide with aKmof 0·33 mM. Incubation of AVP (0·1 mm) with vasopressinase (0·66 g/I) at 37°C led to a parallel loss of both AVP immunoreactivity and biological activity. The rates of loss of V1and V2receptor mediated activities were not significantly different.CONCLUSIONSWe report the first direct comparison between the loss of V1and V2receptor mediated activities of vasopresrinase degraded AVP. There was no significant retention of V1, relative to V2, receptor mediated activity. AVP degradation products are unlikely to be

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02598.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVEChronic treatment with 17βoestradlol (E2Implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post‐menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post‐menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum.DESIGNSerum samples were obtained from 20 post‐menopausal women, mean age 60 years (range 50–72 years), treated with continuous dally oral medication of 2 mg E2combined with 1 mg norethisterone acetate (NETA). FSH, LH and E2in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0·1% agarose suspension. Sera from 20 post‐menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post‐menopausal women treated with E2Implants and on women with normal menstrual cycles.RESULTSThe E2level in the oral‐E2+ NETA treated women was 198‐610 pmol/l, within the range expected during the mid‐luteal phase of the normal menstrual cycle and similar to that of the group of women with an E2Implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P<0·001), the E2Implant group (P<0·001) and at the follicular phase of the cycle (P<0·01). The mean FSH level was slmllar to that of the folllcular phase and the E2implant group but lower than that of the controls (P<0·001) and higher than at the luteal phase of the cycle (P<0·01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P<0·001) but more acidic than those for the E2Implant group (P<0·01;P<0·001) and for different phases of the menstrual cycle (P<0·05;P<0·001). The mean degree of charge heterogeneity of FSH was larger (P<0·01), while that of LH was smaller (P<0·01), than for the controls. The mean concentrations of SHBG in the oral E2+ NETA group, the E2implant group and the controls were similar.CONCLUSIONChronic oral therapy with 2mg 17β oestradiol combined with 1 mg norethisterone in post‐menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E2Implant and the oral E2+ NETA treated groups may be due to the differences in route of administration of E1or to th

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02599.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY