ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03006.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARYOBJECTIVES Weight gain had previously been thought to be due to increased calorie intake alone though no information on its effect on total energy expenditure is available in humans. We therefore assessed whether weight gain associated with glucocorticoids is due to a reduction in energy expenditure.DESIGN We performed an open study with 1 mg of betamethasone given orally twice a day for 21 days.SUBJECTS Seven healthy female volunteers, age range 26–55 years, body mass index 19 to 40, mean 27 kg/m2.MEASUREMENTS Total free living energy expenditure was measured by the doubly labelled water method (D218O), resting metabolic rate by ventilated hood indirect calorimetry and fat free mass from the dilution volume of oxygen‐18 labelled water. Body composition and components of energy expenditure were assessed before and during the final 14 days of betamethasone administration.RESULTS Weight increased by a mean of 1·2 kg (P<0·05) because of a significant rise in fat mass (1·5 kg) with no change in fat free mass. Resting metabolic rate remained unaltered on betamethasone but total energy expenditure increased in all subjects with a significant mean rise of 26% from 11·7 to 14·7 MJ/24 h (P<0·05). The energy component of physical activity with thermogenesis increased on average 52% (from 5·8 to 8·9 MJ/24 h;P<0·05). The rise in energy expenditure was still apparent after correction for the increase in body weight. Fasting respiratory quotient (RQ) increased from 0·81 to 0·86 with no change in fasting blood glucose. Betamethasone did not result in an energy sparing effect on the two components of energy expenditure studied.CONCLUSIONS Body weight increased on betamethasone entirely due to an increase in fat mass. This occurred despite a rise in total energy expenditure which involved specifically that component accounted for by physical activity plus thermogenesis. The most likely explanation is that betamethasone increased dietary energy intake significantly in excess of expenditure. We estimate that an average extra energy intake of 2·8 MJ/day would have had to be consumed for this rise in fat mass to occur even before taking into account the energy intake cost of the rise

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03007.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES 18‐Oxocortisol (18oxoF) shares structural characteristics with cortisol and aldosterone and is secreted from the adrenal cortex. It has been reported that 18oxoF has weak gluco and mineralo‐corticoid activities and increases blood pressure when administered to animals. We tried to clarify the characteristics of the production of 18oxoF in patients with adrenocortical disorders compared with the control subjects.DESIGN AND PATIENTS In patients with primary aldosteronism due to aldosterone producing adenoma (APA) (n= 21) and Cushing's disease or syndrome (Cushing's diseasen= 13; adrenocortical adenoman= 10), plasma 18oxoF level early in the morning following an overnight fast was evaluated as well as plasma cortisol and aldosterone levels.RESULTS The plasma 18oxoF levels were significantly higher in the patients with adrenocortical disorders than in control subjects. The ratios of 18oxoF/cortisol and 18oxoF/ aldosterone were high in APA and in Cushing's disease and syndrome patients, respectively. In the control subjects and combined group of patients with Cushing's disease and syndrome, plasma 18oxoF level significantly correlated with plasma cortisol level but not with aldosterone level. However, in APA patients plasma 18oxoF level correlated significantly with both cortisol and aldosterone levels.CONCLUSION The production of 18oxoF was elevated as a result of the hyperactivity of 18‐hydroxylase and excess cortisol production in APA patients and in patients with Cushing's disease and syndrome, respectively. An excess 18oxoF production could be playing a role in the pathogenesis of hypertension in these patients. The correlation of plasma 18oxoF levels with plasma cortisol and aldosterone levels suggests that the production of 18oxoF is more dependent on the supply of cortisol than on 18‐hydroxylase activity in normal subjects and patients with Cushing's disease and s

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03008.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES While it has been shown that atrial natriuretic factor (ANF) is able to inhibit CRH‐stimulated ACTH secretionin vitro, in normal men conflicting results on its effect on ACTH/cortisol responses to insulin and CRH have been reported. Since no data are available concerning the possible influence of ANF on the hypothalamic‐pituitary‐adrenal axis in states of ACTH hypersecretion, the effect of ANF on pituitary‐adrenal function in basal conditions and after CRH stimulation has been investigated in patients with Cushing's (n= 4) and Addison's disease (n= 4).DESIGN On two different days all patients underwent the following procedures: (a) α‐human ANF was infused, after a priming dose of 100 ng i.v., at a rate of 0·01 μg/kg/min over 5 hours. After 120 minutes of ANF infusion, oCRH (1 μg/kg) was i.v. injected as a bolus; (b) vehicle infusion was given over 5 hours and at 120 minutes oCRH was injected. Plasma ANF, ACTH, cortisol, aldosterone, renin activity and K+were measured; heart rate and blood pressure were monitored.RESULTS In Cushing's disease plasma ANF rapidly increased within 30 minutes of the exogenous peptide infusion (from 27 ± 5 to 73 ± 14 pmol/l; mean ± SE), whereas in the vehicle study its concentration was unchanged. During the first 2 hours of both tests no significant modifications in ACTH levels were observed. After CRH the plasma ACTH peak was unchanged. Serum cortisol levels progressively declined during the first 2 hours of ANF infusion (from 778 ± 150 to 461 ± 48 nmol/l;P<0·05), whereas no changes were observed during vehicle. After CRH serum cortisol rose to similar peaks. Plasma aldosterone levels were significantly reduced during the first 2 hours of ANF infusion (from 81 ± 20 to 35 ± 7 pmol/lP<0·05), whereas no changes were found during vehicle. A similar aldosterone rise was induced by CRH during either vehicle or ANF. Mean plasma renin activity slightly declined and the changes were similar on both occasions. In Addison's disease ANF levels rose within 30 minutes of the peptide infusion (from 12·1 to 49·8 pmol/l), while they were unchanged during vehicle. A slight decline in ACTH levels in the first 2 hours was observed during either vehicle or ANF infusion. After CRH the plasma ACTH peaks were similar. Mean plasma renin activity was unaffected by vehicle, while ANF caused a decline during the first 2 hours (from 13·4 ± 0·8 to 7·7 ± 0·3 ng/ml/h). In all patients, heart rate, blood pressure and K+were only slightly affected on both occasions.CONCLUSIONS (1) In patients with corticotrophin hypersecretion ANF does not influence basal and CRH‐stimulated ACTH secretion; (2) in Cushing's disease ANF inhibits cortisol and aldosterone basal secretion; this effect is not mediated by ACTH and i

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03009.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES Various studies have demonstrated coexistence of ovarian and adrenal hyperandrogenism in women. This study was designed to determine whether testosterone can increase the response of the adrenal gland to stimulation by adrenocorticotrophin (ACTH).DESIGN Non‐randomized intervention in a university teaching hospital.PATIENTS Twenty androgen‐treated female‐to‐male transsexual patients (10 ovariectomized and 10 non‐ovariectomized) and 10 normal female controls.MEASUREMENTS ACTH stimulation tests were performed in all subjects. Baseline values and the increase above baseline values after ACTH stimulation were assessed for cortisol and the adrenal androgens androstenedione, dehydroepiandrosterone and dehydroepiandrosterone‐sulphate.RESULTS Increases in levels of cortisol, androstenedione and dehydroepiandrosterone after administration of ACTH were greater in testosterone‐treated transsexual patients than controls.CONCLUSION We conclude that testosterone increases the response of the adrenal gland to stimul

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03010.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES The ACTH stimulation test examines adrenal responsiveness but may not examine the entire hypothalamic‐pituitary‐adrenal (HPA) axis and requires parenteral administration. The cortisol response to hypoglycaemia provides an index of activity of the entire HPA axis but is demanding for patients and medical staff. The aim of the present study was to examine the performance of the overnight single‐dose metyrapone test as it provides a simple alternative test for HPA axis function.DESIGN Audit of the overnight metyrapone test performed in one centre between 1979 and 1991.PATIENTS Three hundred and ninety‐eight patients underwent 576 tests. Comparisons between the responses to metyrapone and the ACTH stimulation test and of the responses to metyrapone and insulin induced hypoglycaemia test were possible in 87 and 17 patients respectively.MEASUREMENTS Following the midnight administration of metyrapone tablets, 30 mg/kg orally, blood samples were obtained between 0800 and 0930 h for radioimmunoassay of both 11‐deoxycortisol and cortisol.RESULTS Five hundred and seventy‐six metyrapone tests were performed on 398 patients with no serious side‐effects encountered. Andrenal insufficiency was diagnosed in 105 patients. Of these, 18 had a primary adrenal disorder and 87 had a disorder of the hypothalamic‐pituitary unit. One hundred per cent concordance between the metyrapone, the ACTH and the hypoglycaemia test was seen in patients with primary adrenal insufficiency. In 19 patients with secondary adrenal insufficiency, who underwent both the metyrapone and the ACTH tests, discord between these two tests was observed in 10 patients (53%). Nine of these patients demonstrated a normal response to ACTH and a subnormal response to metyrapone. In only one patient was an abnormal cortisol response to ACTH associated with a normal response to metyrapone. In contrast, in 17 patients discord between the metyrapone and the hypoglycaemia test was seen in only 1 patient who demonstrated a normal response to the metyrapone test and a subnormal response to hypoglycaemia.CONCLUSION Since the metyrapone test gives similar information about hypothalamic‐pituitary axis function as does the hypoglycaemia test, we recommend the use of the overnight metyrapone test as a safe, simple and reliable index of the hypothalamic‐pituitary axis integrity. The ACTH stimulation test should not be used for patients suspected of having secondary ad

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03011.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES The assessment of insulin sensitivity requires an accurate and reproducible technique. The short insulin tolerance test is a simple and rapid method for screening large numbers of subjects when the fasting glucose level is normal. Conventionally, an insulin dose of 0·1 units/kg is used, but this may result in symptomatic hypoglycaemia in healthy thin subjects who are insulin sensitive. In order to overcome this problem we have employed a lower dose of insulin and have studied the reproducibility of this modified technique comparing it with the euglycaemic hyperinsulinaemic clamp.DESIGN Subjects were studied on two separate occasions, once by a short insulin tolerance test and on a second occasion by either a euglycaemic hyperinsulinaemic clamp (insulin infusion of 40 mU/m2/min) or a repeat short insulin tolerance test.PATIENTS Eleven healthy subjects were studied twice with a short insulin tolerance test. A further 10 healthy subjects received a short insulin tolerance test on one day and a euglycaemic hyperinsulinaemic clamp study on another occasion.MEASUREMENTS Insulin sensitivity was measured in the short insulin tolerance test using the slope of arterialized blood glucose concentration from 3 to 15 minutes after an intravenous bolus of short‐acting insulin, 0·05 units/kg body weight. In the clamp study, insulin sensitivity was derived from the average amount of glucose infused at steady state (M) and the mean plasma insulin level (l).RESULTS In the short insulin tolerance test no subject developed symptomatic or biochemical hypoglycaemia, defined as a blood glucose<2·2 mmol/l. The (mean ± SEM) insulin sensitivities for the 11 subjects studied twice were 174±10 and 179±11 μmol/l/min with a coefficient of variation of 6·9±2·6%. There was a close correlation between insulin sensitivity derived from the short insulin tolerance test and that obtained from the euglycaemic clamp studies (so‐calledM/lratio) in the same subjects (r= 0·81;P<0·005).CONCLUSION The short insulin tolerance test employing 0·05 units/kg insulin is a safe, valid and reproducible method for the assessment of ins

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03012.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses to a mixed meal in a dose dependent fashion in normals and in patients with non‐insulin dependent diabetes. We have studied the effects of pirenzepine on plasma insulin, plasma glucose, growth hormone (GH), androstenedione, testosterone, insulin‐like growth factor‐I (IGF‐I) and IGF binding protein 1 (IGFBP‐1) responses to a mixed meal in obese clinically hyperandrogenic women with the polycystic ovary syndrome.SUBJECTS AND METHODS Six obese women with polycystic ovary syndrome (BMI range 27·3–39·8 kg/m2) were studied in random sequence, and received either placebo or pirenzepine (single doses of 50, 100, or 200 mg) one hour before a standard test meal. Blood was sampled every 15 minutes for 2 hours after the meal and every 30 minutes thereafter for a total of 4 hours.RESULTS Mean fasting plasma insulin concentrations were increased. Peak post‐prandial plasma insulin concentrations were reduced significantly by all three doses used. Post‐prandial integrated plasma insulin concentrations were reduced by the two higher doses. Peak postprandial plasma glucose concentrations were also reduced. The late post‐prandial GH surge was significantly suppressed by all three doses. However, plasma androstenedione, testosterone, IGF‐I and IGFBP‐1 concentrations were not significantly different when placebo was compared with pirenzepine 200 mg.CONCLUSIONS Acute cholinergic muscarinic blockade with pirenzepine significantly reduces meal stimulated plasma insulin and plasma glucose concentrations in clinically hyperandrogenic women with polycystic ovary syndrome. The ability of pirenzepine to reduce plasma insulin without worsening glycaemia is a particular advantage and may be therapeutically relevant. Further studies are under way to assess the usefulness of pirenzepine in long‐term suppression of plasma insulin

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03013.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES Acute oral administration of dexamethasone (DEX) stimulates growth normone (GH) release at 3 hours in normal controls and provides us with a novel probe with which to study the somatotrophic axis. In affective illness GH release is subnormal In response to a number of stimuli. We decided to investigate the acute effects of DEX‐induced GH release in depression.DESIGN A between subjects parallel group design was employed.METHODS Baseline levels of GH and cortisol were taken after which 4 mg of oral DEX was administered. Plasma samples for GH estimation were taken at +60, +180, + 240 and + 300 minutes.PATIENTS Sixteen normal subjects and 16 unipolar, non‐psychotic, melancholic DSM‐111R major depressives were studied. Depressed subjects had to score over 17 on the Hamilton Depression Rating Scale; the mean ± SEM scores were 27·4±1·0.MEASUREMENTS Plasma GH and cortisol levels were measured by radioimmunoassay.RESULTS Baseline mean ± SEM GH levels (depressives 2·4 ±0·6 mU/l; controls 2·6 ±0·4 mU/l) did not differ significantly between the two groups (P<0·28). DEX‐induced GH secretion was subnormal in depressives as opposed to controls (2·1±0·7 vs 19·4±2·2 mU/l,P<0·001). There were significant differences between the two groups at 60, 180 and 240 minutes (P<0·05). Baseline cortisol values were significantly different between the two groups (depressives 303·3 ±31·5 nmol/l; controls 138 ± 4·7 nmol/l). An analysis of covariance, with cortisol as a covarlate, still found the depressives to have significantly subnormal GH responses as compared to the control group (P<0·05).CONCLUSION Dexamethasone‐induced GH

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03014.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

OBJECTIVES The investigation of the antibody response in thyroid‐associated ophthalmopathy (TAO) using different antigens and assays has given inconsistent results. We have analysed antibodies against eye muscle and control antigens in a large group of TAO patients to assess whether specific eye muscle antibodies exist in TAO. We have also evaluated the presence of IgA and IgM class antibodies and examined IgG subclass distribution.DESIGN Sera were obtained from all patients (TAO, Graves' disease without ophthalmopathy and Hashimoto's thyroiditis) within one year of diagnosis. Sera were also collected from healthy controls, with no family history of autoimmune thyroid disease.PATIENTS Thirty‐eight patients had Graves' disease with Grade III or greater TAO; 15 patients had Graves' disease without ophthalmopathy and nine had Hashimoto's thyroiditis without any eye signs. The control group consisted of 14 subjects.MEASUREMENTS Antibodies against porcine eye and skeletal muscle, human eye (membrane and soluble antigen) and skeletal muscle, human thyroid microsomal and thyroglobulin antigens and dermal and orbital fibroblast antigens were assessed using ELISA. Antibody isotypes and IgG subclasses were studied for porcine and human eye muscle antibodies. Eye muscle (porcine and human) and orbital fibroblast antibodies were further analysed by immunoblotting.RESULTS There were no significant differences in the ability of either IgG or IgA in sera from the different groups to bind porcine and human eye muscle antigens. There was a significant correlation (P<0·0001) between the binding to porcine eye muscle and skeletal muscle antigens (for both IgG and IgA). There was no difference between sera from TAO patients and control subjects in their binding to eye muscle fibroblasts for both IgG and IgA antibodies. However, IgA antibody activity against dermal fibroblasts differed significantly between TAO patients and controls (P<0·05). By immunoblotting, the frequency of IgA antibodies recognizing 21 kDa (40% of patients) and 62 kDa (52%) bands in porcine eye muscle blots and 20, 24 and 38 kDa bands in blots of human eye muscle (soluble) antigen differed significantly between patients with TAO and controls (P<0·05 in all cases). IgG antibodies recognizing 80 and 92 kDa bands in blots of the subcellular membrane antigen prepared from orbital fibroblasts were found more frequently in patients with TAO compared with controls (P<0·05 in both cases).CONCLUSIONS We found no evidence that eye muscle membrane or fibroblast antibodies are present in a significant proportion of TAO patients, using ELISAs based on antigens prepared from several sources. We have also failed to demonstrate the presence of previously described specific, TAO‐associated antibodies, including those directed against a 64 kDa protein in eye muscle and a 23 kDa protein in fibroblasts. IgA class antibodies reactive with orbital components appeared to be more strongly associated with TAO than those of the IgG class, though even this relationship is weak. These results suggest that antibodies are of secondary importance in the pathogenesis of TAO, which is most likely a T cell‐mediat

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb03015.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY