ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8540862.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8680879.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Growth hormone serves many important functions in man. It influences carbohydrate, lipid and protein metabolism, regulates the secretion and action of a variety of other hormones, and interacts with the immune system. Its most studied role, however, as its name implies, is the orchestration of longitudinal growth, which occurs predominantly at the epiphyseal plate. Here, GH acts both directly and indirectly, through the systemic and local production of IGF‐I (Isakssonet al., 1987). A separate role for the GH/IGF‐I axis in the maintenance of normal bone mineral density (BMD) after epiphyseal closure is also apparent and is an area of active clinical investigation. In this review, we examine the effects of GH on mature bone, summarize the findings of studies on the skeletal effects of GH in adults, and consider the potential use of GH as an anabolic agent in the treatment of osteoporo

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8750885.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Pancreatitis is an unusual complication of the benign disorder familial hypocalciuric hypercalcaemia (FHH) such that it could represent a distinct subgroup of FHH. In order to study this, we investigated three FHH kindreds with recurrent pancreatitis for mutations of the extracellular calcium‐sensing receptor (CaR) to identify a possible common genetic aetiology for typical FHH and that associated with pancreatitis.PATIENTS AND METHODS Three FHH kindreds (18 affected, 14 unaffected members) in which the proband had presented with recurrent pancreatitis were identified. The entire 3234bp coding region of the CaR gene was examined by direct DNA sequencing using fluorochrome labelled dideoxy‐terminators. Mutations were confirmed and demonstrated to co‐segregate with FHH by restriction enzyme analysis.RESULTS Three novel heterozygous missense mutations (Asn178Asp, Arg220Gln and Pro221Ser) in the extracellular domain of the CaR were identified in each of the probands. These mutations, which co‐segregated with the hypercalcaemia, were not detected as common polymorphisms in 55 unrelated normocalcaemic controls.CONCLUSIONS Familial hypocalciuric hypercalcaemia with recurrent pancreatitis is associated with calcium‐sensing receptor mutations, and thus this variant has the same genetic aetiology as typical familial hypocalciur

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.750891.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Studies with GH substitution in GH‐deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End‐points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2per day) versus placebo treatment for 12 months.DESIGN Twenty‐nine patients (mean age 45.5±2.0 years) with adult‐onset GHD were studied in a double‐blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex‐matched subjects was included.RESULTS Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P<0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle : fat ratio (%) (placebo: 58 : 42 (baseline)vs58 : 42 (12 months); GH: 66 : 34 (baseline)vs72 : 28 (12 months) (P=0.002); normal subjects: 67 : 33 (P<0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over‐hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7±9.8 (baseline)vs51.6±8.2 (12 months); GH: 64.9±13.3 (baseline)vs73.5±13.6 (12 months) (P<0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF‐I levels (μg/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270±31 (12 months GH)vs156±8 (normal subjects (P<0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months.CONCLUSIONS (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo‐controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substi

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8720883.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Inter‐relationships between insulin sensi‐tivity and body weight in patients with hyperthyroidism remain incompletely understood. We have examined whether a mild excess of body weight exacerbates the metabolic abnormalities of spontaneous hyperthyroidism.DESIGN AND PATIENTS Insulin‐modified intravenous glucose tolerance tests were performed on 14 hyperthy‐roid women with body mass indices (BMI) ranging from 21 to 31 kg/m2. A control group of 19 healthy women matched for age and BMI was also studied.MEASUREMENTS Intravenous glucose tolerance (KG), first and second‐phase integrated insulin responses to glucose, the integrated glucose area under the curve (AUC), and minimal model parameters of insulin sensitivity (SI) and glucose effectiveness (SG) were determined.RESULTS Hyperthyroid women had mean KG, glucose‐induced insulin secretion and SG values similar to those in control women. The mean glucose AUC was higher in hyperthyroid patients (P<0.05). Lower insulin sensitivity was observed in hyperthyroid patients than in control women (SI=0.38±0.07 vs 0.59±0.07 l/min pmol 104(mean±SEM),P25 kg/m2,n=6) had a higher (P<0.05) second‐phase insulin response to glucose than normal weight patients, a higher glucose AUC (P<0.05) than normal weight patients and overweight controls (n=8), and a lower SI (P<0.05) than normal weight patients and overweight controls. SG was not influenced by BMI in hyperthyroid patients.CONCLUSIONS These results suggest that overall glucose tolerance was not significantly affected in normal weight hyperthyroid women. However, when a moderate excess of weight is also present, a stat

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8500860.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND It has been previously shown that food intake elevates circulating ACTH and cortisol levels, but no report has been published regarding the changes in circulating dehydroepiandrosterone (DHEA). DHEA was originally described as a weak androgen, but more recently it has been associated with a wide range of metabolic functions. In addition, previous studies have described a hyper‐responsive hypothalamo‐pituitary‐adrenal axis in obese subjects in response to various stimuli, but the specific response to food has not been studied.SUBJECTS AND DESIGN We studied the effect of food on the hypothalamo‐pituitary‐adrenal axis in 20 subjects of normal body mass index (BMI range 18–25) and also in a group of 12 obese subjects (BMI range 34–61). Levels of glucose, insulin, ACTH, cortisol and dehydroepiandrosterone were measured every 20 minutes.RESULTS A small rise in DHEA accompanies the rise in circulating ACTH and cortisol in response to food in both lean and obese subjects, but DHEA rose independently of cortisol and ACTH on the fasting day. In the obese subjects, food induced a significantly greater change in serum cortisol (peak cortisol rise (mean±SEM); normal‐weight group, 169±14%; obese group, 294±23%) and in the cortisol/DHEA ratio (area under the curve; normal‐weight group, 202±15%; obese group, 292±29%) than in the normal‐weight subjects. This difference was particularly notable in those with central‐type obesity (waist/hip ratio>0.80). A group of the normal, lean female subjects showed no cortisol rise after food intake.CONCLUSION Our results suggest that DHEA may vary independently of circulating cortisol, and that the cortisol response to food is enhanced in obese subjects, particularly in those with central obesity. We speculate that there may be a caused connection between the cortisol response to food in normal subjects, and the subsequent distribution of fat if such subjects ov

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8550865.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE There are only limited data on bone mineral density (BMD) in adult patients with 21‐hydroxylase deficiency (21‐OHD). We have defined the effects of different glucocorticoid substitution therapies on BMD and body composition in these patients.DESIGN Cross‐sectional.PATIENTS Thirty‐two adult patients with 21‐OHD.MEASUREMENTS Patients were examined auxologically and biochemically. BMD was examined in the left femoral neck and lumbar vertebrae 2–4 (L2–4) with dual X‐ray absorptiometry. The results were compared with national reference data.RESULTS Mean height was 170.1 cm (−1.36 standard deviation scores (SDS) for the men and 156.3 cm (−1.68 SDS) for the women. These were significantly less (P<0.001) than the mean national final heights. Mean BMDZ‐score ((raw score − population reference mean)/SD) was −0.52 in L2–4 and −0.83 in the left femoral neck. Both these values were significantly less than the reference mean values (P=0.045 and<0.001, respectively). Both current and long‐term mean glucocorticoid doses showed significant negative correlations with BMD in the left femoral neck as well as in L2–4. Patients substituted with hydrocortisone were less often over‐treated and had better BMDZ‐score means than patients substituted with prednisone, prednisolone or dexamethasone.CONCLUSIONS In the follow‐up of patients with 21‐hydroxylase deficiency, care needs to be exercised to keep the glucocorticoid substitution dose to a minimum. In most cases de

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8620871.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Cushing's syndrome is associated with psychiatric and psychological disturbances. The aim of this study was to ascertain the extent of mental illness in patients before and after treatment for Cushing's syndrome.DESIGN AND PATIENTS Patients with Cushing's syndrome were identified for a prospective study. Control patients were selected with pituitary adenomas secreting GH or PRL. The aim was to reassess patients after Cushing's syndrome had been treated.MEASUREMENTS Psychiatric symptoms were measured and classified using the Present State Examination (PSE), and analysed on the Catego Programme. The Hamilton Rating Scale (HRS) was used to measure depression. The Crown‐Crisp Experiential Index was used to measure common psychoneurotic symptoms (anxiety, phobia, obsession, somatic, depression and hysteria scales). The Eysenck Personality Inventory was used to assess extroversion and neuroticism. Cortisol, ACTH, and other hormones were measured by conventional methods. Parametric and non‐parametric tests were used where appropriate.RESULTS Catego analysis of psychiatric ratings showed only 8 patients of 43 with active Cushing's syndrome (19%) were normal. Psychiatric diagnoses were obtained as follows: neurotic depression in 20 (46%), possible neurotic depression in 1 (2%), reactive depression in 6 (14%), and non‐specific neurotic symptoms in 8 (19%). Additional Catego ratings of suspected other psychoses were made for 3 patients who were also depressed. None of these 43 patients with active Cushing's syndrome had ratings of schizophrenia or mania, obsessional neurosis or pathological anxiety. In the control group 13 (87%) were normal, 1 patient with acromegaly had an anxiety state and one patient with a prolactinoma had neurotic depression.It was possible to reassess the Present State Examination after treatment in 25 patients, when cortisol levels had been substantially reduced (to normal in 88%), the percentage rated as psychiatrically normal increased from 19 to 68 (χ2=11.7, 1 d.f.,P<0.01). Hamilton Rating Scale scores for depression showed significant improvements after treatment for Cushing's syndrome (mean decrease from 9.2 to 2.4,n=36,P<0.001). Crown‐Crisp experiential index data showed significant improvements in anxiety, somatic symptoms, and depression (n=25,P<0.05). Eysenck Personality Inventory assessments showed a significant improvement in neuroticism score (n=26P=0.016), but no significant change in extroversion (P=0.5) or lie score (P=0.6).CONCLUSIONS Most patients with Cushing's syndrome had significant psychiatric pathology, usually depressive illness. As cortisol levels were returned to normal there were significant improvements in scores for depression and anxiety. Management of patients with Cushing's syndrome should include careful assessment of psychological and

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8690878.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The mechanisms underlying the association between reduced size at birth and cardiovascular disease and non‐insulin‐dependent diabetes mellitus in adult life are not known. One possibility is that the intra‐uterine environment has permanent effects on the function or activity of the hypothalamo‐pituitary‐adrenal axis. We tested this by relating size at birth to the urinary excretion of adrenal androgen and glucocorticoid metabolites in a population sample of 9‐year‐old children.SUBJECTS AND METHODS One hundred and ninety children (89 boys and 101 girls) of known present height, weight and size at birth collected a 24‐hour urine sample. The urinary breakdown products of dehydroepiandrosterone sulphate and of cortisol and cortisone were measured by gas chromatography and their respective breakdown products summed (‘adrenal androgen metabolites’ and ‘glucocorticoid metabolites’). Excretion was expressed in μg/day.RESULTS Urinary adrenal androgen metabolite excretion was higher in children who had been light at birth. A 1‐kg decrease in birthweight was associated with a 40% (95% CI 9–79%) increase in metabolite excretion. Excretion was positively associated with current weight and age, but the relation with birth weight was independent of weight, age or sex. Urinary glucocorticoid metabolite excretion was positively associated with current weight, but not independently with age. The urinary excretion of total glucocorticoid metabolites was higher in children who had been light at birth, but the relation was best described as U‐shaped, with the highest average urinary glucocorticoid metabolite excretion being found in children who had been either light or heavy at birth. The U‐shaped (quadratic) relation persisted after adjustment for sex and current weight (Pfor quadratic term 0.006).CONCLUSION These findings suggests that the intra‐uterine environment, as measured by fetal size at birth, has long‐lasting effects on the functi

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.8560864.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY