摘要:

SummaryBACKGROUND Reduction of GH concentrations in acromegalic subjects may improve the increased mortality associated with the condition. Audit of the biochemical outcome of the management of acromegaly is, therefore, important.OBJECTIVES (1) To audit the biochemical ‘cure’ rate of acromegalic patients treated by surgery and/or radiotherapy under the care of the South Birmingham Endocrine Clinic. (2) To assess the correlation between random or basal GH with IGF‐I and nadir GH during an oral glucose tolerance test.DESIGN AND MEASUREMENTS Ascertainment Of acromegalic patients from a pituitary database. Mode of therapy, pretreatment GH, pretreatment tumour size, post‐treatment GH, post‐treatment IGF‐l and post‐treatment nadir GH were recorded. Biochemical cure was defined as a most recent random or basal GH<5 mU/l. Cure rates were determined.PATIENTS Eighty‐nine acromegalic patients were Identified as having received surgery and/or radiotherapy. In 35/89 (39%) the most recent GH was<5 mU/l. The cure rate following surgery was 26/78 (33%). This was not significantly associated with tumour size, but was associated with pretreatment GH concentration (x2= 7.1, 2d.f., P<0.05). Random/basal GH showed a log‐linear association with IGF‐I,r= 0.72, and a linear association with nadir GH, r = 0.93.CONCLUSIONS Biochemical cure of acromegaly was more strongly associated with pretreatment GH than with tumour size. Random/basal GH measurements are useful and convenient for the audit of treatment outcome in acromegaly. Ways of improving the biochemical outcome of acromega

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02913.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02914.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The use of preoperative imaging in patients with hyperparathyroidism remains controversial. Many of the available techniques are insufficiently sensitive and specific to justify their routine use. We have evaluated the Sensitivity and specificity of99mTc‐sestamibi scintigraphy in the management of patients with different forms of hyperparathyroidism.DESIGN Preoperative imaging evaluation was carried out by sclntigraphic detection of pathological parathyroid glands using99mTc‐sestamibi as a radiotracer; confirmation of scan findings was obtained surgically.PATIENTS A group of 25 patients with primary (n= 21) or secondary (n=4) hyperparathyroidism were studied. All were considered for surgical treatment.MEASUREMENTS In all cases parathyroid imaging was carried out by99mTc‐sestamibi scintigraphy together with at least one other imaging technique which included CT‐scan, ultrasonography, MRI or201TI/99mTc subtraction scintigraphy. Blood tests included measurements of total calcium and PTH.RESULTS99mTc‐sestamibi scintigraphy correctly localized 20 out of 21 adenomas, giving a sensitivity of 95.2%, markedly higher than that obtained with the other imaging techniques (ultrasonography 75%,201TI/99mTc subtraction scintigraphy 57.1%, CT‐scan 41.7% and MRI 33%). Of a total of 17 glands identified surgically as hyperplastic and confirmed by pathological examination,99mTc‐sestamibi scintigraphy showed a positive image in 10, corresponding always to the larger abnormal glands (sensitivity 58.8%, higher than that observed with the other techniques). No false positive images were obtained with99mTc‐sestamibi. All the ectopic adenomas (n= 3) were identified preoperatively, which contributed significantly to the surgical approach.CONCLUSION In patients with hyperparathyroidism,99mTc‐sestamibi scintigraphy may be used as the single imaging technique as it shows a very high sensitivity and specificity in the preoperative localization of pathological parathyroid glands; the benefit of localizing parathyroid tissue prior to surgery in cases of ectopic adenomas clearly indicates that when an imaging procedure is required, this technique may be of great help in the management of hy

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02915.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Vitamin D intoxication is a relatively rare but treatable cause of hypercalcaemia. In the past this has been undertaken using corticosteroids. Previous observations have suggested that there is increased bone resorption in hypervitaminosis D. If this were to be the case, specific inhibitors of bone resorption might provide more effective treatment. We have therefore studied the mechanisms of hypercalcaemia and response to therapy in a group of patients with vitamin D intoxication.DESIGN Vitamin D metabolites were measured in six patients with vitamin D intoxication; in five of these the components of hypercalcaemia were calculated. These measurements were repeated following treatment with corticosteroids (two patients) or the bisphosphonate, pamidronate (three patients).RESULTS In each case the serum 25‐hydroxyvitamin D was grossly elevated and there was a more modest elevation in serum 1,25‐dihydroxyvitamin D. The components of hypercalcaemia suggest that there was a significant degree of bone resorption in all six patients and that this Is the major determinant of hypercaicaemia. Pamidronate treatment resulted in a brisk reduction in plasma calcium concentration. Following corticosteroids the return of calcium to normal was more delayed.CONCLUSION The hypercalcaemia of vitamin D intoxication is mediated by Increased bone resorption and bisphosphonates have a role in its managem

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02916.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE The recent advances In assisted fertilization and gamete micromanipulation techniques have enabled fertilization in some forms of azoospermia; for example, epididymal sperm aspiration in obstructive azoospermia. Therefore knowledge of the specific degree of testicular damage is of primary importance, since other clinical parameters, such as FSH plasma levels and testicular volume, do not discriminate between the different testiculopathies. in order to further Characterize the specific testicular conditions present in azoospermia, we have examined a large group of azoospermic subjects on the basts of testicular cytological analysis obtained by fine needle aspiration. DESIGN AND PATIENTS One hundred and twenty‐two infertile, azoospermic men were studied by physical examination, FSH radioimmunoassay, testicular ultrasound examination and fine needle aspiration of the testes. Thirty‐five infertile normozoospermic subjects were studied as controls.RESULTS The cytological analysis Identified five different sub‐types in azoospermic subjects: I, Sertoli cell‐only syndrome; II, hypospermatogenesis; III, spermatogonial and/or spermatocytic arrest; IV, spermatidic arrest; and V, normal germ line. The testicular volume was reduced in groups I and II, while the FSH plasma levels were Increased in groups I, II and III, suggesting a primary role of spermatids In the control of FSH secretion.CONCLUSIONS in azoospermic subjects, testicular cytological analysis permits the Identification of different sub‐types and this classification may be very important in determining therapy, particularly the choice between surgical treatment and the hypothetical use of assisted fertilization techniques by retrieval of epididymal or Intratesticular spermatozoa or s

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02917.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The diagnosis of Cushing's syndrome remains a major challenge in clinical endocrinology. Various screening tests are commonly used to support a biochemical diagnosis in the context of clinical suspicion. The aim of this study was to compare the sensitivity in the diagnosis of Cushing's syndrome of a single in‐patient sleeping midnight cortisol to a standard 48‐hour in‐patient low‐dose dexamethasone suppression test (LDDST) during the same admission.DESIGN A retrospective analysis was performed on 150 patients Investigated in our department between the years 1970 and 1994 with a confirmed diagnosis of Cushing's syndrome.PATIENTS One hundred and fifty patients with a diagnosis of Cushing's syndrome were analysed: 110 with Cushing's disease; 12 with tumours with ectopic ACTH secretion; 8 with ACTH dependent Cushing's syndrome of so far undetermined origin; 17 with cortisol secreting adrenal tumours; 3 with adrenocortical nodular hyper‐plasia. Twenty normal volunteers and nine patients with non‐endocrine conditions were also investigated as controls.MEASUREMENTS Plasma cortisol was measured by radioimmunoassay (RIA) in the 122 patients presenting after 1980, and by fluorimetry prlor to this date.RESULTS In all the control subjects the sleeping midnight cortisol was<50 nmol/l, below the lowest standard of the routine In‐house RIA. In every patient with Cushing's syndrome the sleeping midnight cortisol was detectable with a value greater than 50 nmol/l, with a range of 70–2000 nmol/l. In contrast, in three cases, all of whom had proven Cushing's disease on histology, there was uncharacteristic complete suppression of plasma cortisol to<50 nmol/l following the LDDST.CONCLUSION In this series of 150 cases, a single in‐patient sleeping midnight cortisol above 50 nmol/l had a 100% sensitivity for the diagnosis of Cushing's syndrome, clearly different from normal subjects. in contrast, the low‐dose dexamethasone suppression test had a sensitivity of 98% even when the drug was administered as an in‐patient. We recommend that a low‐dose dexamethasone suppression test should not be used alone for confirmation of Cushing's syndrome since

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02918.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE We previously reported the clinical characteristics of Graves' disease with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit, but a study of the prognosis of untreated TBII negative patients with anti‐thyroid drug medication has never been undertaken. The aim of this paper is to study the difference between negative and positive TBll Graves' disease in relation to the effect of anti‐thyroid drug treatment.PATIENTS From January 1986 to April 1991,1545 patients with untreated Graves' disease were referred to Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified. Another 83 TRAb positive patients were randomly selected from the other Graves' disease patients and served as a comparison group. Fifty‐six of the 94 patients in the TBII negative group and 52 of the 83 patients in the TBII positive group completed treatment with methimazole only.MEASUREMENTS The trial was conducted as a retrospective study with a maximum treatment period of 36 months and a follow‐up period of a further 12 months. From the original pool of patients, we classified 56 TBII negative patients into two groups according to the clinical course taken; Group A in whom TBII remained undetectable throughout methimazole treatment (9 men and 34 women, age 37.2 ± 2.2 years), and Group B who became TBII positive (4 men and 9 women, 31.2 ± 44 years). Fifty‐two TBII positive patients served as the comparison Group C (8 men and 44 women, age 38.1 ± 2.0 years).RESULTS Serum free T4 and free T3 levels in groups A and B were significantly lower before treatment than those of Group C (P<0.001). The thyroid volumes of Group A and B patients were significantly smaller than those of Group C (P<0.01). The level of TBII in Groups A and B was significantly lower than that in Group C (8.3 ± 0.7 and 8.8·1.1vs57.0 ± 28%, respectively,P<0.001). The level of thyroid stimulating antibody (TSAb) in Groups A and B was significantly lower than that in Group C (478 ± 71.0 and 761 ± 140.3vs2143 ± 280%, respectively,P<0.01), and there were no significant differences in TSAb activities between Groups A and B. The remission rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data Indicate that Group A has a good prognosis, but Group B has the same prognosis as Group C.CONCLUSION We conclude that patients In whom TSH binding inhibitor Immunoglobulins remained negative have a much better prognosis than TSH binding inhibitor immunoglobulins positive patients or those who become TSH binding inhibitor immunoglobulins positive, having been

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02919.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE It is known that growth hormone can Induce accelerated bone turnover in GH deficient people as well as healthy elderly people. In this study we examined the effect of recombinant human GH (rhGH) on bone mineral mass and bone turnover in the presence of the bone resorption inhibiting agent, pamidronate. Effects on body composition were also studied.METHODS Twenty‐one post‐menopausal osteoporotic women were treated with the bisphosphonate pamidronate during 12 months. During the Initial 6 months rhGH (0.0675 IU/kg, 3 times/week) was administered In a placebo controlled fashion (10 vs 11 patients).MEASUREMENTS Bone mineral Content (BMC) of the lumbar spine and femoral neck was measured with dual‐energy X‐ray absorptiometry and BMC of the distal and proximal forearm with single‐photon absorptiometry. Body composition was measured with bioelectrical Impedance and total body dual‐energy X‐ray absorptiometry. Serum IGF‐I and biochemical indices of bone turnover were also measured.RESULTS The group treated with rhGH showed a two to three‐fold Increase In serum IGF‐I levels. No effects on bone mineral mass were observed in the group treated with rhGH, either after the Initial 6 months of treatment with rhGH or after the total period of 12 months. In women treated with pamidronate, however, a consistent increase of about 5% at the lumbar spine and somewhat less in the distal forearm was reached from 6 months onwards. In neither group was any change observed in BMC at the femoral neck or forearm.Compared to baseline, the biochemical measurements of bone turnover showed a decrease of about 50% in the pamidronate treated group, but this effect was blunted in the group additionally treated with rhGH.The body composition measurements showed clear effects of rhGH administration: a decrease in fat mass of about 5% and an increase In lean body mass of about 3%. However, these effects disappeared after the treatment with rhGH was stopped and both fat mass and lean body mass returned to Initial values.CONCLUSIONS The present study suggests that treatment with rhGH blunted both the pamidronate induced accumulation of bone mineral mass and the reduction of biochemical markers of bone turnover. Furthermore, the positive effect of rhGH on body composition disappears completely after cessation of

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02920.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Insulin resistance increases during adolescence, and is exaggerated in patients with insulin dependent diabetes mellitus (IDDM). A relative deficiency of insulin‐like growth factor‐I (IGF‐I) may contribute to this increased insulin requirement. Two mechanisms have been proposed: (a) increased GH secretion, caused by failure of IGF feedback control, leading to increased insulin resistance and (b) lack of Insulin‐like action of the IGFs which is reinforced by high plasma levels of IGFBP‐1, an inhibitor of IGF action. The contribution of these two mechanisms to the ‘dawn phenomenon’ is assessed.DESIGN The two possible mechanisms were studied during the dawn rise of glucose in pubertal adolescent patients with IDDM. Two overnight studies were performed in each subject. Patients remained on the same insulin regimen throughout.SUBJECTS Twenty‐two diabetic adolescent subjects, aged (mean ± SEM) 14.0 ± 0.4 years, duration of IDDM 7.9 ± 0.8 years, were recruited. Pubertal status was: group 1 (breast stage 1–2; testicular volume<4–8ml) 3 male and 4 female, group 2 (breast stage 3; testicular volume 10–12 ml) 0 male 4 female, group 3 (breast stage 4–5; testicular volume 15–25 ml) 4 male and 7 female. Height standard deviation score (mean ± SD) (‐0.02 ± 099) and dally insulin dose (50.4 ± 3.1 U/day) did not change between studies. There were no differences in HbA1 (study A 11.26 ± 0.45%, study B 11.09 ± 0.42%).METHODS The subjects were admitted for the two studies 0.3 ± 0.03 years apart. Blood samples were taken via an indwelling cannula every 20 minutes between 1900 and 0700 h.MEASUREMENTS GH was assayed every 20 minutes, IGFBP‐1, glucose and free Insulin every hour and lGF‐I at 0700h. GH, IGFBP‐1, IGF‐I and free insulin were measured by radioimmunoassay. IGFBPs were also analysed by Western ligand blotting techniques. GH profiles were analysed by Pulsar and results compared by paired Student's t‐test. The relations between the dawn rise In glucose and the changes in IGFBP‐1, GH and free insulin were examined by multiple linear regression analysis.RESULTS Serum IGFBP‐1 levels rose overnight In the two studies (study A, from 9·1 at 2200 to 59 ± 9μg/l at 0700 h; study B, from 10±1 at 2100 to 64 ± 14μg/l at 0700h) whilst insulin levels fell from 47 ± 5 at 2200 to 16 ± 2mU/l at 0700 h (study A) and from 45·5 at 2000 to 14 ± 2mU/l at 0700 h (study B). Glucose levels fell from 16.0 ± 1.0 to 9.3 ± 0.9 mmol/l at 0400h, and then rose to 11.9 ± 1.1 mmol/l at 0700 h during study A, and from 13.4 ± 1.3 to 10.1 ± 1.1 mmol/l at 0400 h and then rose to 13.5 ± 1.0 mmol/l at 0700 h during study B. There were no differences in GH secretion between studies (mean GH levels (mean ± SD) (study A, 15.7 ± 6.6 mU/I; study B, 16.2 ± 7.1 mU/l; correlation within subjects between studiesr= 0.77,P<0.001), sum of GH peaks (study A, 189.9 ± 903 mU/l; study B, 185.8 ±100.2 mU/l;r= 0.57,P= 0.006)). Mean GH levels varied with pubertal stage (group 1,12.1 ± 1.5 mU/l; group 2, 23.3 ± 2.1 mU/I; group 3, 15.3 ± 1.2mU/I). Serum IGF‐l levels were not different (study A, 203 ± 12 μg/l; study B, 218 ± 13 μg/l).REGRESSION ANALYSIS The change In plasma glucose between 0200 and 0700 h In both studies related to free insulin, IGFBP‐1 and the sum of the GH levels over the preceding hour (log glucose =7.87 + 5.32 log IGFBP‐1 (P= 0.0001) −5.05 log free insulin (P= 0.0001)‐1.44 log GH (P= 0.004);R2= 72%). Mean overnight GH levels did not predict the morning rise In plasma glucose.CONCLUSION The morning rise of IGFBP‐1 and plasma glucose appear to be related in this group of subjects with IDDM and this was a consistent finding In the two studies. This relation was additive to the effect of Insulin deficiency. No positive relation was noted between GH secretion and glucose levels. These findings support the hypothesis that the increased GH secretion In IDDM Is a marker of IGF‐I deficiency rather than a direct causal factor in the increase In insulin resistance. The IGFs may therefore have a direct role In glucose homeostasis via the ‘free’ fract

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02921.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVE High doses of flutamide, which is the only antiandrogen that specifically blocks the androgen receptor, have recently been used with good clinical results in women with hirsutism. Since regression of hair growth requires long‐term therapy, clinical and economic considerations are important. The use of the lowest efficacious dosage could reduce costs. This study was undertaken to compare safety and efficacy of a low dose of flutamide (125 mg twice daily) alone and in combination with a triphasic oral contraceptive (OC) in women with idiopathic hirsutism.PATIENTS Flutamide was administered orally in a low dose of 125mg twice daily for 12 months alone in women with no risk of pregnancy or during the use of an oral contraceptive.MEASUREMENTS Women were seen every 3 months and were evaluated for hirsutism score, hormone and lipid measurements.DESIGN The study, which was conducted as a prospective open trial, was proposed to patients with idiopathic hirsutism, that is, with serum androgen levels in normal range and LH/FSH ratio less than 2.RESULTS A statistically significant decrease in hirsutism score as compared to baseline was observed after only 3 months with either treatment, flutamlde alone (16.9 ± 1.6vs14.2 ± 1.7,P<0.0001) or the combination of flutamide with OC (15.6 ± 0.8vs11.9 ± 0.8,P<0.001). Three months after cessation of treatment a statistically significant decrease from baseline was observed in the two groups. Nevertheless, at 6 months post‐treatment this decrease was still Significant only in the group who took flutamlde in Combination with an oral Contraceptive. Flutamide alone does not appear to modify the levels of lipoproteins. The association of flutamide with a triphasic formulation significantly Increased the HDL‐C levels. CONCLUSIONS This study shows beneficial effects of a low dose of flutamide in women with idiopathic hirsutism. The addition of an oral contraceptive is judicious to prevent pregnancy and reduce recurrence of hirsutism after cessation of flutamide. Peripheral androgenic blockage does not modify lipid profiles and it might reduce the negative effect of oral contraceptive on HDL‐C levels. The addition of electrolysis delays the recurrence of hirsutism after cessation o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb02922.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY