ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01815.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryEndocrine autoimmunity is known to be characterized by the presence of specific autoantibodies and from the histopathological point of view by lymphocytic inflitration in the target tissue. The presence of mononuclear cell infiltrates is the pathological hallmark of most endocrine diseases characterized by an autoimmune process directed against antigens expressed on endocrine cells. Infiltrating cells can usually be detected by biopsy or by using other, non‐invasive, techniques. However, in endocrine tissue such as the islets of Langerhans and the adrenal glands it is difficult to perform biopsies and diagnosis of the autoimmune process is dependent mainly upon detection of specific autoantibodies. A crucial aspect of endocrine autoimmunity and of all processes of organ specific autoimmunity is why and how lymphocytes migrate from primary lymphoid tissue to their specific targets. This occurs mainly through contact with specific adhesion molecules which enable lymphocytes to adhere to the endothelial vessels. In close proximity to the target tissue. In this review we discuss the homing of peripheral mononuclear cells into target endocrine tissues and the mediating role of adhesion molecule

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01816.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01817.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE By using vaginal endosonography, ovarian stromal hypertrophy has been shown to be a strong diagnostic feature of polycystic ovarian syndrome and related states. However, this sign is difficult to quantify and to correlate with other findings because of its subjectivity. We have evaluated the use of computer assisted analysis of ultrasound scans to provide more objective measurements of ovarian structure and size.DESIGN We used a computer assisted method for the reading of ultrasound scans. It allowed selective calculation of the stromal area by subtraction of the cyst area from the total ovarian area on a longitudinal ovarian section.PATIENTS A consecutive series of 57 patients with hyper‐androgenism (group 1), 17 patients with hypothalamic anovulation (group 2) and 20 normal women (group 3).RESULTS By computerized measure, 75% patients from group 1 had a bilateral stromal area above the mean +2 SD (700 mm2) of women from group 3. All patients from group 2 were below this threshold. Serum LH level was above the normal range in 45% patients from group 1. The stromal area correlated positively with the serum A4‐androstenedione (r= 047,P<0.005) and 17α‐hydroxy‐progesterone (r= 039,P<0.005) levels, exclusively in group 1. It did not correlate with the basal serum testosterone, LH or Insulin levels. The cyst area did not correlate with any hormonal parameter.CONCLUSION Ovarian stromal hypertrophy is a frequent and specific feature of hyperandrogenism. It correlates with the ovarian androgenic dysfunction. Its presence is not always linked with elevated serum Immunoreactive LH levels. Further data are needed to elucidate the role of insulin and ovarian growth

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01818.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE Critical Illness has been associated with decreased LH secretion and lowering of testosterone. Dopamine is often used for vasoactive support in these patients. We therefore aimed to Investigate LH secretion during severe illness and particularly the effect exerted by dopamine on LH in such patients.PATIENTS AND DESIGN In a randomized, controlled study of critically 111 adult male polytrauma patients (n= 8), we evaluated the effect of prolonged (83‐298 hours) dopamine infusion (5μg/kg/mln I.v.) on the dynamics of LH secretion and on serum testosterone Concentrations. The effect of brief (15‐21 hours) dopamine administration was documented in an additional randomized, controlled, crossover study involving 6 patients.MEASUREMENTS Serum LH concentrations were measured by IRMA. The LH profiles, obtained by blood sampling every 20 minutes for 9 hours during two consecutive nights, were examined by deconvolution analysis. Serum testosterone concentrations were measured by RIA once per study night. RESULTS We found that before dopamine initiation and within 24 hours of dopamine withdrawal, the mean serum LH concentrations, the LH secretory amplitude, the amount of LH secreted per burst, the mean LH secretion rate and the number of LH pulses were higher than during dopamine infusion, being increased by a median of 161 % (P= 0·006), 98% (P= 0·03), 106% (P= 0·03). 164% (P= 0·01) and 25% (P= 0·008) respectively. However, without dopamine administration the amplitude and mass of the LH secretory bursts still appeared to be low, whereas the pulse frequency remained elevated. After dopamine withdrawal, LH secretion increased significantly within 3 hours. Serum testosterone levels were very low and dopamine infusion appeared not to affect them within 24 hours.CONCLUSION We documented decreased LH secretory pulse amplitude and mass with Increased pulse frequency, as well as very low serum testosterone concentrations in critically ill men. Dopamine Infusion further suppressed LH release by decreasing secretory burst amplitude, mass and frequency, possibly through an inhibitory action at both the pituitary and the hypothala

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01819.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE Recent studies have suggested that androgen secretion by ovarian virllizing tumours may be gonadotrophin dependent. The aim of this study was to investigate the suppressive effect of GnRH agonist administration on androgen secretion. In women with such tumours.DESIGN AND PATIENTS A single 1.m. Injection Of D‐Trp‐6‐GnRH (GnRHa), 3·75 mg, was given to five unrelated patients referred for clinical symptoms of virilization with plasma testosterone (T) levels greater than 7 nmol/l but with normal dehydroeplandrosterone sulphate (DHEAS) levels. Diagnoses of adrenal tumour or a non‐classical 21‐hydroxylase deficiency were screened for by the dexamethasone suppression test, ACTH stimulation test and adrenal CT scanning, and were ruled out in all patients. The one premenopausal patient received cyproterone acetate in a dose of 50 mg twice dally for 3 weeks, starting 1 week before GnRHa administration.MEASUREMENT Testosterone, androstenedione (A), DHEAS, 17‐hydroxyprogesterone (OHP), LH and FSH plasma concentrations were measured by radioimmunoassay of blood samples taken before and 3 weeks after GnRHa.RESULTS In each patient, GnRHa suppressed gonadotrophin levels and reduced T and A to the range for normal control women. With these results, and because accurate localization of an ovarian androgen secreting tumour could not be achieved by pelvic ultrasonography and CT scanning, exploratory laparotomy was undertaken. A Sertoll‐Leydig cell tumour was found in the premenopausal patient, and granulosa cell tumour, hllus cell tumour and two hyperthecoses in the four post‐menopausal patients. After bilateral ovarlectomy and hysterectomy in the post‐menopausal woman and after unilateral ovarlectomy in the premenopausal women, androgen levels were normalized.CONCLUSIONS In virllized women, the findings of Increased serum testosterone with normal gonadotrophin levels and GnRHa suppression of gonadotrophins leading to normalization of testosterone levels, suggest that various ovarlan androgen‐secreting tumours, as well as hyperthecosis, are not autonomous but apparently depend upon continuous gonad

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01820.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim of the study was to test the hypothesis that clinically unaffected female carriers of X‐linked Kallmann's syndrome have an olfactory defect.DESIGN Assessment of the olfactory threshold to seven standard odorants, each at a concentration of 1‐10‐8mol/1.PATIENTS Five families with X‐linked Kallmann's syndrome (KS) were tested, containing 19 males with KS, and 9 female carriers. Related but unaffected males (n= 8) were used as a control group, and in addition seven patients with Turner's syndrome (XO) were assessed.MEASUREMENTS The olfactory threshold was taken as the lowest concentration at which each odorant was clearly distinguished from control (liquid paraffin). The threshold for each odorant was compared between the subject groups using the non‐parametric Mann‐Whitney test.RESULTS All patients with KS were anosmic to all odorants. The female carriers had hyposmla, with a significant reduction in the olfactory threshold to putrid, peppermint, floral and pungent odorants compared to control subjects, and to peppermint, floral and pungent odorants compared to subjects with Turner's syndrome. The latter had olfactory thresholds which were statistically identical with the control group.CONCLUSIONS Obligate female carriers of X‐linked Kallmann's syndrome are hyposmic compared to control subjects. The overlap between the two groups, however, makes olfactory testing unreliable as a di

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01821.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE Hereditary vitamin D resistant rickets (HVDRR) has been shown to be due to mutations in the gene encoding the vitamin D receptor (VDR). In two patients with the characteristic phenotype we have investigated the functional defect and sequenced the VDR cDNA. We report two new mutations in the DNA binding domain of the VDR gene and we have used the crystal‐lographic structure of the glucocorticold and oeltrogen receptors (GR and ER respectively) as models to explain the stereochemical consequences of these mutations.DESIGN Patient and control cell lines prepared from skin fibroblasts were used to measure binding of 1,25dlhydroxyvltamln D3(1,25(OH)2D3) and functional responses to this hormone. These cells were also used to Isolate VDR mRNA from which cDNA was prepared and sequenced. VDR cDNA from affected and control patlents was also transfected into receptor defective cells to analyse further functional responses to 1,25(OH)2D3. Computer analysis of mutations in the VDR gene was carried out using the glucocorticold and oestrogen receptors as model systems.PATIENTS Two patients with HVDRR from unrelated families.MEASUREMENTS Cytosollc binding and nuclear association of 1,25(OH)2D3were determined in control and affected patients, and functional response to 1,25(OH)2D3was assessed by measurement of 2bhydroxyvltamln D‐24‐hydroxylase activity (24‐hydroxylase). VDR cDNA was sequenced and transfected into VDR‐deficient CV‐1 cells for further analysis of functional response to 1,25(OH)2D3following cotransfection with a chloramphenicol acetyltransferase (CAT) reporter plasmid.RESULTS Cells from HVDRR patients I and II showed detectable numbers of VDR with normal hormone binding. However, unlike controls, the HVDRR cells did not show induction of 24‐hydroxylase activity following treatment with 1,25(OH)2D3. Sequencing of cDNA revealed single mutations, in patient I (Phe44 → IIe) and in patient II (Lys42 → Glu). Both these residues are conserved in the steroid/thyroid hormone receptor superfamily and stereochemical analysis has been used to deduce the importance of these amino acids and the deleterious effect of these and other mutations in the DNA‐binding domain of the VDR.CONCLUSIONS Two new mutations in the vitamin D receptor which cause hereditary vitamin D resistant rickets have been described and using molecular modelling we have been able to analyse the genesis of this inherited disease at the level

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01822.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE Hypercaicaemia of malignancy (HM) is a common metabolic complication associated with cancer. The hypocaicaemic effects of medications used to reduce serum calcium levels in HM are short lived and relapse in hypercaicaemia is not uncommon. Pamidronate is one of the most commonly used bisphosphonates in the treatment of HIM but there are no specific guidelines for the frequency of use of this drug in recurrent hypercalcaemia. This study was conducted to assess the optimum frequency of pamidronate therapy necessary to maintain normocalcaemia in patients with HM.DESIGN AND PATIENTS Thirty‐four patients With HM were randomly allocated into two groups and treated with intravenous pamidronate administered every 14th or 21st day for 16 weeks (n= 17 each group). Serum calcium and urinary hydroxyproline creatinine ratio were measured at weekly intervals.RESULTS The calcium‐lowering effect of pamidronate was apparent by 48 hours and normocalcaemia was maintained for an average of 15 days. When the drug was administered every 3 weeks, hypercalcaemia and associated symptoms developed in 50% of patients (22 separate episodes) during the 3rd week, before the next dose of pamidronate. The incidence of symptomatic hypercalcaemia was significantly decreased (10%, 8 separate episodes,P<0·01) and survival was improved (P<0·05) in patients who received pamidronate every 2nd week, thereby minimizing the unpleasant and potentially dangerous effects of hypercalcaemia.CONCLUSIONS Intravenous pamidronate 60 mg/dose, administered every two weeks, can maintain normocalcaemia in the vast malority of patients with hypercalcaemia of malig

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01823.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE The few published prospective studies suggest a strong association of colonic tumours with acromegaly, but include small numbers of patients. In addition, the upper gastrointestinal tract of these patients has never been prospectively studied. The aim of the present study was to investigate the incidence of gastric and colonic tumours in a large cohort of acromegalic patients.DESIGN Acromegalic patients consecutively admitted to an Endocrinology Department for diagnosls and follow‐up, were submitted to gastroscopy and colonoscopy, to identify those harbouring gastrointestinal tumours.PATIENTS Over a 5‐year period, 54 out of 61 patients (78% with active disease) received colonoscopy and 42 out of 61 gastroscopy. No patient had a past history of gastrointestinal malignancy.MEASUREMENTS All polypoid lesion8 found at colonoscopy and gastroscopy were separately recorded and biopsled.RESULTS No case of gastrointestinal cancer or gastric polyp was discovered. Nineteen patients (35%) had 1‐8 colonic polyps, including 5 (9·3%) with adenomas. When compared to patients with a normal colon, those with polyps were significantly older (44·±14· vs 52· f 10·9 years,P= 0·47), but the duration of acromegaly (10·±8· vs 10·±7· years,P= 0·9) and the number of patients with active disease were similar in both groups.CONCLUSIONS Acromegalic patients do not have an increased incidence of gastric tumours. The observed significant variation in the prevalence of colonic adenomas (9‐35%,P= 0·03) and cancer (0‐15%,P= 0·017), between our patients and those of the published prospective studies with similar demographic characteristics, suggest that environmental and hereditary factors may be more important than t

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb01824.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY