摘要:

SummaryDESIGNThere are conflicting data on hypothalamic‐pituitary‐adrenal (HPA) axis function in women with polycystic ovary syndrome (PCOS). We have evaluated the HPA axis responses to naloxone in patients with PCOS compared to control subjects.PATIENTSTwenty PCOS patients and 10 control women participated in the study.MEASUREMENTSOn days 5–6 Of a spontaneous or progestin induced cycle each patient received an intravenous bolus (5 mg) of naloxone (time 0 min), followed by a 2‐mg naloxone infusion In 100 ml of 0.9% saline over one hour. Samples were collected at −30, 0, 15, 30, 60, 90 and 120 minutes. ACTH and cortisol levels were measured in all plasma samples.RESULTSPCOS patients showed significantly greater response than controls to naloxone of ACTH (peak value 261vs172% of basal value) and cortisol (peak value 237 vs 165% of basal value); also, ACTH and cortisol incremental areas were higher In PCOS patients (P<0.05 andP<0.04 respectively).The cortisol/ACTH ratio of AUCs percentage increase was found to be near unity for all patients without significant difference between PCOS and control groups, suggesting a direct correspondence between ACTH circulating levels and adrenal cortisol production.CONCLUSIONSPolycystic ovary syndrome patients showed a hypothalamic‐pituitary‐adrenal axis hyper‐responsiveness to naloxone infusion compared with control subjects. These data support the hypothesis that this disturbance could be ce

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02062.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryOBJECTIVEThe expression and Synthesis of IGF‐I and IGFBP‐3 have been shown to be regulated by hormones and nutrition. We study the effects of malnutrition and iodine deficiency on these growth factors and the height attainment of a group of children.DESIGNWe measured serum IGF‐I and IGFBP‐3 levels in a group of Malaysian aborigine children from three jungle settlements; Sinderut and Pos Lanai are known for iodine deficiency and endemic goitre, and Gombak is an iodine replete area with better socioeconomic status.PATIENTSA total of 246 children were studied, 188 In the age group 4–10 years and 88 in the age group 11–15 years.MEASUREMENTSAll children were assessed anthropo‐metrically and height standard deviation score (SDS) were calculated using the CDC Anthropometric Software package. Malnutrition was confirmed clinically and according to the WHO definition of malnutrition. IGF‐I and IGFBP‐3 were determined by radioimmunoassay, and T4 and TSH by immunoradiometric assay.RESULTSBased on the height SDS, Sinderut and Pos Lanai children were significantly more malnourished and stunted than the Gombak childrenP= 0 0001). T4 levels were significantly lower (P= 0.0001) amongst the 4–10‐years old Sinderut (87 ± 2nmol/l) than In Pos Lanai (101 ± 3nmol/l) or Gombak (123 ± 3 nmol/l) children. Similar findings were also seen in the older children; mean T4 levels of those from Sinderut and Pos Lanai (83 ± 3 and 88 ± 4 nmol/l respectively), were low (P= 0.0001) compared to Gombak (118 ± 3 nmol/l). Conversely, TSH levels in both age groups of Slnderut children were significantly elevated (P= 0.0001) (3.5 ± 0.2 and 3.9 ± 0.3mU/l respectively) compared to age‐matched groups from Pos Lanai (2.1 ± 0.1 and 2.2 ± 0.2 mU/l respectively) and Gombak (1.5 ± 0.1 and 1.5 f 0.2mU/l respectively). IGF‐I and IGFBP‐3 correlated significantly with the height SDS of the children, in both the 4–10 (r= 0.400,P= 0 0001 andr= 0.365,P= 0.0001 respectively) and 11–15 years age groups (r= 0.324,P= 0.002 andr =0.533,P= 0.0001 respectively). Correlation between IGFBP‐3 and T4 levels was more significant In the younger children (r= 0.412,P= 0.0001). Association between IGF‐I and T4 levels was significant only in the 4–10 years age group (i = 0 237,P= 0.001). CONCLUSIONS Varying duration and degree of exposure to malnutrition and Iodine deficiency resulted in different mean levels of T4, TSH, IGF‐I and IGFBP‐3 in the three areas. The strong positive associations between IGF‐I and IGFBP‐3 levels and height SDS suggest that these biochemical measurements are Indeed useful indicators of growth and nutritional status in children. The significant correlations between T4 and IGFBP‐3 and IGF‐I suggests the Importance of thyroid hormones in regulating the synthesis of these growth factors. The age‐related Increase of these growth factors even amongst mainourlshed, iodine deficient children implies that age‐matched reference

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02063.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryOBJECTIVEHereditary vitamin D resistant rickets (HVDRR) is an autosomal recessive disorder resulting in target organ resistance to the actions of 1,25‐dihydroxyvitamin D3(1,25(OH)2D3). In many cases, this disorder has been shown to be due to mutations in the gene encoding vitamin D receptors (VDR). In a patient with characteristic features of this disorder, we investigated the functional defect and sequenced the coding region of the gene for mutations.DESIGNSkin fibroblasts from patient and control were used to measure binding of 1,25(OH)2D3and functional responses to the hormone. These cells were also used to prepare RNA from which cDNA was prepared and sequenced. Furthermore, genomic DNA was prepared from the fibroblasts and the intronlexon boundarles sequenced.PATIENTA child with classic features of HVDRR with alopecia diagnosed as having rickets due to resistance to 1,25(OH)2D3.MEASUREMENTSNuclear association of 1,25(OH)2D3was determined in patient and control cells and the functional response to 1,25(OH)2D3was assessed by measurement of 25‐hydroxyvitamln D‐24‐hydroxylase(24‐hydroxylase) activity. VDR cDNA and genomic DNA prepared from patient and control cells were sequenced.RESULTSCells from the patient with HVDRR had undetectable amounts of VDR compared to control cells and did not show induction of 24‐hydroxylase activity following treatment with 1,25(OH), D3. Sequencing of the VDR coding region after RT‐PCR of RNA revealed an absence of exon 4 in patient RNA which was not due to a deletion in genomic DNA but was caused by exon skipping during RNA processing. In addition, the deletion of exon 4 sequences from RNA leads to a frameshift in translation resulting in a premature stop codon. Amplification of genomic DNA around the intron/exon boundary of exon 4 revealed a point mutation in the 5’donor splice site of intron 4.CONCLUSIONIn this study, we have identified a novel mutation in the gene for vitamin D receptors in a patient with the Characteristic phenotype of hereditary vitamin D resistant rickets. The mutation at the + 5 position in intron 4 is most likely to cause skipping of exon 4

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02064.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryBACKGROUND AND OBJECTIVESThe molecular pathogenesis of phaeochromocytoma has not yet been fully established. The p16 turnour suppressor gene is often inactivated in a wide variety of primary human malignancies, including tumours of ectodermal origin. We have therefore examined the status of the p16 gene in a series of phaeochromocytomas.DESIGNWe studied tumour and constitutive DNA from 26 phaeochromocytoma patients. Twenty‐two cases were of sporadic tumours whereas four patients had a hereditary form of the disease. Four tumours were malignant. We performed a semiquantitative multiplex PCR in which the p16 gene was coamplified with an unrelated sequence as an internal control. Standards were constructed by mixing DNA from cell lines with a known p16 status to simulate various degrees of p16 loss. Deletion of the p16 gene was determined by densitometry, measuring the ratio of intensity of the two resulting bands as an indication of the relative abundance of the two templates in the sample.RESULTSNo homozygous deletion of the p16 tumour suppressor gene was found in any of the phaeochromocytoma samples.CONCLUSIONSWe have demonstrated that the p16 gene is not deleted in sporadic, hereditary, malignant or benign forms of phaeochromocytomas, and therefore probably does not play a role in the pathogenesis of this tumour. However, because of the small number of malignant cases analysed, we cannot exclude a low frequency of p16 deletions in this subset of tumour

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02065.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryOBJECTIVEAdrenal insufficiency (Al) is a well known complication of AIDS. However, the clinical and biochemical features of Al in HIV infected patients have not been extensively studied.DESIGNA restrospective clinical study.PATIENTSWe reviewed clinical records of 74 AIDS patients with clinical and/or biochemical indications of Al who underwent Synacthen testing in order to determine adrenocortical function during a 5‐year period.MEASUREMENTSAI was diagnosed when Cortisol levels failed to rise above 496 nmol/l at any time during the test. Cortisol was measured by RIA.RESULTSSixteen patients (22%) were diagnosed with Al. Most were young males and all of them had a known risk factor, principally I.v. drug users. The main complaint was fatigue. Hyponatraemia or hyperkalaemia were uncommon. All of them were severely immuno‐suppressed, with AIDS‐defining conditions from at least 6 months before the diagnosis of Al, and had been diagnosed with at least one disease that has been reported to produce Al in AIDS patients. Survival was poor. Thirteen of these patients (81%) died within 6 months. Basal cortisol levels were lower than 275 nmol/l in 75% of patients with Al but in only 2% of the group of 58 patients who had normal adrenal responses to Synacthen.CONCLUSIONSAdrenal insufficiency features in AIDS patients with advanced disease, without specific findings and with a history of previous opportunistic diseases. Basal cortisol values at 0830 h lower than 275 nmol/l are highly suggestive of adrenal insufficiency in patients with

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02066.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryWe describe a female patient who was diagnosed and treated at birth for a classic form of salt‐losing congenital adrenal hyperplasia. At 17 years of age, against medical advice, she discontinued both mineralocorticoid and glucocorticoid replacement with no resulting clinical symptoms other than the occurrence of amenorrhoea. Steroid metabolites revealed significant abnormalities of the renin‐angiotensin‐aldosterone axis, as well as of pituitary‐adrenal function. Analysis of our patient's DNA showed only one deleterious CYP21 mutation, an intron 2 base pair change activating a cryptic splice site. We speculate that expression of this patlent's CYP21 genes may be altered by the effects of ageing or by changes in the steroid

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02067.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryCardiovascular changes associated with Graves' disease are generally considered to be secondary to the increased levels Of thyroid hormone. We describe a case of Graves' disease in a 25‐year‐old man, who developed cardiomyopathy with severe heart failure. Pathological examination of the myocardial biopsies showed fibroblast infiltration and degenerative changes. After the cardiomyopathy subsided the patient developed a goitre and signs of hyperthyroidism, followed by Graves' ophthalmopathy, which was treated successfully with a combination of high‐dose corticosterolds and orbital radiotherapy. These findings suggested a common pathogenesis for the cardiomyopathy and ophthalmopathy, and prompted us to investigate the expression of TSH receptor (TSH‐R) in human heart. TSH‐R mRNA was identified in human heart using the reverse transcriptase‐polymerase chain reaction (RT‐PCR) and DNA sequencing. Taken together, these data suggest that autoimmunity against the TSH‐R mlght contribute to both the cardiomyopathy and ophthalmopathy in similar cases of

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02068.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SummaryMultiple endocrine neoplasia type one (MEN 1) is characterized by tumours of the parathyroid glands, pancreatic islet cells and the anterior pituitary and follows an autosomal dominant pattern of inheritance. We report identical twins born to a family known to have the MEN 1 syndrome. The twins were identical until puberty. The first twin underwent puberty normally; the second, however, suffered an early pubertal arrest and was subsequently found to have a prolactinoma. Both were also subsequently shown to have primary hyperparathyroldism. Genetic studies have since confirmed the twins identical for the affected haplotype and show that this is inherited from the father who also has MEN 1. The gene for MEN 1 has now been localized to the long arm of chromosome 11. The current hypothesis is that expression of the syndrome involves two separate genetic mutations. The first mutation is inherited and thus present in all cells but the tumour manifests itself in the endocrine tissue only after a second mutation that represents ellmination of the normal allele. In the case described the twins are proven genetically identical. The marked phenotypic difference between the two must, by inference, represent a second somatic mutation and is further supportive evidence of the two‐mutation model of tumour expressio

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02069.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02070.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1996.tb02073.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY