ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02462.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.tb02463.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVECytoplasmic autoantibodies to vasopressin cells (AVP) have been detected in patients with idiopathic central diabetes insipidus and only in one patient with endocrine autoimmune diseases without clinical diabetes insipidus. The aim of this study was to look for AVP cell antibodies (AVP‐cell‐Ab) in human sera of a large population of autoimmune endocrine disease patients without diabetes insipidus and to test whether an occurrence of these antibodies in some patients can be associated with partial impairment of posterior pituitary function.MEASUREMENTSera from 410 patients (310 females, 100 males, age range 10–46 years) with autoimmune endocrine disorders (260 with thyroid autoimmune disease, and 150 with insulin dependent diabetes mellitus) without clinical diabetes insipidus, and from 100 normal subjects, were investigated for hypothalamic autoantibodies by an indirect immunofluorescence method. Positive sera were subsequently tested with specific rabbit anti AVP serum. RESULTS None of controls, but five out of 410 patients (1–2%) were AVP‐cell‐Ab positive. All positive and nine negative from the 410 screened patients were tested for posterior pituitary function. Two out of five AVP‐cell‐Ab positive patients showed partial diabetes Insipidus.CONCLUSIONAVP cell antibodies can be shown in some patients with endocrine autoimmune disease without diabetes insipidus and can sometimes be associated with findings of partial posterior pituitary dysfunction. This suggests that clinical diabetes insipidus could be preceded by a long subclinical period characterized only by the occurrence of AVP‐cell‐Ab in the sera associated or followed by alterations in functional tests. Longitudinal studies are needed to conf

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02464.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVESince maternal smoking causes fetal circulatory abnormalities, as well as disturbances of the maternal endocrine equilibrium, we measured the PRL, hGH and insulin‐like growth factor‐l (IGF‐I) concentrations in the cord and venous blood of neonates of smoking mothers to determine whether or not the tobacco smoke affects the endocrine status of the neonate.DESIGNThe above hormones were measured in the cord blood of the newborns of both smoking and non‐smoking mothers. Also, PRL and hGH were determined at 24 and 72 hours after birth in newborns of both groups.PATIENTSFifty‐three newborns of smoking and 47 newborns of non‐smoking mothers were investigated. Seventeen of the newborns of the smoking and 21 of the nonsmoking mothers were preterm. The remainder were full‐term.MEASUREMENTSPRL was measured with a solid‐phase immunoradiometric assay, hGH with a solid‐phase two‐site immunoradiometric assay and IGF‐I with a solid‐phase radioimmunoassay after extraction with acid‐etha‐nol.RESULTSThe median value of PRL in the 17 preterm newborns of smoking mothers was 4941 mU/l (range 1322‐7230), whereas in the 21 preterm newborns of nonsmoking mothers it was 2013 mU/l (range 243‐4740) (P = 0 0002). The median hGH value in the above subjects was 1020 mU/l (range 35 2‐208 4) and 59 8 mU/l (range 11 6‐134‐2), respectively (P = 0 0039). The median IGF‐I was 580 7 U/l (range 253 2‐4851 1) and 530 6 U/l (range 239 6‐3591 5), respectively (P = 0 429). In the 36 full‐term newborns of smoking mothers the median PRL value was 5171 mU/l (range 2074‐7530), whereas in the 26 full‐term newborns of non‐smoking mothers it was 5081 (range 244‐6540) (P = 0 048). The median hGH was 69 6 mU/l (range 42 3‐280 0) and 32 2 mU/l (range 6 2‐200 0), respectively (P = 0 0031). Also, the median IGF‐I value was 926 3 U/l (range 348 5‐5344 7) and 462 1 U/l (range 250 2‐1578 7), respectively (P = 00024). On the 3rd day the PRL in the preterm neonates of both smoking and non‐smoking mothers showed the same 16‐5% drop, and thus the difference between the groups was maintained. A similar reduction in the hormone levels was observed in the full term neonates.CONCLUSIONSThe findings indicate that the maternal tobacco‐smoking causes disturbances of the endocrine status of the fetus, as shown by the increased levels of PRL, hGH and IGF‐I, whic

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02465.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryAsingle administration of dexamethasone causes both an early stimulatory and a late inhibitory effect on GH secretion in normal subjects.OBJECTIVEWe investigated the effects of a single administration of dexamethasone on basal and GH‐releasing hormone‐stimulated GH secretion in eight patients with active acromegaly.DESIGNOn three different days the patients received 4 mg i.v. dexamethasone, 1μg/kg body weight GH‐releasing hormone 1‐29, or matched placebos in different order.PATIENTSEight subjects with active acromegaly, five of whom had not been treated previously, while the other three had received octreotide therapy which was stopped at least 7 days before testing.MEASUREMENTSSerum GH levels were measured in duplicate by a commercially available RIA kit.RESULTSDexamethasone administration caused a significant decline of mean ± SE GH levels from 51.8 ± 13.8 to 30.0 ± 9.2 mU/l at 180 minutes, that was not influenced by placebo administration at 180 minutes. On the contrary, when GH‐releasing hormone substituted placebo administration, GH levels increased from 34.0 ± 9.8 mU/l at 180 minutes to 56.0 ± 15.6 mU/l at 195 minutes. The GH increase was higher when GH‐releasing hormone was given without dexamethasone pretreatment (from 52.4 ± 13.0 mU/l at 180 minutes to 86.4 ± 25.4 mU/l at 195 minutes). Analysis of the GH area under the curve confirmed the significant inhibition of GH secretion after dexamethasone administration and the significant reduction of the GH response to GH‐releasing hormone in the study with dexamethasone pretreatment.CONCLUSIONSAt variance with data in normal subjects, acute i.v. administration of dexamethasone inhibits basal GH secretion and partially suppresses the GH response to GH‐releasing hormone in acromegaly. Both alterations in the regulatory mechanism of adenomatous cells and perturbations of hypothalamic regulatory influences, induced by the state of chronic GH hypersecretion, are likely explanations of the different re

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02466.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEA new long‐acting injectable form of bromocriptine has become available for long‐term treatment of hyperprolactinaemic patients. The objective of this study was to compare efficacy and tolerability of injectable and oral forms of bromocriptine.DESIGNA double‐blind randomized study. All patients received either one injection of bromocriptine 50 mg intramuscularly and placebo tablets for 28 days (Group A) or one placebo injection and oral bromocriptine 7 5 mg daily for 28 days (Group B).PATIENTSTwenty‐three (12 patients for Group A and 11 patients for Group B) hyperprolactinaemia patients with (19 patients) or without (4 patients) CT/MRI evidence of tumour were studied.MEASUREMENTSPlasma PRL levels and serum bromocriptine levels were assessed during a follow‐up of 42 days. MRI and/or CT were evaluated before and 28 days after the beginning of the study.RESULTSAll patients had significant reductions of PRL levels from 1000 h and 1100 h of day 1 to 2000 h of day 35. Normoprolactinaemia was shown in eight patients of Group A and six of Group B on days 1‐28. Normal PRL levels were still present in five patients of Group A and in one patient of Group B on day 35; only three patients of Group A had normoprolactinaemia on day 42. A significantly greater decrease in Group A in comparison with Group B was shown at 1200 h on day 1 and at all times as a percentage decrease from basal levels. Significantly higher levels of bromocriptine were shown in Group A at all timepoints studied. No difference was shown in tolerability and incidence of side‐effects.CONCLUSIONOur data show that injectable bromocriptine more frequently induced a prolonged normoprolactinaemia than did the oral drug. Moreover, bromocriptine levels released during injectable bromocriptine were significantly higher than during oral bromocriptine. On the other hand no difference was shown in the tolerability of bromocriptine according to the route of a

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02467.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVE ACTHis secreted by the pituitary following processing of larger molecular weight precursors, proopiomelanocortin and pro‐ACTH. Ectopic ACTH syndrome refers to the secretion of ACTH by non‐pituitary tumours, but the predominant circulating form of proopiomelano‐cortin‐related peptides remains unclear.PATIENTSFifteen patients with ectopic ACTH syndrome were compared to 20 patients with pituitary‐dependent Cushing's syndrome, 22 patients with small cell lung carcinoma but no evidence of Cushing's syndrome, and 25 controls.DESIGNAND MEASUREMENTS Measurement of plasma ACTH and ACTH precursors using specific monoclonal‐based immunoradiometric assays at 0900 h and, in five patients with ectopic ACTH syndrome, at 15‐minute intervals for 6‐24 hours.RESULTSACTH precursors were grossly elevated in patients with ectopic ACTH syndrome (median 2194, range 139‐18000 pmoI/I) compared to patients with Cushing's disease (median 33, 8‐73 pmoI/I,P<0 001), patients with small cell lung carcinomas (38, 8‐117 pmoI/I,P<0 001) and controls (26, 10‐39 pmoI/I,P<0 001). ACTH levels were also elevated in ectopic ACTH syndrome (0900 h median 34, 11‐152 pmol/l) compared to patients with Cushing's disease (0900 h median 8, 3‐19 pmol/l), but not to the same degree as ACTH precursors. In contrast with Cushing's disease, ACTH was secreted in a non‐pulsatile fashion. ACTH precursors but not ACTH itself correlated wtih plasma Cortisol in patients with ectopic ACTH syndrome (r= 0‐65,P<005). Chromatographic analysis of plasma from a patient with ectopic ACTH syndrome confirmed ACTH precursors and not ACTH to be the predominant circulating form. With the cross‐reactivity of proopiomelanocortin and pro‐ACTH in the ACTH IRMA of<1 and<10% respectively, ACTH precursors could represent all the ACTH immunoreactivity in patients with ectopic ACTH syndrome.CONCLUSIONSEctopic ‘ACTH’ is characterized by aberrant processing of proopiomelanocortin and should be more accurately referred

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02468.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEThe electron transfer system molecules, NADPH‐cytochrome P450 reductase (Red) and cytochrome b5 (bS) are known to increase the relative activity of 17,20‐lyase to 17α‐hydroxylasein vitro.Consistent with this hypothesis, we have reported recently that adrenocortical adenomas from patients with Cushing's syndrome that produced exceptionally high concentrations of androgens also contained more b5 mRNA as well as greater 17,20‐lyase activity than adenomas that produced low concentrations of androgens. This finding was suggestive but inconclusive in linking b5 functionally to this difference in adenoma 17,20‐lyase activity. In the present study, we have extended this finding by examining the effect of bS on microsomal 17,20‐lyase activity using an antibody against cytochrome b5.DESIGNBiochemical quantitation of the content of b5 and Red activity in the microsomal fraction of the tumours and determination of 17,20‐lyase activity In the microsomes in the presence or absence of an antibody against b5.PATIENTSSeven patients with a clinical diagnosis of Cushing's syndrome secondary to benign adrenocortical adenoma were studied.MEASUREMENTSThe microsomal activities of 17α‐hydroxylase, 17,20‐lyase and 3β‐hydroxysterold dehydrogenase were measured by in‐vitro enzyme assay with thin layer chromatography. Microsomal Red activity was assayed by measuring NADPH‐dependent cytochrome c reduction reaction. Cytochrome b5 concentration was determined by spectrophotometric analysis.RESULTSAn in‐vitro enzyme assay of microsomal fractions from the adenoma showed that the 17,20‐lyase activities of two adenomas that produced high concentrations of adrenal androgen were threefold greater than those of five other adenomas that produced low concentrations of androgens. Cytochrome b5 concentrations were greater in the two adenomas with high 17,20‐lyase activity than in the other adenomas, while no significant difference in Red activity was observed among all the adenomas. The increased 17,20‐lyase activity in the two adenomas was partially but significantly antagonized by an antibody against b5.CONCLUSIONSThese results suggest that differences in tissue b5 are functionally associated with differences in 17,20‐lyase activity in adrenocortical adenomas In Cushing's syndrome, resulting in a dissociated secretion of Cor

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02469.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVEA relationship between the serotoninergic and the opiatergic system in the pathogenesis of head pain is supported by several data. This study was carried out to investigate the neuroendocrine effects of sumatriptan, a specific serotonin agonist used in the treatment of migraine, on hypothalamic‐pituitary‐adrenal axis (PHA) hormones.DESIGNTwo consecutive studies were performed. In study A, eight subjects received a subcutaneous (s.c.) injection of sumatriptan (6 mg). In study B, a further six subjects were randomized to receive either sumatriptan or placebo.SUBJECTSHealthy volunteers recruited within the staff (eight males and six females) were studied.MEASUREMENTIn study A, plasma Cortisol and PRL were measured by direct RIA and β‐endorphin after extraction and chromatography. Samples were collected from 60 minutes before to 120 minutes after the administration of the drug, at 15‐minute intervals. According to the data of the first study, in study B, in addition to Cortisol and β‐endorphin, ACTH was also measured.RESULTSSignificant increases in the mean β‐endorphin and Cortisol concentrations were found in every subject receiving sumatriptan, while no significant changes were observed in prolactin plasma levels. Study B confirmed the activation of the pituitary‐adrenal axis, additionally demonstrating the release of ACTH, and indicated that placebo has no effects.CONCLUSIONAcute s.c. stimulation with sumatriptan activates the pituit

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02470.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SummaryOBJECTIVETSH‐binding inhibitory immunoglobulin (TBII) is undetectable in about 10% of untreated Graves' disease patients, but the clinical characteristics and immunological significance of this finding are unknown. In this study we evaluated the clinical characteristics of TBII negative Graves' disease.PATIENTSWe examined TBII in 1048 untreated patients at Kuma hospital from 1986 to 1990 and found 69 TBII undetectable patients (12 men and 57 women, mean age ± SEM 35 ± 2 years, group A).MEASUREMENTSWe compared the clinical characteristics and immunological findings of group A with 57 untreated TBII detectable Graves' patients who were selected randomly (11 men and 46 women, mean age ±SEM 40 ±2 years, group B). T4, TSH, FT4, FT3, 1231 thyroid uptake, TBII, thyroid stimulating antibodies (TSAb) and the volume of the thyroid using ultrasonography were measured at the first visit.RESULTSSerum T4, FT4 and FT3 levels in group A were significantly lower than those in group B (P<0 001). The values of TSAb in group A were significantly lower than those in group B (593±67 (mean±SE) vs 2143±280%, respectively,P<0001). The 1231 thyroid uptake in group A was significantly lower than that in group B (53 1 ±11 vs 61 ‐4±14%, respectively,P<0.01).The thyroid volume in group A was significantly smaller than that in group B (391 ±3 0 vs 51 3±3 3 ml, respectively,P<0 01). TSAb was undetectable in about 10% (6) of the TBII negative untreated Graves' patients at their first visit.CONCLUSIONIn the present study, untreated TBII negative patients with Graves' disease were characterized by mild elevation of thyroid hormones, mildly elevated123l uptake, weak TSAb activities and small goitres. The finding of both TBII and TSAb negative titres in untreated Graves' disease patients was

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1994.tb02471.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY