ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1560.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVES We wished to compare peak and incremental rise in plasma cortisol in response to insulin induced hypoglycaemia (IIH) stress test, i.m. glucagon stimulation test (IMGST) and short Synacthen test (SST) in patients with pituitary disease, using a modern radioimmunoassay for cortisol. We compared the three stimulants using receiver operator characteristic (ROC) plots, assuming a cortisol threshold of 500 nmol/l or 580 nmol/l for the IIH stress test which we used as the standard from which to evaluate the SST and the IMGST.PATIENTS AND DESIGN We prospectively studied 16 patients (8F, 8M mean age 43.69 ± 3.72 years) admitted to the investigation ward for IIH stress test and who were asked to undergo two additional tests (IMGST and SST) on consecutive days.MEASUREMENTS We measured serum cortisol at baseline, 30, 45, 60, 90 and 120 minutes during the IIH stress test; baseline, 150 and 180 minutes during GST, and baseline and 30 minutes during the SST.RESULTS There was a significant rise in cortisol from baseline in all tests (P < 0.001). There was no significant difference among the peak plasma cortisol responses or the incremental rises in plasma cortisol following IMGST, SST and IIH stress test (repeated measures ANOVAF = 0.704,P = 0.503;F = 0.238,P = 0.79). The ROC plots clearly showed that the SST has poor diagnostic utility at both IIH thresholds, compared with the IMGST.CONCLUSION The peaks and incremental rises in cortisol following all three tests are comparable. Using the insulin induced hypoglycaemia stress test as a reference and peak cortisol thresholds of 500 and 580 nmol/l as discriminating variables, the short Synacthen displayed poor diagnostic utility when compared to the i.m. glucagon stimulation test. The short Synacthen may be misleading if used as a screening

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1562.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVES Laparoscopic adrenalectomy offers the potential benefits of a smaller operation with more rapid hospital discharge, compared to open surgery. Only a few small series have been reported so far. We describe our preliminary experience of 14 adrenalectomies using this new technique.DESIGN Review of all adrenalectomies (with the pre‐operative intention of laparoscopic removal) performed in an endocrine unit whose surgeon already had abdominal laparoscopic experience, particularly with cholecystectomy.PATIENTS AND MEASUREMENTS Twelve patients (3 with Conn's syndrome, 3 Cushing's syndrome, 1 Cushing's disease, 2 phaeochromocytomas and 3 adrenal incidentalomas) were operated between September 1993 and February 1996. Operating times, operative technique, time from surgery to discharge, outcome and all complications were recorded prospectively. Comparative data were obtained from 14 consecutive open adrenalectomies performed by the same surgeon between February 1989 and February 1995.RESULTS Fourteen glands were removed, two with a cholecystectomy, in 12 operations. Operating time (mean (range) 120 (60–225) min) was reduced with experience. Positioning the patient in the right lateral position facilitated left adrenalectomy. Time to discharge (mean (range)) was 5.3 (1–12) days. There were relatively minor complications in three patients, including two with Cushing's syndrome: a hernia at a port site, intra‐peritoneal/wound haemorrhage and a pressure sore. Time to discharge for open adrenalectomy (mean (range)) was 6.5 (2–11) days and one case was complicated by wound infection.CONCLUSIONS Laparoscopic adrenalectomy is a practical technique for appropriately trained surgeons who regularly undertake adrenalectomy. The smaller incisions offer potential advantages, particularly for patients with poor tissue quality due to Cushing's syndrome, but tissue haemorrhage may still be a problem in these patients. Time to hospital discharge was similar to th

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1557.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE While inferior petrosal sinus (IPS) sampling correctly diagnoses pituitary‐dependent Cushing's syndrome if a significant ratio of plasma ACTH between the IPS and the peripheral blood is demonstrated, little has been said about the significance of a negative ratio in Cushing's disease (e.g. a false‐negative result). This study evaluates the results of IPS sampling in patients with Cushing's disease, and compares them with both imaging findings and transsphenoidal examination.DESIGN The results of IPS sampling were retrospectively compared with both imaging findings and transsphenoidal examination. IPS samples were obtained before and 2, 5 and 10 minutes after intravenous administration of 100 μg of CRH.PATIENTS Thirty‐two patients with Cushing's disease were evaluated. All subsequently underwent transsphenoidal examination of the pituitary gland.MEASUREMENTS The ratio of the ACTH concentrations at the IPS and in the peripheral blood (IPS : P ratio), and the ratio of the ACTH concentrations between the IPSs (interpetrosal ratio) were calculated. Radiographic evaluation of the pituitary gland was performed with magnetic resonance imaging (MRI, 29 cases) or computed tomography imaging (CT, 3 cases).RESULTS Transsphenoidal examination of the pituitary gland revealed a microadenoma in 27 cases. Radiological imaging showed a signal compatible with a microadenoma in 22 cases (68.8%), and correctly located the tumour at the side found at surgery in 14 of the 22 cases with positive transsphenoidal findings (MRI 13 cases, CT 1 case, overall 63.6%). Successful bilateral catheterization was accomplished in 30 patients (93.8%). Samples before and after CRH stimulation were drawn in 24 cases. No major complications were observed with the technique. IPS catheterization correctly predicted Cushing's disease (by means of a significant IPS : P ACTH ratio) in 27 of the 30 patients (90%) with basal sampling, and in 23 of the 24 cases with samples drawn before and after CRH administration (95.8%). Taking into account the 12 patients with a lateral microadenoma shown at transsphenoidal examination, IP sinus ACTH ratio was in agreement with the side recorded by the neurosurgeon in 8/12 cases (66.7%). MRi correctly located the tumour in 8/12 patients (66.7%). One patient showed no significant IPS : P ACTH ratio in any set of samples. His MRI showed no sign of a microadenoma. Two years later, another pituitary MRI evaluation showed a midline hypodense signal. The transsphenoidal examination revealed a microadenoma and the post‐operative plasma cortisol and urinary free cortisol fell to 293 nmol/l and 100 nmol/24 h, respectively.CONCLUSIONS Only when a significant IPS : P ACTH ratio is present can Cushing's disease be established by IPS sampling. The absence of a significant IPS : P ACTH ratio does not necessarily imply ectopic secretion of ACTH, nor does it exclude Cushing's disease. The results of lateralization by IPS sampling do not remove the need for a thorough transsphenoidal

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1550.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND Higher vasopressin (AVP) levels have been found in the inferior petrosal sinus ipsilateral to the ACTH‐secreting adenoma than in the contralateral one, suggesting a potential pathogenetic role of AVP in Cushing's disease.DESIGN In order to investigate AVP release, plasma ACTH and AVP concentrations were assayed in the inferior petrosal sinuses and in the peripheral blood before and after CRH stimulation.PATIENTS Twenty patients with Cushing's disease and 12 with other pituitary diseases were subjected to simultaneous and bilateral inferior petrosal sinus sampling for diagnostic purposes. Ten healthy sex and age‐matched subjects served as control for peripheral AVP values.MEASUREMENTS Plasma ACTH concentrations were measured by RIA using commercial kits. Plasma AVP concentrations were assayed by RIA in acetone extracts of 1–2 ml plasma.RESULTS Plasma AVP levels in the inferior petrosal sinuses were significantly higher in Cushing's disease than in patients with other pituitary diseases (P<0.05) and in both groups AVP levels were higher in the inferior petrosal sinuses than in the peripheral blood (P<0.01). In Cushing's disease, ACTH, but not AVP levels, were higher in the inferior petrosal sinus ipsilateral to the adenoma than in the contralateral one (P<0.01). Seven patients showed a significant ACTH and AVP increase (greater than 50% of baseline) after CRH stimulation in the inferior petrosal sinus ipsilateral to the adenoma. Conversely, no change was found in AVP levels in the remaining 13 patients. When AVP values were analysed in relation to surgical cure, higher inferior petrosal sinus levels (P<0.05) were found in 6 patients with poor outcome: 4 of these patients had significantly decreased plasma AVP concentrations (by 32–43% of baseline) after CRH bolus. Peripheral AVP levels were similar in healthy subjects and patients with Cushing's disease whereas they were significantly reduced in patients with other pituitary diseases (P<0.002).CONCLUSIONS The results of this study show that patients with Cushing's disease and poor surgical outcome had the highest AVP levels in our series. CRH administration caused different effects on AVP levels: it increased them in 35% of patients whereas there was no response in the remaining patients. On the basis of these findings, it is hypothesized that AVP might be involved in the persistence of ACTH hypersecretion in a subset of patients poorly

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1551.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Exophthalmos was noted in 4 of the 12 patients reported by Harvey Cushing in 1932. Although exophthalmos has often been included in clinical descriptions, no previous study has reported actual measurements in patients with active and treated Cushing's syndrome, and in control patients. The aim of this study was to obtain these measurements.PATIENTS Thirty‐one patients with active Cushing's syndrome (19 iatrogenic), 15 with treated Cushing's syndrome, 18 with Graves' ophthalmopathy, 59 control patients, and 3 patients with active Cushing's syndrome plus a family or personal history of thyroid disease.DESIGN AND MEASUREMENTS A consecutive series of patients with active and treated Cushing's syndrome were assessed. They were compared with patients with Graves' ophthalmopathy, and with control patients. Exophthalmos was assessed by the author using a Hertel meter. Urinary free cortisol was measured on patients with Cushing's syndrome, and serum thyroxine was estimated for them, and for the patients with Graves' ophthalmopathy.RESULTS Exophthalmos exceeding 16 mm (>2 SD above normal mean) was found in 45% of active Cushing's syndrome, 21% of iatrogenic Cushing's syndrome, 20% of treated Cushing's syndrome, 2% of normal controls, and 77% of patients with Graves' ophthalmopathy. No patient with Cushing's syndrome had significant symptoms due to exophthalmos.CONCLUSION Patients with active Cushing's syndrome have statistically significant exophthalmos. This rarely causes symptoms, and diminishes when cortisol concentrations become normal. Cushing's syndrome and autoimmune thyroid disease may coexist in patients wi

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1559.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND Hormone replacement in hypopituitary adults attempts to reproduce normal physiology. Conventional regimens fail to mimic normal hormone profiles over 24 hours.OBJECTIVE To investigate the metabolic consequences of conventional hormone replacement in hypopituitary adults by measuring circulating levels of the major fuels, glucose, non‐esterified fatty acids (NEFA), glycerol and 3‐hydroxybutyrate (3‐OHB) over 24 hours in hypopituitary subjects and controls.SUBJECTS Ten GH and adrenocorticotrophin deficient hypopituitary adults on conventional replacement and 13 controls matched for age, sex and body mass index were studied. The patients received replacement with hydrocortisone twice daily (at 0730 and 1730 h; mean (range) daily dose 22 (10–30) mg/24 h) but not with GH. Other hormones were replaced as clinically necessary.MEASUREMENTS Circulating glucose, NEFA, glycerol and 3‐OHB levels were measured over 24 hours together with concentrations of cortisol (total and free), GH and insulin, and urinary free cortisol.RESULTS Levels of glucose, NEFA and 3‐OHB were lower in patients than controls (mean ± SEM) (4.3 ± 0.1vs5.3 ± 0.1 mmol/l,P = 0.0001; 291 ± 46vs448 ± 48 μmol/l,P = 0.015; 78 ± 8vs136 ± 24 μmol/l,P = 0.035, respectively) before breakfast. This decrease in glucose, NEFA and 3‐OHB was observed in the patient group throughout the night, from midnight to breakfast. For NEFA, the decrease persisted throughout the 24 hours. Glycerol did not differ significantly in patients and controls. Integrated levels of total and free plasma cortisol, and 24‐hour urine cortisol excretion, were normal in patients but total and free plasma cortisol concentrations overnight were markedly decreased (overnight area under the curve (AUC) of total cortisol: 440 ± 154vs1593 ± 267 nmol/l h,P = 0.0024; overnight AUC of free cortisol: 24 ± 8vs161 ± 26 nmol/l h,P = 0.0001). GH levels were low throughout the whole 24 hours in the patient group (24‐hour AUC: 10.6 ± 5.1vs74.6 ± 19.6 mU/l h,P = 0.008).CONCLUSIONS Hypopituitary adults on conventional hormone replacement regimens have low concentrations of metabolic fuels, glucose, non‐esterified fatty acids and 3‐hydroxybutyrate throughout the night, possibly related to GH deficiency or to decreased overnight circulating cortisol levels. This overnight fuel deficiency may und

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1552.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE There is increasing evidence for the role of cytokines in pituitary differentiated function and tumorigenesis, but the spectrum of cytokines found in the pituitary is unknown. Therefore profiles of cytokine expression were determined in different human anterior pituitary adenoma sub‐types.DESIGN The reverse transcriptase‐linked polymerase chain reaction (PCR) was used to identify the presence of cytokine mRNA within human pituitary adenomas.PATIENTS Seventeen pituitary adenoma biopsies removed at transsphenoidal surgery were examined: 4 somatotrophinomas, 7 non‐functional adenomas, 4 prolactinomas, one case of Cushing’s disease and one case of Nelson's syndrome.MEASUREMENTS RNA was extracted from each adenoma biopsy and reverse transcribed into cDNA. This was specifically amplified in a PCR using oligonucleotide primers complementary to each cytokine. The cytokines investigated were interleukin (IL) ‐lα, IL‐lβ, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, tumour necrosis factor (TNF)‐α, TNF‐β and transforming growth factor (TGF)‐β1, β2and β3. The products of each PCR were visualized using agarose gel electrophoresis.RESULTS All 17 adenomas expressed IL‐8 transcripts, but no expression of IL‐2, IL‐5 or IL‐7 was found. IL‐6 was expressed in all 4 somatotrophinomas, 3 of 7 non‐functional tumours, 2 of 4 prolactinomas and in the single case of Nelson's syndrome. At least one of the 3 isoforms of TGF‐β was found in all but 2 tumours; one prolactinoma and one non‐functional adenoma. IL‐1α, IL‐β, IL‐4, TNF‐α and TNF‐β were expressed sporadically by individual adenomas.CONCLUSION These data suggest that whilst IL‐8 may be important, the local expression of the cytokin

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1554.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVES A transcription factor Ad4BP/SF‐1 is implicated in the differentiation of gonadotrophs in the pituitary gland, but it is not known whether human pituitary cells express this factor. The present study aimed to disclose (1) whether human pituitary adenomas express Ad4BP/SF‐1, and (2) if this is the case, what kinds of adenoma express the factor.MATERIAL Total RNA was extracted from 23 pituitary adenomas obtained by transsphenoidal surgery, and subjected to Northern blot analyses using cDNAs of bovine Ad4BP/SF‐1, porcine FSH‐β, LH‐β and glycoprotein hormone‐β (GPH‐α) subunits as radiolabelled probes. These adenomas included 13 clinically non‐functioning adenomas, 1 GH/PRL‐producing adenoma, 6 GH‐producing adenomas, 2 PRL‐producing adenomas and 1 ACTH‐producing adenoma.RESULTS The expression of Ad4BP/SF‐1 exactly coincided with the expression of FSH‐β. Thus 5 out of 13 clinically non‐functioning adenomas expressed Ad4BP/SF‐1 and only these 5 adenomas expressed FSH‐β. Interestingly, only one of the GH‐producing adenomas also expressed Ad4BP/SF‐1 as well as FSH‐β. GPH‐α was expressed in 4 non‐functioning adenomas and 2 hormonally functioning adenomas, but did not necessarily coincide with Ad4BP/SF‐1 expression. None of the 23 adenomas we tested expressed LH‐β, probably because LH‐β‐producing adenomas are rather rare.CONCLUSIONS The expression of FSH‐β was parallel with Ad4BP/SF‐1 expression, indicating that the expression of Ad4BP/SF‐1 is restr

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1555.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Allelic deletion of the retinoblastoma (Rb) gene on chromosome 13 has been reported in both pituitary and parathyroid tumours. We have investigated the roles of the Rb and the hereditary breast cancer susceptibility gene (BRCA2), which lie within 25 cM of each other on chromosome 13q12–14, in the multi‐step aetiology of endocrine tumours.PATIENTS AND MEASUREMENTS Seventy‐seven endocrine tumours (43 anterior pituitary, 22 parathyroid, 7 carcinoid, and 5 pancreatic islet cell tumours) with paired leucocytes have been examined for loss of heterozygosity (LOH) at the Rb and BRCA2 loci by using specific oligonucleotide primers for the PCR amplification of microsatellite polymorphisms at three intragenic Rb markers, Rb1.20, Rbi4 and D13S153, and D13S260 which is linked to the BRCA2 locus.RESULTS Seventy‐five of the 77 tumour–leucocyte pairs were informative and LOH was detected in 1 of 16 non‐functioning pituitary tumours, 1 of 8 prolactinomas, 3 of 19 parathyroid adenomas and 1 of 1 parathyroid carcinoma. All the 3 parathyroid adenomas with LOH were associated with aggressive clinical and histopathological features. Allele loss was not detected in any of the 16 somatotrophinomas, 2 corticotrophinomas, 1 gonadotrophinoma, 7 carcinoid tumours (6 bronchial, 1 metastatic intestinal) or 5 pancreatic islet cell tumours that were informative.CONCLUSIONS These results demonstrate that allelic deletions of the 13q12‐14 region occur in some pituitary adenomas and 16% of parathyroid adenomas. The extensive loss, which involves both the Rb gene and the BRCA2 locus, suggests that tumour suppressor genes in this region other than Rb or BRCA2 may be involved in the development and progression of

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.d01-1561.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY