Assessment of normal perisellar anatomy in 1.5 T T2-weighted MRI and comparison with the anatomic criteria defining cavernous sinus invasion of pituitary adenomas.

OBJECTIVE: The study aimed to evaluate the anatomical relations of sellar and perisellar structures with T2-weighted MRI and to apply criteria for cavernous sinus (CS) invasion by pituitary adenomas to normal sellar anatomy. METHODS: Thin slice (3 mm) coronal T2-weighted MR-images (1.5 Tesla) were obtained in 117 individuals (234 CS) without pituitary disorders (58 females, 59 males; age 17 months to 87 years). In 99 cases data indicating the presence of arterial hypertension (AH) were available, 25 with AH, 74 without AH. RESULTS: The medial wall of the cavernous sinus was detectable in 33% of cases. The inferior rim of the horizontal part of the ICA was located at the level of the sellar floor in 33%, below in 47%, and above in 20%. The mean distance between the both ICAs was 17.8 mm (range, 7-38 mm). The mean distance between the pituitary and the ICA in AH was significantly shorter than in patients without AH (Chi-square, p=0.01). There was contact between the gland and the ICA in 41.5% of the cases. In 16.7% (39 sides) of all 234 SCs investigated, the area of contact between the ICA and the gland was at least 25% of the vessel's circumference. The medial intercarotid line (ICL) was crossed by the pituitary gland in 9% (21 of 234 CS), the central ICL was touched in another 5% (11 of 234 CS), lateral ICL was never reached. There was a weak correlation with age: a more extensive lateral extension of the gland was seen in individuals older than 40 years compared to younger individuals (Chi-square, p=0.03). There was a marked difference in the anatomical findings between both sides in 41.9% of cases. CONCLUSION: Inter- and intra-individual variations of the perisellar anatomy and its relation to the pituitary gland exist, which are partly related to age and AH. This must be remembered when the invasiveness of pituitary adenomas is assessed in MRI.

[Investigation of diabetic men with erectile dysfunction to determine coronary flow reserve (CFR) and cardiac risk under medication with sildenafil (Viagra)]. / Untersuchung von Diabetikern mit erektiler Dysfunktion (ED) zur Bestimmung der CFR (koronare Flussreserve) und des kardialen Risikos unter Medikation mit Sildenafil (Viagra).

PURPOSE: Since Sildenafil (Viagra) has become available, there have been reports of death and cardiac risks associated with its use. As large doses of Sildenafil medication is often prescribed particularly in diabetic patients with erectile dysfunction (ED), our study was designed to evaluate the coronary flow reserve (CFR) and possible resulting cardiac risk specifically in diabetic men. MATERIALS AND METHODS: Because these men often suffer from clinically significant ischaemic heart problems without their knowledge and without symptoms, all of our patients were examined by treadmill ECG and CFR. RESULTS: In 44 men (35 - 74 years) with type I and II diabetes also suffering from ED objectified by FCDS measurement of the penile vessels, a surprisingly high rate of objective cardiac problems were found, which were then verified by coronary angiography. These patients are at risk for ischaemic problems during Sildenafil-assisted intercourse and were excluded from further study. Interestingly, only 3 of theses 11 men would have been detected by conventional examinations. Patients free of coronary stenosis who received 50 mg Sildenafil (20 patients) showed no cardiac problems during treadmill exercise and CFR measurement. CONCLUSIONS: Coronary flow reserve in diabetic men lies at the lower end of the normal range, but is not further decreased by Sildenafil. However, diabetics with ED frequently showed coronary artery stenosis that was not clinically symptomatic. Furthermore, conventional cardiological examinations often fail to detect these patients, although they are at ischaemic risk during medically assisted intercourse. Furthermore, although 5 of 20 men who received Sildenafil had an increase in penile blood flow without sexual stimulation, only 7 of 20 were responders to Sildenafil after take home medication. Thus, Sildenafil medication is not a suitable test medication for organic erectile dysfunction.

[The choice between transperitoneal and retroperitoneal adrenalectomy. A prospective study]. / Transperitoneale oder retroperitoneale Adrenalektomie. Ergebnisse einer prospektiven Verlaufsbeobachtung.

INTRODUCTION: The aim of this prospective study was to evaluate the optimal surgical approach to endoscopic adrenalectomy. PATIENTS AND METHODS: Between March 1997 and February 2003, we performed 221 endoscopic adrenalectomies in 202 patients (right side 83, left side 100, bilateral 19), with an conversion rate of 2,5%. In 197 patients endoscopic adrenalectomy was carried out via retropertioneal approach 128 times and via transperitoneal approach 88 times. RESULTS: Endoscopic adrenalectomy was performed in 98% of the total number patients. No statistically significant influence ( P=0.05) was found for the parameters intraoperative blood loss, rate of postoperative complications, or duration of hospitalization in regard to the procedure. The operative time and learning curve were significantly longer with the retroperitoneal approach. Multivariate analysis identified surgical approach, tumor size (5 cm), and body mass index (25) as independent factors for operative time. CONCLUSION: The lateral transperitoneal approach is the optimal procedure for endoscopic adrenalectomy.

[Sildenafil does not change coronary flow reserve in diabetics with erectile dysfunction]. / Sildenafil verändert nicht die koronare Flussreserve bei Diabetikern mit erektiler Dysfunktion.

BACKGROUND AND AIM OF STUDY: Disturbance of the microvascular coronary circuit is common in diabetics with erectile dysfunction. We investigated effects of sildenafil on coronary flow reserve (CFR) of the left anterior descending branch. PATIENTS AND METHODS: 43 diabetics (aged 59 +/- 7 years) with erectile dysfunction and without symptoms of coronary artery disease were selected. Cardiac diagnosis, including stress ECG and echocardiography was performed in all. Because of the clinical suspicion of coronary artery disease coronary angiography was performed in 16 of them. Severe coronary artery disease was confirmed in 12 patients who were excluded from further analyses as well as 10 diabetics in whom coronary flow measurements were not possible. In the other 21 diabetics, adenosine-mediated CFR was calculated at baseline and 1 hour after ingestion of 50 mg sildenafil by transthoracic Doppler echocardiography. RESULTS: CFR at baseline was at the lower level of the normal range in 17/21 diabetics (median 245 %, range 210 - 490 %). CFR decreased insignificantly in 12/21 patients after sildenafil administration (Delta CFR -10 %, p = 0.3). Patients with a body mass index > 25 kg/m(2), and left ventricular hypertrophy had the highest reduction of CFR after sildenafil, but a drop of the CFR below 200 % was not observed in any patient. Systemic blood pressure dropped significantly from 130/80 mmHg to 120/72 mmHg (p < 0.002). CONCLUSION: Diabetics with erectile dysfunction often have a CFR in the lower range of normal. Sildenafil did not further reduce CFR. Asymptomatic, severe coronary artery disease often can be found in diabetics with erectile dysfunction. Cardiological screening for contraindications for sildenafil seems mandatory in diabetics with a high cardiovascular risk profile.

p53 mutations in adrenal tumors: Caucasian patients do not show the exon 4 "hot spot" found in Taiwan.

Mutations in the p53 tumor suppressor gene are frequently present in human cancers but have rarely been described in benign tumors. We previously reported mutations in the "hot spots" between exons 5-8 of the p53 gene in adrenocortical carcinomas but not in adenomas. Recently, a previously unknown hot spot in exon 4 of the p53 gene was described in adrenal adenomas and pheochromocytomas of Taiwanese patients. We, therefore, investigated whether these mutations are also present in Caucasian patients from the U.S. and Europe. We analyzed tumor tissue of 12 aldosterone-producing adenomas, 7 cortisol-producing adenomas, and 6 pheochromocytomas. Overexpression of the p53 protein was investigated by immunohistochemistry. Point mutations within exon 4 were identified by polymerase chain reaction (PCR) amplification and direct sequencing of the PCR product. The pYNZ22 microsatellite located on chromosome 17p, close to the p53 gene, was used to screen for allelic loss (LOH) of the p53 gene. Overexpression of p53 was not identified in any of the adenomas and pheochromocytomas. Point mutations within exon 4 were found in 0/25 tumors. LOH was present in 1/13 informative adenomas and 0/2 informative pheochromocytomas. We conclude that p53 mutations do not play a major role in the tumorigenesis of adrenal adenomas and pheochromocytomas of Caucasian patients. Thus, ethnic and environmental factors may be responsible for the mutational spectrum found in Taiwanese patients.

Clonal composition of human adrenocortical neoplasms.

The mechanisms of tumorigenesis of adrenocortical neoplasms are still not understood. Tumor formation may be the result of spontaneous transformation of adrenocortical cells by somatic mutations. Another factor stimulating adrenocortical cell growth and potentially associated with formation of adrenal adenomas and, less frequently, carcinomas is the chronic elevation of proopiomelanocortin-derived peptides in diseases like ACTH-dependent Cushing's syndrome and congenital adrenal hyperplasia. To further investigate the pathogenesis of adrenocortical neoplasms, we studied the clonal composition of such tumors using X-chromosome inactivation analysis of the highly polymorphic region Xcen-Xp11.4 with the hybridization probe M27 beta, which maps to a variable number of tandem repeats on the X-chromosome. In addition, polymerase chain reaction amplification of a phosphoglycerokinase gene polymorphism was performed. After DNA extraction from tumorous adrenal tissue and normal leukocytes in parallel, the active X-chromosome of each sample was digested with the methylation-sensitive restriction enzyme HpaII. A second digestion with an appropriate restriction enzyme revealed the polymorphism of the region Xcen-Xp11.4 and the phosphoglycerokinase locus. Whereas in normal polyclonal tissue both the paternal and maternal alleles are detected, a monoclonal tumor shows only one of the parental alleles. A total of 21 female patients with adrenal lesions were analyzed; 17 turned out to be heterozygous for at least one of the loci. Our results were as follows: diffuse (n = 4) and nodular (n = 1) adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome, polyclonal pattern; adrenocortical adenomas (n = 8), monoclonal (n = 7), as well as polyclonal (n = 1); adrenal carcinomas (n = 3), monoclonal pattern. One metastasis of an adrenocortical carcinoma showed a pattern most likely due to tumor-associated loss of methylation. In the special case of a patient with bilateral ACTH-independent macronodular hyperplasia, diffuse hyperplastic areas and a small nodule showed a polyclonal pattern, whereas a large nodule was monoclonal. We conclude that most adrenal adenomas and carcinomas are monoclonal, whereas diffuse and nodular adrenal hyperplasias are polyclonal. The clonal composition of ACTH-independent massive macronodular hyperplasia seems to be heterogeneous, consisting of polyclonal and monoclonal areas.

[Diagnosis and therapy of malignant peritoneal mesothelioma]. / Diagnostik und Therapie des malignen peritonealen Mesothelioms.

Malignant peritoneal mesothelioma is an uncommon tumor with great diagnostic and therapeutic problems. Symptoms, clinical features and course of the disease are described in three patients which were seen at our hospital within the last years. At the beginning there are often severe weight loss, malaise and sometimes fever of unknown origin. Abdominal pain, increased abdominal girth or nausea indicate advanced tumor stages in most cases. Ultrasonography and computed tomography of the abdomen can give important information during the diagnostic approach. Nevertheless, the definite diagnosis can only be established by laparoscopy or open surgery with biopsy for a histological examination. Despite intern and extern radiotherapy as well as systemic and/or local chemotherapy the prognosis of malignant peritoneal mesothelioma remains unfavourable. Mean survival time ranges from six to 18 months.

[Diagnosis and therapy of asymptomatic adrenal tumors]. / Diagnostik und Therapie asymptomatischer Nebennierentumoren.

Adrenal tumours had been discovered incidentally (since 1981) in 32 patients (23 females and nine males; mean age 54 [25-73] years) who had had computed tomography (CT) or ultrasonography for other reasons: none had a history or symptoms of such tumour. Tumours were bilateral in eight, right or left-sided in 12 each: all had been confirmed by CT. Average tumour size was 3 cm (1-9 cm). Three patients had cortisol-producing adrenal tumours, and there was one benign phaeochromocytoma (abnormally high adrenaline and noradrenaline excretion). Fine-needle biopsies in two patients revealed a benign histology. An adrenalectomy was performed in eight patients (the one phaeochromocytoma, six adenomas and one ganglioneuroma). Follow-up CT in 11 of the non-operated patients 6-48 months later (mean of 14 months) did not demonstrate any increase in tumour size so that a waiting attitude seems justified: benign tumours are clearly much more frequent than malignant ones. However, if the tumour diameter is greater than 6 cm, an adrenalectomy is indicated because of the danger of malignancy.

[Treatment of metastatic adrenal carcinoma with suramin]. / Behandlung des metastasierten Nebennierenkarzinoms mit Suramin.

A right adrenocortical carcinoma (weighing 978 g) was removed from a 45-year-old man in April 1986, the tumour bed then being irradiated with 40 Gy. Subsequently discovered multiple lung metastases were treated with cisplatin, etoposide and bleomycin, without improvement. Treatment with mitotane (Lysodren) was also without effect and had to be discontinued because of severe side effects. Treatment with suramin (Germanin) was begun in August 1987. After a loading dose of 10.7 g for six weeks the lung metastases regressed almost completely. But lung metastases were again demonstrated in January 1988 during a low-dose maintenance regimen of suramin. Increased dosage arrested further growth, but achieved no regression of the metastases. The patient died unexpectedly in April 1988 of acute circulatory failure. Suramin administration had been discontinued six weeks earlier because of bronchopneumonia and general deterioration. Thrombocytopenia, coagulation disorders and moderate proteinuria were the side effects of suramin treatment.

The effect of sodium valproate in Cushing's disease, Nelson's syndrome and Addison's disease.

UNLABELLED: We investigated the effect of sodium valproate on plasma ACTH and serum cortisol concentrations in different pathological states of ACTH hypersecretion. Five patients with pituitary dependent Cushing's syndrome, two patients with Nelson's syndrome and five patients with Addison's disease were studied. Neither a single dose nor long term administration of sodium valproate resulted in a significant decrease of plasma ACTH levels in patients with Cushing's disease and Nelson's syndrome. Furthermore, the response of ACTH and cortisol to stimulation with lysine-vasopressin was unaffected during acute and chronic treatment. Patients with Addison's disease showed a slight attenuation of the ACTH response to lysine-vasopressin as compared to placebo but the difference was not statistically significant. IN CONCLUSION: sodium valproate does not appear to be effective in controlling ACTH hypersecretion in pituitary dependent Cushing's syndrome.

Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in Cushing's syndrome.

We determined the adrenostatic potential of low-dose nonhypnotic etomidate in six patients with Cushing's syndrome (ectopic Cushing's syndrome, n = 2; Cushing's disease, n = 3; bilateral adrenal adenoma, n = 1). Etomidate was given as a continuous infusion for 32 h in a dose of 2.5 mg/h (n = 5) or 0.3 mg/kg/h (n = 3), respectively. Saline was given during a control period. The responsiveness to exogenous ACTH was studied during placebo and 7 and 31 h after commencing etomidate by administration of 250 micrograms 1-24 ACTH i.v. Etomidate (2.5 mg/h) led to a consistent decrease in serum cortisol in all patients from a mean of 39.4 +/- 13.3 to 21.1 +/- 5.7 micrograms/dl after 7 h (P less than 0.05 compared with placebo). After 24 h cortisol was reduced further to a mean steady state concentration of 12.3 +/- 5.7 micrograms/dl (P less than 0.05). At the end of the infusion period the cortisol increase in response to ACTH was reduced but not abolished. In contrast, a dose of 0.3 mg/kg/h etomidate induced unresponsiveness of serum cortisol to exogenous ACTH within 7 h. However, sedation was observed in two out of three patients at this dose, while during etomidate in a dose of 2.5 mg/h no side effects were seen. We conclude that low-dose nonhypnotic etomidate reduces serum cortisol to within the normal range in patients with Cushing's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

[Adrenostatic treatment of ACTH-dependent Cushing syndrome using metyrapone and aminoglutethimide]. / Adrenostatische Therapie mit Metyrapon und Aminoglutethimid beim ACTH-abhängigen Cushing-Syndrom.

The adrenostatic effect of metyrapone (Metopiron) and aminoglutethimide (Orimeten) was assessed retrospectively in ten patients with ACTH-dependent Cushing's syndrome, four of them with the ectopic form. Five patients received metyrapone only, the other five both metyrapone and aminoglutethimide. Persistent lowering of the serum cortisol level was achieved in all, after an observation period of two weeks to four years. The intended therapeutic level of below 16 micrograms/100 ml was achieved in seven patients. In the course of treatment there was a rise in mean plasma ACTH concentration, but without an "escape" phenomenon. The adrenostatic treatment had to be limited, if at all, only because of side effects, which in two patients required that the drug administration be terminated. It is concluded that adrenostatic treatment with metyrapone and aminoglutethimide is effective and practical. It is suitable not only in the management of florid Cushing's syndrome, but also for long-term treatment when complete cure is not possible.