Incidence and clinical relevance of RET proto-oncogene germline mutations in pheochromocytoma patients.

BACKGROUND: Autosomal dominant cancer syndrome--multiple endocrine neoplasia type 2 (MEN 2), may exist more often than expected in patients with pheochromocytoma. Germline mutations identified recently in MEN 2 can be revealed by genetic screening. OBJECTIVE: To evaluate the frequency of RET (rearranged during transfection) mutations in patients with pheochromocytoma. DESIGN AND METHODS: We genetically screened germline mutations in the RET proto-oncogene and clinically re-evaluated patients with pheochromocytoma. A pentagastrin test and other biochemical studies were performed in all patients. SETTING: Department of Internal Medicine and Hypertension, The Medical University of Warsaw, Warsaw, Poland and the Department of Nephrology and Hypertension, Albert Ludwigs University, Freiburg, Germany. PARTICIPANTS: Seventy seven unselected patients with pheochromocytoma (19 men, 58 women, mean age: 51.55 +/- 1.5 years; pheochromocytoma confirmed histopathologically) out of 162 diagnosed and treated in the years 1957-1998 in the Department of Internal Medicine and Hypertension in Warsaw, Poland. The other 85 patients did not respond to the written invitation. MAIN OUTCOME MEASURES: The finding of RET mutations and diagnosis of MEN 2 in patients with pheochromocytoma. RESULTS: Genetic testing revealed germline mutations in the RET proto-oncogene in six patients (7.8%). All carriers had mutation of exon 11, codon 634: TGC to CGC. In four patients with this mutation, medullary thyroid carcinoma (MIC) was diagnosed and in three cases, surgically treated. Biochemical parameters: parathormone 31.88 +/- 2.87 pg/ml, calcitonin: 0 min 0.23 +/- 0.14 ng/ml; 2 min 0.49 +/- 0.21 ng/ml; 5 min 0.48 +/- 0.21 ng/ml, metoxycatecholamines: 601.62 +/- 42.71 microg/24h, epinephrine: 1.94 +/- 0.17 microg/24h, norepinephrine 13.96 +/- 1.3 microg/24h, carcinoembryonic antigen (CEA) 9.94 +/- 4.3 ng/ml. Ambulatory blood pressure monitoring (ABPM): systolic blood pressure (SBP): 116 +/- 1.9 mmHg, diastolic blood pressure (DBP): 73.7 +/- 0.9 mmHg. Clinical, biochemical and imaging procedures did not reveal any recurrence of pheochromocytoma in the 77 patients studied. CONCLUSIONS: Patients with pheochromocytoma should be genetically screened for mutations of the RET proto-oncogene. These patients should undergo clinical screening for MEN 2. In addition, genetic studies can be useful for the screening of the families of the carriers.

Endothelin-1 and neuropeptide Y plasma concentrations in renal venous blood of hypertensive patients with unilateral renal artery stenosis.

The aim of the study was to investigate endothelin-1 (ET-1) and neuropeptide Y (NPY) plasma concentrations in renal venous blood of hypertensive patients with unilateral renal artery stenosis (URAS). The study was performed in 22 patients with URAS and 18 patients diagnosed as essentially hypertensive. In each subject renal arteriography and renal vein catheterisation was performed. Blood samples for ET-1, NPY and plasma renin activity (PRA) were withdrawn from renal veins and vena cava inferior, and for ET-1 and NPY from the aorta. Patients with URAS were divided in two subgroups according to the renal vein renin ratio. Both in nine patients with URAS and ratio > 1.5 and in 13 patients with URAS and ratio < 1.5, ET-1 and NPY plasma concentrations evaluated in renal venous blood of the ischaemic kidney were not different from those assessed in the contralateral side, in vena cava inferior and in the aorta. In essential hypertension, the mean ET-1 and NPY plasma concentrations of both renal veins were not different from the ET-1 and NPY plasma values assessed in renal vein of stenosed and contralateral side, vena cava and aorta of patients with URAS with and without activation of the renin system. Our study indicates that chronic ischaemia does not affect ET-1 and NPY plasma concentrations in renal venous blood of hypertensive URAS patients both with and without activation of the renin system.

[Efficacy of spiral computed tomography in evaluation of renal arteries in patients with renovascular hypertension]. / Skutecznosc spiralnej tomografii komputerowej w ocenie tetnic nerkowych u pacjentów z podejrzeniem nadcisnienia naczyniowo-nerkowego.

UNLABELLED: The aim of this study is an estimation of efficacy of spiral computed tomography (SCT) in evaluation renal arteries in patients with renovascular hypertension. SCT was performed in 54 patients (32 females and 22 males) by means of Picker PQ 2000. The thickness 4 mm, index 4 mm, pitch 1.0. Contrast agents-Uropolinum 75% or Ultravist 350 were applied automatically 3-4 mm/sec. with delay 20-22 sec. Secondary reconstruction with 2 mm leyers was performed by Maximum Intensity Projection (MIP). In all patients the abdominal arteriography was performed as a reference method. The coincidence of both methods in evaluation of renal arteries occlusion or stenosis was estimated by Cohen kappa coefficient. In addition, sensitivity and specificity of SCT were estimated. RESULTS: Consistence of SCT and arteriography for right, left and additional renal artery were as follows: 0.914, 0.92, 0.85. Sensitivity and specificity SCT for rigt, left and additional renal artery were as follows: 95.5% and 95.8%, 96.5% and 95.8%, 50% and 100%. The highest efficacy of SCT was noted in ostium, the most difficult place in evaluation of renal artery during arteriography examination.

[Morphologic and functional assessment of renal artery stenosis: use of combined MR angiography and MR renography--preliminary report]. / Morfologiczna i czynnosciowa ocena zwezenia tetnicy nerkowej: zastosowanie polaczonej angiografii i renografii MR--doniesienie wstepne.

PURPOSE: To assess the possibility of use of multiphase magnetic resonance angiography for simultaneous acquiring of angiographic images and curves of contrast enhancement of renal cortex, medulla and pyelocalyceal system and evaluation of quality of obtained images. MATERIAL AND METHODS: Twenty-four patients suspected of having renal artery stenosis underwent power-injection of 30 ml of Gd-DTPA (3 ml/sec). From 10 to 360 seconds after the beginning of the injection, 3D MRA sequence was performed multiple times. Acquisition time of single phase of MR examination was 7.5-8 sec (TR = 5 ms, TE = 1:6 ms, single 7 cm thick slab with 35 partitions, 164 x 512 matrix). First three phases were used to obtain angiographic images. All phases were used to obtain curves of renal cortical, medullary and pyelocaliceal enhancement. Two readers evaluated quality of MRA images, as well as, quality of enhancement curves. RESULTS: 21 of 24 MRA examinations were of good, 2 of fair and none of poor quality. Quality of enhancement curves was good in 22 cases. It was suboptimal in 2 cases because of irregular breath-holding. Maximum number of acquisitions per minute was 4-5. Eight accessory, 2 obstructed and 9 stenosed renal arteries were visualized. Renographic curves were abnormal in 8 patients. CONCLUSIONS: MRA sequence with short acquisition time enables simultaneous acquisition of angiographic images and renographic curves of good quality. With further reduction in acquisition time it may be possible to obtain more points on MR renographic curves.

[Pheochromocytoma in a 81 year old woman treated with surgery--case report]. / Guz chromochlonny u 81. letniej chorej leczony operacyjnie--opis przypadku.

A case of pheochromocytoma in 81 year old woman hospitalized due to choledocholithiasis is reported. During premedication pronounced blood pressure elevation was observed. Operation was discontinued and diagnostic of pheochromocytoma was carried out. USG and CT scanning revealed right sided adrenal tumor. Elevated urine catecholamines and methoxycatecholamines were found. The patient underwent adrenalectomy and cholecystectomy. Histological examination confirmed diagnosis of pheochromocytoma. The patients done uneventful recovery.

Elevated endothelin-1 plasma concentration in patients with essential hypertension.

BACKGROUND: Endothelin-1 (ET-1) may play an important role in the development and maintenance of hypertensive states. In patients with essential hypertension, ET-1 plasma concentration increases or remains unchanged. The aim of the present study was to investigate ET-1 plasma concentration in patients with mild-to-moderate essential hypertension and its interrelationship with catecholamines, neuropeptide Y and atrial natriuretic peptide (ANP). METHODS: The study included 37 patients (mean age 38.2 +/- 1.6 years) with mild-to-moderate essential hypertension. The control group consisted of 21 healthy volunteers (mean age 35.6 +/- 1.4 years). ET-1, neuropeptide Y and ANP were determined by radioimmunoassay methods and catecholamine plasma concentration was determined radioenzymatically. RESULTS: Our study shows that plasma ET-1 and neuropeptide Y levels are elevated in patients with essential hypertension compared with a control group. No correlation was found in either of the groups between plasma ET-1 level and plasma neuropeptide Y, catecholamine or ANP concentrations. CONCLUSION: Our results suggest that ET-1 is relevant in the development and maintenance of elevated blood pressure.

Plasma fibrinogen as a risk factor for restenosis after percutaneous transluminal renal angioplasty in patients with atherosclerotic renal artery stenosis.

BACKGROUND: In contrast to those for coronary restenosis, the data regarding the risk factors for renal restenosis are limited. OBJECTIVE: To evaluate potential humoral risk factors for restenosis after percutaneous transluminal renal angioplasty (PTRA). METHODS: We studied 27 patients aged 54+/-10 years with atherosclerotic renal artery stenosis in a 1-year prospective follow-up. Restenosis (confirmed by angiography) occurred in eight patients 1-6 months after PTRA. We detected no Doppler ultrasound evidence of restenosis in 19 patients throughout 1 year. Blood studies were done before PTRA for all patients, at the time of diagnosis of restenosis and, for those without restenosis, after 1 year. including determinations of fibrinogen, lipids, platelets and leukocytes. RESULTS: The mean level of fibrinogen in patients who experienced restenosis was higher than that in those who did not (450+/-150 mg% versus 337+/-57 mg%, P < 0.01) and remained unchanged for both groups during follow-up. The other parameters did not differ between the groups before PTRA and did not change over time, with the exception of platelet count in patients who did not experience restenosis, which had decreased from 253+/-93G/l to 200+/-63G/l (P < 0.01) 1 year after PTRA. The logistic multiple regression analysis disclosed that an increment of fibrinogen level by 100 mg% was linked with an odds ratio for restenosis of 3.2 (95% confidence interval 1.1-9.8). CONCLUSIONS: Restenosis was associated with higher than normal levels of fibrinogen before PTRA. A high plasma fibrinogen level might play a role in the development of restenosis after PTRA.

Effects of the correction of renal artery stenosis on blood pressure, renal function and left ventricular morphology.

The aim of this study was to evaluate the effect of renal artery stenosis (RAS) correction in hypertensive patients on 24 h SBP, 24 h DBP, creatinine clearance (GFR), urinary albumin excretion (UAE) and LV morphology and mass (LVMI). A total of 61 hypertensive patients with RAS undergoing PTRA and/or surgical treatment entered the prospective study. The final analysis was done in 44 patients (age range 45.8 +/- 16.2 years) with RAS (atherosclerosis (ASC) 31 patients, fibromuscular dysplasia (FMD) 12 patients, arteritis 1 patient) who underwent PTRA (34 patients) or surgical treatment (10 patients) and presented no Doppler signs of restenosis (or a new stenosis) during 1-year observation. The pre-interventional assessment repeated after 6 and 12 months included ABPM, GFR, UAE and echocardiography. The results were analysed in the combined group (CG) and in according aetiology. 24 h SBP and 24 h DBP decreased in all groups 6 months post-intervention and did not change further. Cure of HT was observed in 35% and 29% of ASC patients at 6 and 12 months respectively; and in 58% of FMD patients. Failure rate at 12 months was 48% in ASC against 25% in FMD. The mean GFR in CG was higher 12 months after intervention. The increase in GFR was noted in 45% of patients, the decrease in 25% of patients at 12 months. Normal values of UAE were found in 71% of patients, pre- and post-intervention alike. Mean LVMI and number of patients with LVH in CG decreased already during the initial 6 months post-intervention and did not change further. In conclusion, correction of RAS leads to cure of or improved control of hypertension in the majority of the patients with FMD, but in the ASC group in about half of cases no BP cure or improvement was seen. The renal function was improved or stable in two-thirds of patients after revascularization. Successful renal revascularization was followed by regression of LVH, which was evident within 6 months post-intervention.