A pheochromocytoma is a catecholamine-producing tumor of the chromaffin cells, which typically occurs in the adrenal glands. It causes a permanent or paroxysmal hypertension. Diagnosis is made by measurements of Katecholaminabbauprodukten in blood and urine. Imaging methods, especially ultrasound, CT or MRI, can be helpful in tumor localization. The treatment consists, as far as possible in the removal of the tumor. Drug therapy for blood pressure control includes an alpha-receptor blockade, which is usually combined with a beta-receptor blockade.
(See illustration of the adrenal function.)
A pheochromocytoma is a catecholamine-producing tumor of the chromaffin cells, which typically occurs in the adrenal glands. It causes a permanent or paroxysmal hypertension. Diagnosis is made by measurements of Katecholaminabbauprodukten in blood and urine. Imaging methods, especially ultrasound, CT or MRI, can be helpful in tumor localization. The treatment consists, as far as possible in the removal of the tumor. Drug therapy for blood pressure control includes an alpha-receptor blockade, which is usually combined with a beta-receptor blockade. (See illustration of the adrenal function.) The secreted catecholamines are norepinephrine, epinephrine, dopamine and dopa in varying amounts. About 90% of pheochromocytomas in the adrenal cortex, but they can also be located in other derived from neural crest tissues. Among the possible locations include the following: Para ganglia of the sympathetic chain Retroperitoneal along the course of the aorta carotid body in Zuckerkandl organ (at the aortic bifurcation) prostatitis brain pericardium dermoid cysts pheochromocytomas occur with equal frequency in both sexes in the adrenal medulla before, are in 10% of cases bilaterally (in children in 20% of cases) and are malignant in <10% of cases. Of the extra-adrenal tumors 30% are malignant. Although pheochromocytomas may occur at any age, there is a peak age between 20 and 40 years. Ee is believed that about 25 to 30% are due to mutations stem cells. Pheochromocytomas vary in size, are on average but with a diameter of 5-6 cm. They weigh 50 to 200 g, but there have also been described in tumors weighing several kilograms. They are rarely so large that you can scan them or symptoms due to pressure or displacement occur. Regardless of the histology of the tumor is considered benign if it does not penetrate the capsule and no metastases are detected. Of these, there are exceptions. In general, larger tumors are more likely to be malignant. Pheochromocytomas can occur where other endocrine tumors (parathyroid carcinoma or medullary thyroid carcinoma) are present or may develop in the following also with the syndrome of familial multiple endocrine neoplasia (MEN) type 2A and 2B. Pheochromocytomas develop in 1% of patients with neurofibromatosis (Crohn von Recklinghausen) and, together with hemangioblastomas and renal cell carcinomas such. As occur in von Hippel-Lindau syndrome. Familial pheochromocytoma occurring and tumors of the carotid body can be caused by mutation of the enzyme succinate dehydrogenase, as well as by the genes that are responsible for others, recently described signaling molecules. The symptoms and complaints hypertension, which occurs paroxysmal in 45% of patients, is the leading symptom. About 1/1000 of all hypertensive patients has a pheochromocytoma. General symptoms and signs are tachycardia sweating orthostatic hypotension tachypnea Cold and clammy skin severe headache angina palpitations nausea and vomiting stomach pain blurred vision dyspnea Paresthesias constipation destruction feeling Paroxysmal attacks can by palpation of the tumor, location changes, abdominal compression or massage, introduction of anesthesia, emotional trauma, Beta blockade sole (which paradoxically increases blood pressure by blocking beta-mediated vasodilatation) or by urination (when the tumor in the bladder is located) to be triggered. In elderly patients have a significant weight loss and a persistent hypertension indicate a pheochromocytoma. Except during a paroxysmal attack the results of the physical examination except for the high blood pressure are normal. The retinopathy and cardiomegaly are often less severe than the degree of hypertension might suggest, however no specific Katecholaminkardiomyopathie can occur at any time. Diagnosis free metanephrines in plasma or metanephrines in urine Imaging methods of thorax and abdomen, (CT or MRI) with a positive diagnosis of catecholamine possibly nuclear imaging with 123I-metaiodobenzylguanidine (MIBG) A pheochromocytoma is occurring in patients with typical symptoms or particularly sudden, severe or intermittent hypertension, for which there is no other explanation, suspected. In urine and blood, high concentrations can be detected by Katecholaminabbauprodukten. Blood tests The determination of free metanephrines in plasma achieved a sensitivity of 99%. This study has a better sensitivity than measuring circulating adrenaline or noradrenaline as the Plasmametanephrine, unlike adrenaline and noradrenaline (which are released intermittently), are constantly increasing. Greatly increased norepinephrine in the plasma makes the diagnosis very wahrscheinlich.Urinuntersuchungen metanephrines in urine are somewhat less specific than in plasma, but the sensitivity is approximately 95%. Two or three normal test results hypertensive while the patient to make the diagnosis very unlikely. The accuracy of the measurement of adrenaline and noradrenaline in the urine is comparable to that of Metanephrines. The major metabolites of adrenaline and noradrenaline in the urine are the metanephrines, Vanillylmandelic (VMA) and homovanillic acid (HVA). Healthy people excrete only very small amounts of these substances. Normal values ??for 24 h are as follows: Free adrenaline and noradrenaline <100 micrograms (<582 nM) Whole metanephrine <1.3 mg (<7.1 .mu.mol) VMA <10 mg (<50 .mu.mol) HVA <15 mg (< 82.4 .mu.mol) When pheochromocytoma urinary excretion of adrenaline and noradrenaline and their metabolites increases intermittently. Increased excretion of these substances can also in other diseases (eg. B. neuroblastoma, coma, dehydration, sleep apnea syndrome), under extreme stress, in patients who are treated with Rauwolfia alkaloids, methyldopa or catecholamines, or after the intake of food, large amounts of vanillin (especially in the presence of renal failure) auf.Andere functional tests the blood volume is reduced and there may arise false high values ??of Hb and hematocrit. Hyperglycemia, glycosuria, or a diabetes mellitus with increased fasting blood glucose levels as well as elevated levels of free fatty acids and glycerol may occur. The plasma insulin mirror are pathologically low for blood glucose levels. After removal of the pheochromocytoma, may be especially in patients who were treated with oral antidiabetic agents, hypoglycaemia. Provocation tests with histamine or tyramine are hazardous and should not be used. Glucagon (0.5-1 mg fast i.v. administered) generated in normotensive patients with pheochromocytoma a rise in blood pressure> 35/25 mmHg within 2 minutes. but this test is usually unnecessary. Phentolamine must lie ready to end a triggered hypertensive crisis. Tips and risks provocation tests with histamine or tyramine are hazardous and should not be performed. Screening tests are preferred to provocation tests. In general, the measurement of Methanephrinen should be used in plasma or urine as a screening test. Provocation tests, however, should be avoided. In patients with elevated plasma catecholamines can be a suppression test using oral clonidine or i.v. Pentolinium perform, but this is rarely necessary. Imaging method for tumor location are normally carried out in patients with pathologic screening tests. The investigations should consist of a CT scan or MRI of the thorax and abdomen (with and without contrast). When using isotonic contrast agent conducting a Adrenorezeptorblockade is not necessary. FDG-PET has also been particularly successful in patients with succinate – dehydrogenase used mutations. The repeated sampling after catheterization of the vena cava in various places, including the adrenal veins to determine the Plasmakatecholaminkonzentrationen may contribute to tumor location: in the samples of veins draining the tumor, there is an abrupt increase in norepinephrine concentration. The ratio of norepinephrine: Can be adrenaline for the identification of a small adrenal Katecholaminquelle important, but it is now rarely necessary to determine this ratio. The use of radiolabeled drugs for nuclear medicine plays a role in the localization diagnosis of pheochromocytoma. MIBG is the most widely used compound; will be 0.5 mCi 123I-MIBG i.v. injected, and then the measurements are performed on days 1, 2 and 3. In contrast to 85% of pheochromocytomas takes healthy adrenal tissue very little of this isotope on. The presentation is usually successful only if the tumor is large enough to get noticed in the CT or MRI, but it can be useful, ectopic or multifocal herd as a source of catecholamines to detect. 131I-MIBG is a less sensitive alternative. It should be sought (in neurofibromatosis z. B. Café-au-lait spots) for evidence of an associated genetic disorder. A screening assay for MEN by serum calcitonin determination and depending on the clinical symptoms and by collection of additional laboratory parameters should be performed. Many centers perform routine genetic testing, especially if the pheochromocytoma includes the sympathetic ganglia Para. Monitoring of therapy of hypertension with a combination of alpha blockers and beta-blockers Surgical removal of the tumor with perioperative blood pressure control and volume status Surgical removal is the treatment of choice. Preparing for surgery hypertension must by means of a combination therapy of beta-blockers and alpha blockers (usually 20-40 mg p.o. phenoxybenzamine 2 times daily and propranolol 20-40 mg p.o. 3 times a day) can be brought under control. Beta blockers should not be used without conducting adequate alpha blockade. Some alpha blockers such. As doxazosin, can be equally effective, but more easily digestible. The volume of budget should be balanced. Tips and risks should be given alpha blockers first, then beta-blockers. Unhindered beta-blockade can cause a paradoxical increase in blood pressure by blocking the beta-mediated vasodilation. The most effective and safest preoperative alpha blockade with phenoxybenzamine 0.5 mg / kg i.v. 1 time performed in 0.9% saline over 2 hours daily starting 3 days before the operation., But oral phenoxybenzamine is very effective, are available as long 7 to 14 days for the balancing of the volume in general. Nitroprusside may be infused as part of a pre- or intraoperative hypertensive crisis. In the detection or already on the suspicion of a bilateral tumor appearance (eg. As in patients with MEN) is sufficient hydrocortisone administration (100 mg i v. 2 times daily), which is before and administered during surgery, an acute Glukokortikoidmangel prevented due to a bilateral adrenalectomy. Most pheochromocytomas can be removed laparoscopically. Blood pressure should be monitored continuously by means of an invasive measurement. Close monitoring of the volume of household is just as necessary. The introduction of anesthesia should be used with drugs that have done (eg. As Thiobarbiturates) no arrhythmogenic potential. A continuation of the anesthesia with enflurane is recommended. During surgery, sudden increases in blood pressure with Phentolamininjektionen of 1-5 mg iv should or Nitroprussidinfusionen (2-4 mcg / kg / min) and tachyarrhythmias with propranolol 0.5-2 mg i.v. be treated. If muscle relaxants are used, you should for drugs that provoke histamine release, decide. Atropine should not be used preoperatively. Preoperative blood transfusion (1-2 units) may be given prior to removal of the tumor in anticipation of a loss of blood when the blood pressure was preoperatively well under control, a low sodium diet should postoperatively to increase blood volume, are complied with. Should develop hypotension, norepinephrine 4-12 mg / l may be the drug of choice in a dextrose solution. Some patients whose hypotension responds poorly to the administration of norepinephrine, can range from 100 mg hydrocortisone iv benefit, but usually only adequate hydration is necessary. Malignant metastatic pheochromocytoma should be treated with alpha blockers and beta-blockers. It is possible that the tumor is growing very slowly, and the survival time by is very long. However, the blood pressure can be controlled even with very rapid tumor growth. 131I-MIBG may help reduce symptoms in patients with residual disease. Metyrosine, a tyrosine hydroxylase inhibitor can be used to reduce the catecholamine production in patients whose blood pressure is difficult to control. Radiation therapy can reduce bone pain. Chemotherapy is rarely effective, but the most common treatment plan that has been tried is the combination of cyclophosphamide, vincristine, and dacarbazine. Recent data have shown some promising results with the chemotherapy drug temozolomide and targeted therapy with sunitinib. Conclusion Hypertension may be constant or episodic. In urine and blood, high concentrations of Katecholaminabbauprodukten (typically metanephrine) can be detected. Tumors should be localized with imaging tests, sometimes with radiolabeled compounds. A combination of alpha blockers and beta blockers will be given if the tumor removal is still pending.