SEARCH · PubMed Health
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Pheochromocytoma is an infrequent cause of hypertension. In spite of its rarity, pheochromocytoma has assumed notorious importance because or a wide variety of clinical features associated with this syndrome. Hypertension remains the most important clinical lead. The presence of other features, such as severe headache, perspiration, palpitations or orthostatic hypotension, makes the diagnosis of pheochromocytoma likely. The diagnosis of this condition can be made with greater certainty than that of any other form of secondary hypertension. Pharmacologic tests are no longer used for evaluation purposes. Biochemical tests are the most important aids to diagnosis, provided highly specific methods are used to determine the levels of urinary catecholamines or their metabolites. Interference by various drugs should be avoided. Most of the pheochromocytomas are found in the abdomen, predominantly in the adrenals. Successful outcome of surgery depends critically on adequate preoperative preparation of the patient with adrenergic blocking drugs and proper intraoperative care. Surgery should only be performed in an institution with experience in treating these tumors. Invasive localizing procedures could be dangerous in patients with pheochromocytoma and are best avoided. Medical therapy proves to be quite successful for those patients who are unable or unwilling to undergo surgery and for those with demonstrated malignant tumor. The postoperative course in most instances is uneventful. The physician should be aware of familial forms of pheochromocytomas and screen all the hypertensive members of the patient's family for the presence of this condition. Pheochromocytoma, with its multiple facets, presents a challenge to the clinician; however, with prompt diagnosis and proper treatment, pheochromocytoma can often be cured. The improved management of patients with this potentially lethal condition is the result of better knowledge of biochemical pharmacology, improved preoperative, surgical and postoperative care.
Long-term epidemiological and laboratory studies were carried out in a kindred with familial pheochromocytoma associated with von Hippel-Lindau disease. Thirteen members were affected by the syndrome and the trait appears to be transmitted in an autosomal dominant fashion. Of 13 patients, 7 had pheochromocytoma alone. Of the remaining six patients, one had pheochromocytoma combined with von Hippel-Lindau disease, four had pheochromocytoma with retinal disease only, and a single patient had a retinal lesion without pheochromocytoma. In four patients, pheochromocytoma antedated the development of retinal lesions. Ten members also had mild hypercalcemia without accompanying elevations of PTH in the 4 patients in whom this was determined. In all, hypercalcemia was corrected with removal of tumors, and no patient had a return of hypercalcemia in the absence of recurrent increases in urinary catecholamines. The clinical presentations in 12 patients varied markedly, as did their urinary excretion rates of norepinephrine, epinephrine and their metabolites. However, an analysis of the data revealed significant correlations not previously described between the urinary excretion of free catecholamines (norepinephrine plus epinephrine), blood pressure, the free catecholamine content of the tumor and the age of the patient. Urinary excretion of free norepinephrine plus epinephrine appear to be decreased with advancing age (p less than 0.001). Both systolic and diastolic blood pressures and the age of the patient were inversely correlated (p less than 0.01). A significant inverse relationship between the tumor content of free catecholamines and the age of the patients was, although to a lesser degree, also present (p less than 0.05). As a whole, the size of the tumors and their norepinephrine content were not correlated. We present a concept that, in familial pheochromocytoma, the metabolism of catecholamines is altered by the process of aging, and that this change modifies the clinical presentations of the disease.
Using a sensitive and specific radioenzymatic assay, the plasma norepinephrine (NE) concentration was measured in seven patients with pheochromocytoma, one patient with bilateral adrenal medullary hyperplasia, one patient with a retroperitoneal paraganglioma, and two patients undergoing bilateral adrenalectomies for palliation of metastatic breast carcinoma. Surgical manipulation of the pheochromocytomas resulted in striking increases in plasma NE concentration with concomitant increases in blood pressure. There were either small changes or no changes in the patients' plasma NE and blood pressure during resection of the normal adrenal glands, the adrenal glands with medullary hyperplasia, or the retroperitoneal paraganglioma. Plasma dopamine-beta-hydroxylase (DBH) was measured in one patient with pheochromocytomas and the patient with medullary hyperplasia. There was no change in plasma DBH in either patient, supporting the concept that exocytosis is not the primary mechanism for catecholamine secretion from pheochromocytomas. It was also noted that enflurane is an excellent general anesthetic for the resection of pheochromocytomas, and that sodium nitroprusside (rather than phentolamine) may be the agent of choice for the management of the hypertensive episodes that occur during surgical manipulation of pheochromocytomas.
Three biochemical tests for the diagnosis of pheochromocytoma were evaluated in 24 patients with proved tumors and 40 patients whose clinical picture was suspect but who had no evidence of the disease. Measurement of resting, supine plasma catecholamines (by radioenzymatic assay) was more useful than either 24-hour urinary vanillylmandelic acid (VMA) or metanephrines or both. In only one of 23 patients with pheochromocytoma were plasma catecholamines within the range of those in patients without pheochromocytoma, as compared with urinary VMA in 11 of 22, urinary metanephrines in five of 22 and both metabolites in three of 22. These studies reaffirm the value of plasma catecholamines in the diagnosis of pheochromocytoma and indicate that urinary catecholamine metabolites are less useful. The poor correlation between the height of arterial pressure and circulating levels of catecholamines suggests that the regulation of arterial pressure in pheochromocytoma is complex.
The biogenesis of C19- and C21-steroids has been studied in tissue slices of a paraganglioma, of a pheochromocytoma and of human adrenal cortex using radioactive steroids. Slices of paraganglioma as well as of pheochromocytoma metabolise 17-hydroxyprogesterone to cortisone, cortisol, 11-deoxycortisol and testosterone. The rate of formation of these steroids, however, by the two tumours is 8--15 times less than that in normal adrenal cortex tissue. After incubation of dehydroepiandrosterone with tissue slices of paraganglioma and pheochromocytoma, 7alpha-hydroxydehydroepiandrosterone, 11beta-hydroxy-4-androstene-3,17-dione and 4-androstene-3,17-dione were found as metabolites; testosterone was converted by both tissues to 4-androstene-3,17-dione. 17-Hydroxypregnenolone was converted to a small extent (1.7%) to dehydroepiandrosterone by slices of paranganglioma. These results show that enzymes of steroid biosynthesis (hydroxylases, oxidoreductases, delta4(-5)-isomerases, C17(-20)-desmolases) are present in both paraganglioma and pheochromocytoma.
As pheochromocytoma sometimes is accompanied by medullary thyroid carcinoma (in the sense of multiple endocrine adonomatosis type II = Sipple-Syndrome), serum calcitonin (CT) was measured by radioimmunoassay in 4 patients with pheochromocytoma. Before extirpation of the adreno-medullary tumor, serum CT was distinctly increased to 3 and 30 ng/ml in 2 of 4 patients, respectively. After removal of the tumor, serum CT was normal in the patients and pentagastrin stimulation produced no exaggerated CT response. In hydrochloric acid extracts from the two corresponding pheochromocytoma tissues, immunoreactive-Calcitonin (IR-CT) was detected, the concentrations amounting 1 and 4 ng/mg wet tissue. These findings suggest that hypercalcitonism in patients with pheochromocytoma cannot always be ascribed to the thyroid, i.e. increased calcitonin levels do not necessarily indicate a medullary carcinoma of this organ.
The feasibility of differentiating patients with pheochromocytoma from other hypertensive patients by measuring urinary excretion rates of norepinephrine during sleep, a period of physiologic suppression of norepinephrine release, was investigated. The mean excretion rates of norepinephrine in 248 normal subjects and in 109 patients with essential hypertension were 1.03 +/- 0.03 and 1.12 +/- 0.06 (SEM) micrograms/hour, respectively, whereas the lowest excretion rate among the six patients with pheochromocytoma was about seven times higher. Plasma norepinephrine concentration in patients with pheochromocytoma was also consistently above the range observed in both normotensive and hypertensive subjects. CT scan correctly identified the same tumors visualized by selective arteriography. It is suggested that the usefulness of these approaches will provide simpler means of screening and detecting pheochromocytoma.
Two children, aged 14 yr, with multiple pheochromocytomas are presented. Both patients had a positive family history. In the preoperative aortographies the intra-adrenal pheochromocytomas of both patients were well visualized, but not the extra-adrenal tumors of the first case. Chlorpromazine as an adrenergic blocking agent was successfully used in the preoperative treatment. Postoperative catecholamine excretion in the first case was repeatedly slightly increased indicating residual pheochromocytoma. In addition to the bilateral adrenal pheochromocytomas, multiple islet cell adrenomas and cholecystolithiasis were revealed at the operation of the second case. After bilateral adrenalectomy and total pancreaticoduodenectomy, regular follow-up examinations were carried out for 28 months. Hyperparathyroidism and signs of possible medullary thryoid carcinoma were discovered. Thus the patient had an unique pattern of MEA syndrome.
A 17-year-old woman manifested fever, abdominal pain, headache, and hypertension caused by a solitary, benign pheochromocytoma. She also had hypercalcemia and elevated plasma immunoreactive calcitonin levels. After removal of the pheochromocytoma, calcium and calcitonin levels returned to normal. Studies of peripheral and tumor venous blood showed no excess or ectopic parathyroid hormone secretion, but the tumor contained and secreted calcitonin. Sporadic pheochromocytoma may secrete calcitonin and cause hypercalcemia by non-parathyroid hormone-mediated mechanisms. The potential is clearly present for confusion with multiple endocrine neoplasia, type 2 (medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism).
Currently the only treatment available for inoperable pheochromocytoma is symptomatic and palliative with alpha- and beta- adrenergic blockade. Pheochromocytoma is a tumor of chromaffin tissue derived from the neural crest and closely related to other APUD (amine precursor uptake and decarboxylation) cell tumors, including those of the pancreatic islets. Streptozocin has been used with varying success in some of these tumors and therefore merited a trial in pheochromocytoma. We used streptozocin to treat two patients with inoperable pheochromocytoma; the drug failed to have any effect, either on catecholamine excretion or tumor growth.
Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented.
Patients suffering from pheochromocytoma characterized by an exclusive or almost exclusive excess of norepinephrine showed no (one patient) or only a moderate increase (two patients) in renin and aldosterone secretion. In those three patients with concomitant distinct hypersecretion of epinephrine, renin release (and aldosterone secretion except in one patient) was markedly enhanced. Similar results were obtained in a patient with excess norepinephrine and dopamine secretion. Renin release was markedly reduced in all patients during preoperative long-term alpha-adrenergic receptor blockade. With the exception of one patient, increased renin and aldosterone secretion was abolished. The results indicate that augmentation in renin release depends on the ratio of the different catecholamines secreted by the pheochromocytoma and their different effe-tiveness in stimulating beta-adrenergic receptors. Even in the presence of excess catecholamine secretion, there is evidence that renin secretion is predominantly mediated by beta receptors rather than by renal vascular alpha-adrenergic receptors. Normalization of catecholamine-induced enhanced renin release in patients with pheochromocytoma during chronic alpha-adrenergic receptor blockade supports the assumption that (alpha-) adrenergic blocking agents inhibit renin secretion distal to their blockade of specific adrenergic receptors. However, contrary to beta-adrenergic blockade, circadian rhythm of renin release seems to remain intact during alpha-adrenergic blockade.
A kindred with 2 current cases of pheochromocytoma is reported. The proband had classical features of adrenal medullary hyperfunction, in addition to Raynaud's phenomenon. After surgical removal of the right adrenal gland, containing a pheochromocytoma and a small paraganglioma, the patient was free of symptoms. The 12-year-old son of the proband was discovered to have relatively asymptomatic sustained hypertension on routine examination. Biochemical and radiological tests confirmed the diagnosis of a left adrenal pheochromocytoma, which was removed successfully.
Following the removal of a pheochromocytoma in three female patients the daily excretion of catecholamines and their metabolites was still considerably elevated for about one week. The excretion rates declined during this period with half-lives of 1.8 to 10.9 days for catecholamines and 2.1 to 4.7 days for metanephrines, vanilmandelic acid, and vanilglycol. The cumulative urinary excretion of catecholamines and their metabolites following surgical removal of the tumour was nearly as high as the catecholamine content of the pheochromocytomas. This large amount of catecholamines must have been located outside the tumour, most probably within the sympathetic nerve, where it is subject to release following physiological stimuli. Furthermore, this fact may provide an explanation for hypertensive crises in pheochromocytoma patients.
Following adrenal phlebography, obstruction of the large bowel associated with adrenergic crisis was observed in a 60 year old patient with pheochromocytoma. As in other published cases of ileus associated with pheochromocytoma, high urinary catecholamine concentrations were found in our patient and the tumor resected at surgery was large. As phlebography immediately preceded the onset of ileus and hypertensive crisis, it is postulated that angiography led to massive secretion of catecholamines, which caused the hypertensive crisis as well as the ileus. The possible mechanisms by which phlebography may lead to adrenergic crisis are discussed. It is concluded that in suspected pheochromocytoma all angiographic examinations should be carried out under simultaneous treatment with alpha-blocking agents.
In a series of 9 cases of hypertensive pheochromocytoma, the author noted in five of them abolition of the lower abdominal skin reflex on the same side as the tumour. They were in four cases suprarenal pheochromocytomas and in the fifth case an ectopic paraganglioma of Zuckerland's organ. In 3 cases, the abolished reflex became normal and equal to that on the opposite side after removal of the tumour. In two others, it remained abolished. In 4 patients, most of the other abdominal skin reflexes, expecially those, on the opposite side, very brisk before the operation, became normal afterwards. The author concludes that in cases of hypertensive pheochromocytoma, careful study of the abdominal skin reflexes may provide a useful contribution to topographic diagnosis.
The cytologic and histochemical characteristics of the tumor cells from medullary thyroid carcinoma and pheochromocytoma are described. In cell samples obtained from medullary thyroid carcinomas, amyloid deposits were detected both intracellularly and extracellularly. Medullary thyroid carcinoma cells, as well as pheochromocytoma cells, showed positive for both argentaffin and argyrophil reactions. The diagnostic significance of intracellular amyloid deposits and of positive silver and chromaffin reactions of the intracytoplasmic granules may be stressed in establishing the cytologic diagnosis of medullary thyroid carcinoma and/or pheochromocytoma.