Phaeochromocytoma and Other Catecholamine-Producing Tumours

Winkler, Hans; Smith, A D

doi:10.1007/978-3-642-65249-3_20

Cited by 19 publications

(18 citation statements)

References 163 publications

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“…This may indicate that catecholamine is not necessarily stored with ATP in a constant molar ratio in adrenal chromaffin granules. In fact, an extremely wide range of values (4-7-35-1:1) of the ratio were reported for human phaeochromocytoma granules (Winkler & Smith, 1972). Furthermore, it was reported that the ratio of noradrenaline to ATP in the large dense-cored vesicles of sympathetic nerves varied from 12 to 18 or 19 and in some cases 50, depending upon the localization of the nerve vesicles (Lagercrantz, Fried & Dahlin, 1975).…”

Section: Discussionmentioning

confidence: 99%

Time course of release of catecholamine and other granular contents from perifused adrenal chromaffin cells of guinea‐pig.

Ito¹

1983

The Journal of Physiology

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SUMMARY1. Experiments were carried out to investigate the time course of the release of catecholamine, dopamine-,8-hydroxylase (DBH) and adenine nucleotides from isolated chromaffin cells of guinea-pig adrenal gland.2. When the isolated chromaffin cells were incubated with medium containing acetylcholine (ACh) (0-1 mM), veratridine (0-1 mM) or scorpion (Leiurus quinquestriatus) venom, (10 ,ug/ml.), catecholamine was released into the medium. Catecholamine secretion induced by veratridine or scorpion venom was inhibited by tetrodotoxin (1 gM) but not by atropine (0-1 mM) plus hexamethonium (041 mM). On the other hand, the secretary response to ACh was abolished by the cholinergic blocking drugs but not by tetrodotoxin.3. DBH was released together with catecholamine into the medium in which cells were suspended with these drugs. The ratio of catecholamine (n-mole) to DBH activity (n-mole/hr) appearing in the supernatant was 7-08 + 055, 6-60 + 0X27 and 8X91 + 0 47 for ACh, veratridine and scorpion venom, respectively. These values were close to that found in the lysate of chromaffin granules obtained from guinea-pig adrenal glands (7-37 + 0-39).4. The application of ACh or veratridine to perifused chromaffin cells was found to cause a parallel increase in catecholamine and DBH secretion in the perifusion medium without corresponding amounts of phenylethanolamine-N-methyltransferase leakage. However, DBH secretion tended to last for a longer period than catecholamine secretion.5. Adenine nucleotides were released from perifused chromaffin cells together with catecholamine, by ACh and veratridine. ATP added to the perifusion medium was metabolized to ADP and AMP, of which the ratio (ATP, 21-6 %; ADP, 34 %; AMP, 17-9 %) was close to those of adenine nucleotides released from the cells.6. The secretion ofadenine nucleotides induced by both secretagogues ceased much faster than the catecholamine secretion, so that the molar ratio of catecholamine to adenine nucleotides was gradually increased during and after stimulation. 7. The results indicate that catecholamine secretion is accompanied with a simultaneous release of DBH and ATP from adrenal chromaffin cells. Therefore, it is suggested that the delayed output of DBH, unlike catecholamine secretion, in perfused adrenal glands results from the presence of a diffusion barrier for this protein. The releasable secretary granules of isolated chromaffin cells are suggested to be heterogeneous with respect to the ratio of catecholamine to ATP.

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Section: Discussionmentioning

confidence: 99%

Time course of release of catecholamine and other granular contents from perifused adrenal chromaffin cells of guinea‐pig.

Ito¹

1983

The Journal of Physiology

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“…15 Engelman and Sjoerdsma 16 showed that tyramine injection into patients with pheochromocytoma caused increased excretion of urinary catecholamines and their metabolites, an effect that persisted for several days after tumor removal. In keeping with these findings, we found that high plasma NE values linger for about 1 week after complete tumor resection.…”

mentioning

confidence: 99%

Blood pressure regulation in pheochromocytoma.

et al. 1982

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SUMMARY Two sets of studies were performed in 13 patients with prored adrenal pheochromocytoma to test the hypothesis that the sympathetic nervous system (SNS) Is active and might contribute to the hypertensire state. Similar studies were performed in 15 additional patients considered to have essential hypertension. In the first set, 13 patients with pheochromocytoma were subjected to head-up tilt to assess the activity of the SNS. This maneuver decreased diastolic blood pressure in only two; heart rate increased appropriately in all except one. Changes in plasma noreplnephrine (NE) were variable and did not correlate with changes in blood pressure (BP) and heart rate (HR).In the second set, 10 patients with pheochromocytoma were given a single oral dose of clonldine (03 mg) to evaluate what role, if any, the SNS might contribute to the hypertensive state. Fifteen patients with essential hypertension were studied similarly for comparison. Clonidlne produced significant decreases in BP and HR but left plasma renln activity unchanged in both groups. In essential hypertension, the cardiovascular responses were accompanied by significant reductions in plasma NE. By contrast, plasma NE was unchanged in patients with pheochromocytoma, despite similar reductions in BP and HR. These results suggest that the sympathetic reflexes are intact in pbeochromocytoma, and that much of the hypertension associated with these tumors may be related to increased sympathetic activity. T HE hypertension that accompanies pheochromocytoma has generally been ascribed to the excessive circulating catecholamines released from the tumor. However, recent studies have demonstrated a marked discrepancy between the height of arterial pressure and the prevailing plasma catecholamine concentration; 1 in fact, some of these patients may have long periods of normotension despite high circulating catecholamines. Lack of correlation between blood pressure (BP) and plasma catecholamine levels has been attributed to varying responsiveness of the cardiovascular system dependent on several factors, including the rate of catecholamine inactivation (by uptake mechanisms and enzymatic degradation), the extent to which catecholamines diffuse and reach target cells, the inherent reactivity of vascular smooth muscle, and finally to receptor sensitivity.One possibility that has received little attention is the active participation of the sympathetic nervous system (SNS) in BP control; although it has been assumed that sympathetic activity could be depressed in pheochromocytoma by the high catecholamine levels, this possibility has not been critically assessed in man. We therefore planned two sets of studies to assess that hypothesis. In the first, we used head-up tilt to determine the activity of the SNS. In the second, we administered clonidine (a centrally-acting antihypertensive agent that inhibits neurally-mediated catecholamine release) to evaluate, from changes in heart rate (HR), BP, plasma norepinephrine (NE) and plasma renin activity (PRA), the role of ...

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“…Pheochromocytomas are not innervated, and other mechanisms are responsible for the release of their CA. 34 The Kultschitzky cells of the bronchi and the gut which arise from the neural crest synthesize S." Chromaffin cells, which arise from the neural crest, also have been shown to produce S and VIP.26 Sporadic pheochromocytomas contain small amounts of S, whereas the familial variety contain much more." Even patients with higher concentrations of tumor S, however, usually do not have urinary 5HIAA levels above n0rma1.l~ Although our patient had a sporadic pheochromocytoma, his preoperative urinary 5HIAA was above normal and his tumor was rich in S, as demonstrated by chemical analysis and immunocytochemistry.…”

Section: Cancer July 15 1987mentioning

confidence: 99%

An unusual pheochromocytoma associated with an androgen secreting adrenocortical adenoma. Evaluation of its polypeptide hormone, catecholamine, and enzyme characteristics

Sparagana¹,

Feldman²,

Molnar³

1987

Cancer

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Our patient had a left suprarenal mass. His blood pressure was normal, but his urinary catecholamines (CA), vanillylmandelic acid (VMA), total metanephrines (TMn) and 5-hydroxyindolacetic acid (SHIAA) were elevated. In addition, he had elevated, nonsuppressible urinary 17-ketosteroids (17KS) and androsterone, but his urinary 17-hydroxycorticoids (170HCS) and free cortisol were normal, as were his plasma cortisol and ACTH. After resection of the suprarenal mass, the patient's urinary hormone values reverted to normal. The mass contained a pheochromocytoma and an adrenocortical adenoma. The pheochromocytoma was unusual in that it contained very little norepinephrine (NE) and dopamine (DA) and an abundance of epinephrine (E) despite normal enzyme concentrations. Electron micrographs showed primarily E granules with few of the NE-type. The immunoperoxidase histochemical stains for vasoactive intestinal peptide (VIP) and serotonin (S) were strongly positive. The patient's blood pressure may have been normal because his pheochromocytoma secreted E, VIP, or S. The associated adrenocortical adenoma produced no symptoms and was probably coincidental.

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Phaeochromocytoma and Other Catecholamine-Producing Tumours

Cited by 19 publications

References 163 publications

Time course of release of catecholamine and other granular contents from perifused adrenal chromaffin cells of guinea‐pig.

Time course of release of catecholamine and other granular contents from perifused adrenal chromaffin cells of guinea‐pig.

Blood pressure regulation in pheochromocytoma.

An unusual pheochromocytoma associated with an androgen secreting adrenocortical adenoma. Evaluation of its polypeptide hormone, catecholamine, and enzyme characteristics

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