Studies on the Biogenesis and Metabolism of Norepinephrine in Patients With Pheochromocytoma*

Sjoerdsma, Albert; Leeper, Lemuel C.; Terry, Luther L.; Udenfriend, Sidney

doi:10.1172/jci103793

Cited by 62 publications

(12 citation statements)

References 19 publications

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“…These studies have contributed to our knowledge of sympathetic nerve function. Attempts to measure norepinephrine turnover rate in man have been rather limited, employing DLnorepinephrine-'H (4, 9, 10) and dopamine-"C (11). For this reason it was decided to carry out The Journal of Clinical Investigation Volume 47 1968 further studies, particularly in regard to the question of an abnormality in norepinephrine metabolism in essential hypertension.…”

Section: Introductionmentioning

confidence: 99%

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

DeQuattro¹,

Sjoerdsma²

1968

J. Clin. Invest.

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A B S T R A C T Intravenous administration of tritium-labeled 3,4-dihydroxyphenylalanine (dopa) to human subjects resulted in the labeling of endogenous catecholamines and vanillylmandelic acid (VMA). Determination of the changes in specific activity of these compounds with time in fractional collections of urine and in cardiac biopsies from patients undergoing corrective cardiac surgery permitted estimation of apparent turnover rates. The average half-time of the exponential decline in specific activity of labeled urinary norepinephrine was about 8 hr and that of VMA was 11-16 hr in five normal subjects. No significant differences from normal were observed in eight patients with essential hypertension. The average half-life of norepinephrine was only 5 hr in cardiac patients undergoing surgery, and the levels and rate of decline of cardiac norepinephrine specific activity correlated well with the exponential phase of the urinary disappearance curve. There were significant effects of treatment with alpha-methyltyrosine, reserpine, and pargyline hydrochloride on the labeling and apparent turnover rates of norepinephrine and VMA; the effects noted were consistent with known actions of these three drugs. It is suggested that the technique used is a suitable means of assessing "over-all" catecholamine metabolism in man, particulary if combined with

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Section: Introductionmentioning

confidence: 99%

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

DeQuattro¹,

Sjoerdsma²

1968

J. Clin. Invest.

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“…The results of this study confirm the fact that normal as well as hypertensive subjects excrete many times as much VMA as NE in their urine. Increased excretion of NM, the only other NE metabolite believed to occur in urine in large quantities (6,13), has also been suggested as a possible means of diagnosing pheochromocytoma (6). Up to this time, however, the procedures for demonstrating NM and WI in urine have been inadequate for routine use (14).…”

Section: Resultsmentioning

confidence: 99%

The Diagnosis of Pheochromocytoma by Determination of Urinary 3-Methoxy,4-Hydroxymandelic Acid*†

Gitlow¹,

Mendlowitz²,

Khassis³

et al. 1960

J. Clin. Invest.

118

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In 1957, Armstrong, McMillan and Shaw demonstrated a metabolite of epinephrine (E) and norepinephrine (NE) in normal human urine (2, 3). This substance, 3-methoxy,4-hydroxymandelic acid (VMA, for vanillylmandelic acid), was excreted in abnormally large amounts in three patients with pheochromocytomas (3). Recent studies of sympathomimetic amine metabolism (Figure 1) (4-7) suggested that the urinary excretion of the degradation products of E and NE, such as their 3-methylated derivatives (M and NM respectively) and VMA, might exceed E and NE excretion by some 10-or 20-fold. The diagnosis of pheochromocytoma might therefore be facilitated by analysis of urine for these phenolic compounds.Armstrong, Shaw and Wall's chromatographic technique for determination of urinary VMA (8, 9) was modified and used for the quantitative determination of VMA excretion in the urines of OH

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“…Studies of catecholamine metabolism have demonstrated that urinary excretion of metanephrine and VMA generally exceeds the excretion of NE and E by 10-fold to 100-fold (26)(27)(28)(29)(30)(31). Thus in Cases 1, 2 and 5 the presence of markedly elevated levels of urinary VMA as contrasted to NE and E indicates that normal metabolic pathways were in operation.…”

Section: Discussionmentioning

confidence: 97%

“…Sjoerdsma et at. (29) indicated that the turnover rate for NE in some pheochromocytomas may be more rapid than in others. Data are not yet adequate for drawing conclusions.…”

Section: Discussionmentioning

confidence: 99%

Urinary Excretion of Norepinephrine, Epinephrine and 3-Methoxy-4-Hydroxymandelic Acid by Children With Neuro-Blastoma*†

Voorhess

Gardner

1961

The Journal of Clinical Endocrinology & Metabolism

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This study concerns the urinary excretion of norepinephrine (NE), cpinephrine (E) and 3-methoxy-4-hydroxymandelic acid (VMA) in 5 infants and children with neuroblastomata and 1 child with a ganglioneuroblastoma. Prior to treatment by surgery, radiation or chemotherapy (alone, or in combination), 3 of the patients excreted increased amounts of both NE and VMA. One patient excreted slightly increased amounts of NE, but VMA output was very high. Another had a normal output of VMA, but a greatly elevated output of NE. In the remaining patient, both NE and VMA excretions were normal. The output of epinephrine was not increased in any of the cases. In general, clinical improvement following therapy was associated with a drop in the urinary excretion of NE and VMA. With progression of the disease, the excretion of these compounds again increased. These findings indicate that there may be biochemical differences among neuroblastomata, even though the tumors may be of similar histologic appearance. Delineation of these differences may be important in diagnosis, prognosis and treatment.T HE neuroblastoma is one of the most common malignant tumors of infancy and childhood. It generally results in a rapid downhill course and death in a few months, despite treatment by surgery, chemotherapy,

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Studies on the Biogenesis and Metabolism of Norepinephrine in Patients With Pheochromocytoma*

Cited by 62 publications

References 19 publications

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

Catecholamine turnover in normotensive and hypertensive man: effects of antiadrenergic drugs

The Diagnosis of Pheochromocytoma by Determination of Urinary 3-Methoxy,4-Hydroxymandelic Acid*†

Urinary Excretion of Norepinephrine, Epinephrine and 3-Methoxy-4-Hydroxymandelic Acid by Children With Neuro-Blastoma*†

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