Showing papers by "Pierre Larochelle published in 1981"
TL;DR: The association of subnormal conjugated plasma NE and/or E with moderately elevated plasma NE + E and a more frequent pseudopheochromocytoma presentation may result from inadequate conjugation, and hence inactivation of NE and or E.
Abstract: SUMMARY The correlation between the degree of conjugation of plasma noreplnephrine (NE) and epinepbrine (E) and the clinical features of sympathetic hyperactivity was studied in 38 essential hypertensive patients from a referral population biased toward pheochromocytoma (19 of them suspected of this diagnosis on clinical grounds). The patients were separated into two groups: 15 with subnormal plasma conjugated NE + E, i.e., below 0.23 ng/ml (Group 1), and 23 patients above this limit (Group 2). Patients clinically suspected of pheochromocytoma represented 93% of the patients in Group 1 but only 21% in Group 2.Group 1 patients, compared to those of Group 2, had: 1) higher baseline plasma free NE + E (0.51 ± 0.07 ng/ml vs 0.30 ± 0.04 ng/ml, p < 0.02); 2) an increase in plasma free NE + E in response to stressful sampling (148% ± 59%, p < 0.05 vs 58% ± 30%), and a more pronounced response (p < 0.05) to glucagon administration; 3) higher free NE + E and DA in the regional samples received during catheterization while conjugated NE and/or E were usually absent; and 4) a higher spread between maximum and minimum blood pressure and a higher maximum pulse rate recorded as well as the index of sympathotonia. All patients combined had the 'maximum pulse rate correlated negatively (p < 0.005) with conjugated NE + E, but positively (p < 0.005) with free NE + E. The clinical and biochemical similarity to pheochromocytoma was particularly striking in some Group 1 patients who had a selective defect in E conjugation; some of them had a history of surgical exploration for the lesion, without result.The association of subnormal conjugated plasma NE and/or E with moderately elevated plasma NE + E and a more frequent pseudopheochromocytoma presentation may result from inadequate conjugation, and hence inactivation of NE and/or E. Excessive free catecholamines would account for the clinical symptoms and for tbe fact that the patients are well controlled by treatment with beta-adrenerglc blocking agents, either alone or in combination with a-blockers. Awareness of tbe existence of this variety of essential hypertension can obviate unnecessary surgery for wrongly suspected pheochromocytoma.
50 citations
TL;DR: The glucagon‐induced catecholamine test can be false‐positive in hyperadrenergic essential hypertensive patients with abnormally low conjugated NE + E, and therefore, if plasma free NE and E are measured and found not to rise this type of false‐ positive result can be eliminated.
Abstract: In more than half of 67 patients suspected of having pheochromocytoma, glucagon stimulation increased plasma free norepinephrine (NE) and epinephrine (E) 50% or more, with rising blood pressure or pulse rate; only three patients, however, harbored a pheochromocytoma. A low degree of catecholamine conjugation accounts for most of the false-positive results. In patients with low conjugated NE + E there was a greater rise in free NE + E and free E as well as in pulse rate after glucagon stimulation than in those with normal levels of conjugated NE + E. Glueagon-sensuive adenylate cyclase was found in pheochromocytomas but not in afunctional adrenocortical adenomas. After sham administration of glucagon, there were rises in blood pressure but not in free NE or E in four patients. The glucagon-induced catecholamine test can be false-positive in hyperadrenergic essential hypertensive patients with abnormally low conjugated NE + E. Saline alone in a sham glucagon test in susceptible patients raises systolic blood pressure and pulse rate, and therefore, if plasma free NE and E are measured and found not to rise this type of false-positive result can be eliminated.
Clinical Pharmacology and Therapeutics (1981) 29, 687–694; doi:10.1038/clpt.1981.96
12 citations
01 Jan 1981
TL;DR: The previous studies suggested that sulfoconjugation occurs during passage of catecholamines through the blood in man and dog and the platelets appear to be an important source of PST responsible for the sulfconjugation that takes place in blood.
Abstract: Sulfoconjugation of catecholamines is a recently recognized yet poorly explored mechanism of inactivation of catecholamines (CA) in man. The current determinations of norepinephrine (NE) and epinephrine (E) measure only the free fraction of plasma NE and E (approximately 20% of the total) while the conjugated fractions accounting for the remaining approximately 80% of circulating NE and E can be determined only after hydrolysis by which free NE and E are liberated from the conjugated form (Buu & Kuchel, 1977). The process of conjugation is dependent on the type of catecholamine, its affinity to, activity and degree of saturation of the sulfoconjugating enzyme phenolsulfotransferase (PST) and its accessibility to the sulfoconjugating sites; sulfate concentration does not appear to represent a limiting factor of sulfoconjugation (Wettering et al., 1979). Our previous studies suggested that sulfoconjugation occurs during passage of catecholamines through the blood in man (Kuchel et al., 1980) and dog (Unger et al., 1980). The platelets appear to be an important source of PST (Hart et al., 1979) responsible for the sulfoconjugation that takes place in blood.
5 citations
TL;DR: The absolutely and relatively decreased plasma conjugation E in patients with E exceeding NE (without difference in conjugated NE) is a preliminary indication that a selective sulfoconjugating defect of E results in plasma E higher than NE in accordance with the hyper- β-adrenergic features of their hypertension.
Abstract: Hypertensive patients with elevated and hyperresponsive plasma norepinephrine and epinephrine (NE + E) associated with low conjugated NE + E were previously identified by determination of the sum of NE + E. Because of their excessive E but not NE responses to glucagon and also hypertension corresponding to E excess, we explored whether an elevated unconjugated E resulting from a selective E conjugation defect could be obscured by the sum of NE + E. We found that nine patients with elevated E (reflected by the normal 4:1 ratio of plasma NE to E reversed in favor of E), had, when compared to 31 patients with plasma NE exceeding E:1) lower plasma conjugated E (mean 0.03 vs 0.27 ng/ml, p less than 0.01), lower degree of E conjugation (8 vs 51%, p less than 0.01), and a higher maximum systolic (p less than 0.05), pulse pressure (p less than 0.02) and higher pulse rates (p less than 0.04), but no differences in the unconjugated and conjugated proportions of plasma NE; and 2) an absence of conjugated E throughout the circulation and relative preponderance of E over NE at sampling points close to the peripheral venous blood (p less than 0.05). The absolutely and relatively decreased plasma conjugated E in patients with E exceeding NE (without difference in conjugated NE) is a preliminary indication that a selective sulfoconjugating defect of E results in plasma E higher than NE in accordance with the hyper-beta-adrenergic features of their hypertension. Epinephrine, a circulating hormone, is more dependent on conjugated E reflect better this defect than those measuring the sum of NE and E.
2 citations