Essential hypertension with low conjugated catecholamines imitates pheochromocytoma.
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Biomedical subjects
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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.
From a total of 61 referred hypertensive patients, 21 were clinically suspected of pheochromocytoma but in none was this diagnosis confirmed. Instead we found nine of the 21 patients had surges of conjugated dopamine during hyperadrenergic periods unaccounted for by rise in norepinephrine (NE) or epinephrine (E). Overall, essential hypertensive (EH) patients had in plasma (ng/ml) higher conjugated dopamine (DA) (2.3 +/- 0.2 vs 1.0 +/- 0.1, p less than 0.01), increasing with age (p less than 0.01), lower conjugated NE + E (0.6 +/- 0.1 vs 1.2 +/- 0.2, p less than 0.01), and higher free E (p less than 0.007), lower urinary free DA and total DA but higher free NE + E excretions (each p less than 0.05) than 24 control subjects. Following the DA surges, a short-lived urinary overflow of total DA occurred. The patients with DA surges were older, had a higher incidence of low conjugated NE + E (less than 0.23 ng/ml), a higher proportion of arterial free DA, and higher venous baseline conjugated plasma DA than the rest of the patients. Patients with low conjugated NE + E had in turn higher plasma DA concentrations at several regional sampling sites than patients with normal conjugated NE + E. High conjugated DA in EH probably results from pulsatile DA surges leading to a rise of baseline plasma conjugated DA. In the short run DA pulses can result in temporary alpha- and beta-adrenergic actions of huge arterial free DA concentrations prior to DA conjugation; in the long run the excessive high affinity DA conjugation may take preference to the lower affinity NE and lowest affinity E conjugation and free E increases. Both result in an acute or chronic increase of sympathetic tone.
Continuous subcutaneous insulin infusion (CSII) is one of the ways to control blood glucose for prolonged periods. This study was undertaken to establish the long-term feasibility and efficacy of CSII with patient self-management. Patients were instructed to maintain their calorie and carbohydrate intake. Basal infusion of insulin, representing 50% of the total pre-CSII dose, was supplemented by boluses of insulin based on carbohydrate intake for each meal. With this type of regimen, blood glucose and M-values were easily normalized during the physician-directed periods. This study demonstrated that near-normalization of blood glucose, M-values, and glycosylated hemoglobin was maintained after a 1 1/2-yr period of patient self-management. We attributed this successful management in part to the protocol used, in which boluses were related solely to carbohydrate intake while basal insulin was adjusted according to fasting blood glucose. The chronic normalization of blood glucose resulted in improvement of platelet function as witnessed by responsiveness to antiaggregating (PGE1) and aggregating (epinephrine) agents. An improvement was noticed in doppler measurement of ankle-arm blood pressure and a near-normalization of nerve latency and conductivity was observed.
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