Plasma metanephrines offer improved efficacy for the diagnosis of pheochromocytoma. Less variability in response to external factors may favor plasma metanephrines in the screening for this disease. Arch Intern Med. 2000;160:2957-2963
Background: Pheochromocytoma is a rare cause of hypertension resulting from increased catecholamine secretion. We aimed to develop a method to measure unconjugated plasma normetanephrine (NMN) and metanephrine (MN) without interference from acetaminophen, a widely prescribed drug for headaches.
Methods: Plasma samples were obtained from 48 subjects (23 males, 25 females; mean age, 49 ± 14 years; hypertension, n = 37) under resting conditions. Following extraction on solid-phase cation-exchange columns, unconjugated metanephrines were analyzed by HPLC with electrochemical detection and with 4-hydroxy-3-methoxybenzylamine as an internal standard. Catecholamines were measured by HPLC.
Results: The assays were linear up to 2000 pg for NMN and for MN. Intraassay imprecisions (CVs) were 4.7% for NMN and 7.0% for MN, and the interassay CV was 12% for both NMN and MN. The limit of detection was 11 fmol for NMN and 17 fmol for MN. Ingestion of acetaminophen or its addition to plasma did not interfere with the MN peaks. Plasma NMN and MN were positively correlated (r = 0.52 and 0.49, respectively; P <0.01 for both) with the respective catecholamines. Plasma NMN (r = 0.27; P = 0.02) but not MN positively correlated with age, whereas only plasma catecholamines (and not metanephrines) were positively correlated (P <0.05) with diastolic blood pressure.
Conclusions: This sensitive MN assay is not affected by simultaneous acetaminophen medication, and reveals a correlation of metanephrines with plasma and urinary catecholamines and age but not with blood pressure.
STINGL, HARALD, WOLFGANG RAFFESBERG, PETER NOWOTNY, WERNER WALDHÄ USL, AND MICHAEL RODEN. Reduction of plasma leptin concentrations by arginine but not lipid infusion in humans. Obes Res. 2002; 10:1111-1119. Objective: We examined short-term effects of arginine infusion on plasma leptin in diabetic and healthy subjects. Research Methods and Procedures: Arginine stimulation tests were performed in C-peptide negative type 1 [DM1; hemoglobin A 1c ; 7.3 Ϯ 0.3%], hyperinsulinemic type 2 diabetic (DM2; 7.6 Ϯ 0.7%), and nondiabetic subjects (CON; 5.4 Ϯ 0.1%). Results: Fasting plasma leptin correlated linearly with body mass index among all groups (r ϭ 0.61, p ϭ 0.001). During arginine infusion, peak plasma insulin was lower in DM1 than in DM2 (p Ͻ 0.05) and CON (p Ͻ 0.01). Plasma leptin decreased within 30 minutes by ϳ11% in DM1 (p Ͻ 0.001), DM2 (p Ͻ 0.01), and CON (p Ͻ 0.005), slowly returning to baseline thereafter. Plasma free fatty acids (FFAs) were higher in DM1 (0.6 Ϯ 0.1 mM) and DM2 (0.6 Ϯ 0.1 mM) than in CON (0.4 Ϯ 0.1 mM, p Ͻ 0.05) and transiently declined by ϳ50% (p Ͻ 0.05) at 45 minutes in all groups before rebounding toward baseline. To examine the direct effects of FFAs on plasma leptin, we infused healthy subjects with lipid/heparin and glycerol during fasting, and somatostatin-insulin (ϳ35 pM) -glucagon (ϳ90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by ϳ25% (p Ͻ 0.05) during 540 minutes without any difference between the high and low FFA conditions. Discussion: Arginine infusion transiently decreased plasma leptin concentrations both in insulin-deficient and hyperinsulinemic diabetic patients, indicating a direct inhibitory effect of the amino acid but not of insulin or FFAs.
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