The relationship between calcitrophic hormones and blood pressure has been investigated in 583 elderly subjects who were untreated for hypertension. Univariate analysis demonstrated that serum parathyroid hormone, calcitriol, albumin and calcium were correlated significantly with mean blood pressure (r = +0.15, +0.10, +0.14 and +0.11, respectively), as were body mass index and age (r = +0.19 and +0.10, respectively). Parathyroid hormone also was correlated positively with both age and calcitriol (r = +0.34 and +0.15, respectively) and negatively with plasma calcium and albumin (r = -0.09 and -0.09, respectively). Multivariate analysis demonstrated that when allowing for age and body mass index, parathyroid hormone and calcitriol were both significant independent determinants of the mean blood pressure. When other independent variables were included in the analysis, parathyroid hormone but not calcitriol remained a significant predictor of mean blood pressure. This study has demonstrated a weak but significant relationship between blood pressure and calcitrophic hormones in a group of elderly people. The data are consistent with the hypothesis that hypertension may be due in part to calcium deficiency.

Background Plasma-free normetanephrine and metanephrine (metanephrines) are the recommended biomarkers for testing of pheochromocytoma and paraganglioma (PPGL). This study evaluated the status of harmonization of liquid chromatography-tandem mass spectrometry-based measurements of plasma metanephrines and methoxytyramine and clinical interpretation of test results. Methods 125 plasma samples from patients tested for PPGLs were analyzed in 12 laboratories. Analytical performance was also assessed from results of a proficiency-testing program. Agreement of test results from different laboratories was assessed by Passing-Bablok regression and Bland-Altman analysis. Agreement in clinical test interpretation based on laboratory specific reference intervals was also examined. Results Comparisons of analytical test results by regression analysis revealed strong correlations for normetanephrine and metanephrine (R ≥ 0.95) with mean slopes of 1.013 (range 0.975–1.078), and 1.019 (range 0.963–1.081), and intercepts of −0.584 (−53.736 to 54.790) and −3.194 (−17.152 to 5.933), respectively. The mean bias between methods was 1.2% (−11.6% to 16.0%) for metanephrine and 0.1% (−18.0% to 9.5%) for normetanephrine. Measurements of 3-methoxytyramine revealed suboptimal agreement between laboratories with biases ranging from −32.2% to 64.0%. Interrater agreement in test interpretation was >94% for metanephrine and >84% for normetanephrine; improvements in interrater agreement were observed with use of harmonized reference intervals, including age-specific cut-offs for normetanephrine. Conclusions Analytical methods for metanephrines are well harmonized between laboratories. However, the 16% disagreement in test interpretation for normetanephrine suggests use of suboptimal method-dependent reference intervals for clinical decision-making for this metabolite. Improved analytical methods and reference interval harmonization are particularly required for 3-methoxytyramine.

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Keywords: pilot study; plasma free metanephrines; plasma total metanephrines; proficiency testing.The diagnosis of pheochromocytoma is based on the quantitation of O-methylated metabolites of catecholamines (1, 2). Several studies have reported high sensitivity of free metanephrines in plasma for assessing the presence of tumour (1). Measurement of plasma total metanephrines (plasma freeqplasma sulphoconjugated metanephrines) has also been proposed as a diagnostically sensitive assay (3). Therefore, an increasing number of laboratories have developed *Corresponding author: Dr. Eric Grouzmann, PhD, Division de Pharmacologie et Toxicologie Cliniques, University Hospital of Lausanne, Lausanne, Switzerland Phone: q41-21-3140741, Fax: q41-21-3144266, E-mail: eric.grouzmann@chuv.ch assays for free and total metanephrines using different analytical procedures including immunoassays (4, 5), high-performance liquid chromatography (HPLC) coupled to amperometric or coulometric detection (6) and liquid chromatography-tandem mass spectrometry (LC-MS) methods (7). Each laboratory is supposed to establish its own reference values and to perform quality control measurements (QCs) with each set of analyses. The internal QC samples usually are prepared by each laboratory and should include plasma samples spiked with known concentrations of both metanephrine (MN) and normetanephrine (NMN). Participation in an external quality assessment scheme (EQAS) allows direct comparisons between all laboratories that measure free and total metanephrines. In this context, the variability of the upper reference limit for free metanephrines reported in the literature is relatively large. For NMN the range varies from 0.6 to 1.4 nmol/L, and for MN it varies from 0.3 to 0.85 nmol/L (1, 2, 8). However, the upper reference limits for total metanephrines are better defined (3, 9, 10). The analytical procedure for the quantitation of metanephrines in plasma is not the only reason for this variability. The characteristics of the control population may also differ between different studies. The absence of a universal calibrator that could be used by all laboratories performing such measurements encouraged us to establish an EQA program for plasma free and total metanephrines. A similar program already exists for metanephrines and catecholamines in urine. The purpose of this letter is to present the results of a pilot study aimed at implementing a proficiency survey for all laboratories measuring plasma free and/or total metanephrines.We selected 10 centres that routinely measure free and/or total plasma metanephrines for diagnosis of pheochromocytoma. Three analytical methods were used. Immunoassays (1 participant), HPLC with electrochemical detection (ECD) (8 participants) including amperometry, coulometry, coularray and LC-MS (1 participant). All but one laboratory, which used an RIA commercial kit method, used in-house methods. Calibrators and internal quality control samples were manufactured using spiked serum pools with standard dilutions of Sigma...