Progress Report 2013

Progress Report 2013: Project 5: Novel diagnostic biomarkers of excessive aldosterone secretion in patients with aldosteronomas

Background

Primary aldosteronism is the most frequent cause of secondary hypertension and it can be caused by unilateral or bilateral adrenal disease. Adrenal venous sampling (AVS) is considered to be the method of choice to establish the source of excessive aldosterone secretion in patients with primary aldosteronism (PA). This project focuses on the further development of AVS with emphasis on its duration and accuracy. In order to shorten the time of AVS, rapid tests such as the adrenochrome-based colorimetric (ABC) test were to be developed and compared to immediate cortisol measurements. To aid the clinician in the decision whether the AVS was actually successful, the utility of plasma metanephrines as an alternative analyte to cortisol was to be tested. For the demonstration of a lateralized aldosterone secretion, in both the adrenal vein samples, the amount of aldosterone per metanephrine should be evaluated against the amount of aldosterone per cortisol. In addition, steroid profiling was planned for detecting altered steroidogenesis in tumorous adrenal tissue. The results would have immediate impact on clinical standard operating procedures.

Achievements

A number of assays were shown to be faster than the immediate determination of cortisol and included the ABC test, a rapid epinephrine immunoassay, cross-reactivity of a metamphetamine drug test with catecholamines, an ascorbic acid strip test, and the tetrazolium blue staining of steroid hormones. However, these assays were proven to render a lower accuracy rate than automated cortisol determinations. Currently, a cell line is being tested which expresses beta-adrenoceptors linked to an cAMP-specific fluorescence signal and it shows acceptable sensitivity in picking-up the typical epinephrine concentrations in adrenal venous blood. We have shown that metanephrine provides a superior analyte over cortisol for assessing selectivity of adrenal vein sampling during procedures without cosyntropin. In addition, we have successfully established an LC-MS/MS method for steroid profiling in fluids.

Completion of objectives

1. We have evaluated the ABC test and other rapid assays and found that these tests are not suitable for clinical routine because of their inacceptable low accuracy.

2. We were successful in demonstrating that plasma free metanephrine in adrenal venous blood provides a new biomarker with superior characteristics to cortisol in AVS studies during the diagnostic work-up of primary aldosteronism. This provides proof of principle for future prospective randomized studies to provide concrete outcome data. We have also established steroid proflling methodology with immediate applicability to our banked AVS samples and numerous other KFO projects.