Mass Spectrometry–Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

Eisenhofer, Graeme; Dekkers, Tanja; Peitzsch, Mirko; Dietz, Anna; Bidlingmaier, Martin; Treitl, Marcus; Williams, Tracy Ann; Bornstein, Stefan R.; Haase, Matthias; Rump, Lars Christian; Willenberg, Holger S.; Beuschlein, Felix; Deinum, Jaap; Lenders, Jacques W.M.; Reincke, Martín

doi:10.1373/clinchem.2015.251199

Cited by 128 publications

(98 citation statements)

References 42 publications

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“…[16][17][18][19][20] An interesting novel approach consists of the measurement of a selected steroid profile by mass spectrometry. 21,22 Nevertheless, additional diagnostic steps will be needed to localize potential APA.…”

Section: Hypertensionmentioning

confidence: 99%

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Heinze¹,

Fuß²,

Mulatero³

et al. 2018

Hypertension

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Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor–positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor–positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs.

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Section: Hypertensionmentioning

confidence: 99%

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Heinze¹,

Fuß²,

Mulatero³

et al. 2018

Hypertension

Self Cite

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“…Even more recently, LC-MS/MS has been used to determine both peripheral and adrenal venous "profiles" of multiple steroids in patients with APA and BAH (394,566). While such analyses are yet to find a place in the routine workup of this condition, already they have yielded important insights, including the apparent superiority of several steroids over cortisol in defining cannulation success during AVS (129), and the much higher levels of both peripheral and adrenal venous 18-oxo-cortisol levels in patients with APAs bearing somatic KCNJ5 mutations compared with APAs without (566). The latter finding is particularly interesting as it supports the concept that somatic KCNJ5 mutations cause (and are probably the predominant basis for) a phenotype that is synonymous with the ANG II-unresponsive form of APA, with excessive production of hybrid steroids now contributing to the list of other similarities (which includes predominant female gender, younger age, larger tumors, more florid PA, lack of aldosterone responsiveness to upright posture and ZF-like morphology, as discussed in section VIF).…”

Section: Figurementioning

confidence: 99%

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

Stowasser

Gordon

2016

Physiological Reviews

125

134

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In the 60 years that have passed since the discovery of the mineralocorticoid hormone aldosterone, much has been learned about its synthesis (both adrenal and extraadrenal), regulation (by renin-angiotensin II, potassium, adrenocorticotrophin, and other factors), and effects (on both epithelial and nonepithelial tissues). Once thought to be rare, primary aldosteronism (PA, in which aldosterone secretion by the adrenal is excessive and autonomous of its principal regulator, angiotensin II) is now known to be the most common specifically treatable and potentially curable form of hypertension, with most patients lacking the clinical feature of hypokalemia, the presence of which was previously considered to be necessary to warrant further efforts towards confirming a diagnosis of PA. This, and the appreciation that aldosterone excess leads to adverse cardiovascular, renal, central nervous, and psychological effects, that are at least partly independent of its effects on blood pressure, have had a profound influence on raising clinical and research interest in PA. Such research on patients with PA has, in turn, furthered knowledge regarding aldosterone synthesis, regulation, and effects. This review summarizes current progress in our understanding of the physiology of aldosterone, and towards defining the causes (including genetic bases), epidemiology, outcomes, and clinical approaches to diagnostic workup (including screening, diagnostic confirmation, and subtype differentiation) and treatment of PA.

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“…They found that median adrenal/peripheral ratios of 11-deoxycortisol, 17-OHPG, pregnenolone, androstenedione and DHEA were several times higher than those for cortisol. Eisenhofer et al subsequently reported that LC-MS/MS-based steroid profiling during AVS had higher aldosterone lateralization ratios in patients with aldosterone-producing adenoma than immunoassays and suggested that multisteroid panel by LC-MS/MS can identify patients with unilateral disease [26]. Although previous studies of steroid profiling in AVS samples of patients with PA demonstrated higher levels of 11-deoxycortisol and other steroids compared with cortisol [25,26], no comparison was made to directly compare the performance of these markers to that of cortisol in confirming catheter position in the absence of cosyntropin.…”

Section: Discussionmentioning

confidence: 99%

“…Eisenhofer et al subsequently reported that LC-MS/MS-based steroid profiling during AVS had higher aldosterone lateralization ratios in patients with aldosterone-producing adenoma than immunoassays and suggested that multisteroid panel by LC-MS/MS can identify patients with unilateral disease [26]. Although previous studies of steroid profiling in AVS samples of patients with PA demonstrated higher levels of 11-deoxycortisol and other steroids compared with cortisol [25,26], no comparison was made to directly compare the performance of these markers to that of cortisol in confirming catheter position in the absence of cosyntropin. Although cortisol is one of the most abundantly produced adrenal steroids, the lower adrenal to peripheral ratio compared with that of 11-deoxycortisol and other steroids can be explained by the relatively slower clearance of cortisol because most circulating cortisol is bound to globulin [27,28].…”

Section: Discussionmentioning

confidence: 99%

11‐Deoxycortisol may be Superior to Cortisol in Confirming a Successful Adrenal Vein Catheterization without Cosyntropin: A Pilot Study

Nilubol

Soldin

Patel

et al. 2017

Int. J. Endo. Oncol.

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aim:We aimed to compare the performance of nine adrenal steroids in confirming the correct catheter position during adrenal venous sampling (AVS) without cosyntropin in patients with primary hyperaldosteronism. materials & methods: A successful adrenal vein catheterization without cosyntropin was defined as the ratio of steroids from adrenal to peripheral veins being >3:1. AVS samples from four patients with primary hyperaldosteronism were analyzed. results: Compared with the mean ratio of cortisol without cosyntropin, the ratios of 11-deoxycortisol (p = 0.008), dehydroepiandrosterone (p = 0.01) and androstenedione (p = 0.008) were significantly higher. None of the ratios (n = 8) of cortisol from adrenal to peripheral veins exceeded 3:1, while all ratios of 11-deoxycortisol (p < 0.001) were >3. Conclusion: Cosyntropin infusion during AVS may not be necessary if 11-deoxycortisol is used to confirm catheter position. • Because imaging alone cannot reliably distinguish aldosterone-producing adenoma from commonly detected nonfunctioning adrenal nodules. Adrenal venous sampling is considered the gold standard for selecting patients who would benefit from an adrenalectomy.• There are two areas that need to be assessed from adrenal venous sampling: the position of the catheter when the samples are collected and a comparison of normalized aldosterone production from each adrenal gland.• To confirm a successful adrenal vein catheterization, a commonly used criterion is the ratio of cortisol from the adrenal vein to the peripheral vein greater than 3:1 without cosyntropin infusion.• Compared with the cosyntropin-stimulated cortisol ratio of adrenal to peripheral veins, the nonstimulated ratio can be falsely low, suggesting incorrect catheter placement occurred in approximately 50% of the samples.• Our pilot study suggests that 11-deoxycortisol is more accurate in identifying correct position of the catheter than cortisol without cosyntropin infusion. Thus, it can simplify the procedure and reduce false-negative results associated with cosyntropin infusion.For reprint orders, please contact: reprints@futuremedicine.com

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Mass Spectrometry–Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism

Cited by 128 publications

References 42 publications

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

11‐Deoxycortisol may be Superior to Cortisol in Confirming a Successful Adrenal Vein Catheterization without Cosyntropin: A Pilot Study

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