Adrenal venous sampling is currently the only reliable method to distinguish unilateral from bilateral diseases in primary aldosteronism. In this study, we attempted to determine whether peripheral plasma levels of 18-oxocortisol and 18-hydroxycortisol could contribute to the clinical differentiation between aldosteronoma and bilateral hyperaldosteronism in 234 patients with primary aldosteronism, including CT-detectable aldosteronoma (n=113) and bilateral hyperaldosteronism (n=121), all of whom underwent CT and adrenal venous sampling. All aldosteronomas were surgically resected and the accuracy of diagnosis was clinically and histopathologically confirmed. 18-oxocortisol and 18-hydroxycortisol were measured using liquid chromatography tandem mass spectrometry. ROC analysis of 18-oxocortisol discrimination of adenoma from hyperplasia demonstrated sensitivity/specificity of 0.83/0.99 at a cutoff value of 4.7ng/dL, compared to that based upon 18-hydroxycortisol (sensitivity/specificity: 0.62/0.96). 18-oxocortisol levels above 6.1ng/dL and/or of aldosterone above 32.7ng/dL were found in 95 of 113 aldosteronoma patients (84%) but in none of 121 bilateral hyperaldosteronism, 30 of whom harbored CT-detectable unilateral nonfunctioning nodules in their adrenals. In addition, 18-oxocortisol levels below 1.2ng/dL, the lowest in aldosteronoma, were found 52 out of the 121 (43%) patients with bilateral hyperaldosteronism. Further analysis of 27 patients with CT-undetectable micro aldosteronomas revealed that eight of these 27 patients had CT-detectable contralateral adrenal nodules, the highest values of 18-oxocortisol and aldosterone were 4.8 and 24.5ng/dL, respectively, both below their cutoff levels indicated above. The peripheral plasma 18-oxocortisol concentrations served not only to differentiate aldosteronoma, but also could serve to avoid unnecessary surgery for nonfunctioning adrenocortical nodules concurrent with hyperplasia or microadenoma.

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The 18-oxoF levels and ratios of 18-oxoF/F in AVS samples can be a clinically useful biomarker for differentiating APA from IHA and for determining the localization or lateralization of APA in patients with primary aldosteronism.

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Our findings suggest that adipose tissue acts as an endocrine organ, with CYP17 and CYP19 activity playing an essential role in sex steroid hormone biosynthesis.