18-Oxocortisol (18-oxoF) is a derivative of cortisol (F) that is produced by aldosterone synthase (CYP11B2). The potential for this steroid as a biomarker for differentiating patients with aldosterone-producing adenoma (APA) from those with idiopathic hyperaldosteronism (IHA) has not been examined.We measured 18-oxoF, aldosterone, and F in plasma from adrenal vein sampling (AVS) of patients with primary aldosteronism. We compared 18-oxoF levels and 18-oxoF/F ratios for their potential to differentiate APA from IHA.This study measured 18-oxoF, F, and aldosterone in AVS obtained from patients with unilateral APA (14 cases) or bilateral IHA (seven cases, 14 samples total) using liquid chromatography-tandem mass spectrometry and RIA analyses.The levels of 18-oxoF and the ratios of 18-oxoF/F, before and after ACTH stimulation, were significantly higher in blood-draining APA than in those from the contralateral adrenal glands and from adrenal glands with IHA.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.
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 (18oxoF) and 18-hydroxycortisol could contribute to the clinical differentiation between aldosteronoma and bilateral hyperaldosteronism in 234 patients with primary aldosteronism, including computed tomography (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. 18oxoF and 18-hydroxycortisol were measured using liquid chromatography tandem mass spectrometry. Receiver operating characteristic analysis of 18oxoF discrimination of adenoma from hyperplasia demonstrated sensitivity/specificity of 0.83/0.99 at a cut-off value of 4.7 ng/dL, compared with that based on 18-hydroxycortisol (sensitivity/specificity: 0.62/0.96). 18oxoF levels above 6.1 ng/dL or of aldosterone >32.7 ng/dL were found in 95 of 113 patients with aldosteronoma (84%) but in none of 121 bilateral hyperaldosteronism, 30 of whom harbored CT-detectable unilateral nonfunctioning nodules in their adrenals. In addition, 18oxoF levels below 1.2 ng/dL, the lowest in aldosteronoma, were found 52 of the 121 (43%) patients with bilateral hyperaldosteronism. Further analysis of 27 patients with CT-undetectable micro aldosteronomas revealed that 8 of these 27 patients had CT-detectable contralateral adrenal nodules, the highest values of 18oxoF and aldosterone were 4.8 and 24.5 ng/dL, respectively, both below their cut-off levels indicated above. The peripheral plasma 18oxoF concentrations served not only to differentiate aldosteronoma but also could serve to avoid unnecessary surgery for nonfunctioning adrenocortical nodules concurrent with hyperplasia or microadenoma.
Sexual differentiation of brain structure and function is dependent on the hormonal environment during perinatal life. Recently, some studies have found the greatest aromatase activity in brain areas associated with sexual differentiation and sexual behavior, namely the hypothalamic and limbic structures. We have characterized the developmental and anatomical patterns of aromatase of aromatase activity in brains of fetal, neonatal, infantile and adult rats of both sexes. Aromatase activities in slices of brain were assayed by measuring the amount of 3H2 O formed during the conversion of [1β-3H] androstenedione to estrogen. We have demonstrated major changes of the aromatase activity in the brain with age. Aromatase activities of both sexes reached peak values in the hypothalamus-preoptic area (HPOA) at least 3 days before birth. Thereafter, the activities declined to 3 weeks after birth. We have found the greatest amount of aromatase activity in HPOA and amygdala of both sexes. Aromatase activities in HPOA and amygdala of neonatal male rat were higher than adult male rat. The hippocumpus, thalamus, pituitary, cerebral cortex and cerebellum all contained negligible aromatase activity. And, we studied HPOA in detail, aromatase activities in preoptic area and anterior part of hypothalamus were twice higher than that in posterior part of hypothalamus. Aromatase activity reached peak values at the critical period of the sexual differentiation of the brain in HPOA and amygdala, associated with sexual behavior and sexual differentiation. We have reported that aromatase activity was regulated by androgen. We suggested that aromatization didn't occure effectively in female rat, owing to scarcity of androgen, which was activator and substrate of aromatase. Consequently, we considered that aromatase in the brain played an important role in the sexual differentiation of the brain for musculinization or defeminization at the critical period.
