Primary aldosteronism due to unilateral aldosterone-producing adenoma (APA) is a surgically curable form of hypertension. Bilateral APA can also be surgically curable in theory but few successful ...cases can be found in the literature. It has been reported that even using successful adrenal venous sampling (AVS) via bilateral adrenal central veins, it is extremely difficult to differentiate bilateral APA from bilateral idiopathic hyperaldosteronism (IHA) harbouring computed tomography (CT)-detectable bilateral adrenocortical nodules. We report a case of bilateral APA diagnosed by segmental AVS (S-AVS) and blood sampling via intra-adrenal first-degree tributary veins to localize the sites of intra-adrenal hormone production. A 36-year-old man with marked long-standing hypertension was referred to us with a clinical diagnosis of bilateral APA. He had typical clinical and laboratory profiles of marked hypertension, hypokalaemia, elevated plasma aldosterone concentration (PAC) of 45.1 ng dl(-1) and aldosterone renin activity ratio of 90.2 (ng dl(-1) per ng ml(-1 )h(-1)), which was still high after 50 mg-captopril loading. CT revealed bilateral adrenocortical tumours of 10 and 12 mm in diameter on the right and left sides, respectively. S-AVS confirmed excess aldosterone secretion from a tumour segment vein and suppressed secretion from a non-tumour segment vein bilaterally, leading to the diagnosis of bilateral APA. The patient underwent simultaneous bilateral sparing adrenalectomy. Histopathological analysis of the resected adrenals together with decreased blood pressure and PAC of 5.2 ng dl(-1) confirmed the removal of bilateral APA. S-AVS was reliable to differentiate bilateral APA from IHA by direct evaluation of intra-adrenal hormone production.
OBJECTIVE:The measurement of plasma aldosterone concentration (PAC) and renin activity (PRA) or active renin concentration (ARC) is clinically important not only for detection of primary ...aldosteronism but also for the selection of antihypertensive agents to treat patients successfully. However, it has taken approximately 7 days for clinicians to get the results. Of late, we developed the novel rapid non-RIA assays of PAC and ARC, which are measurable in 10 minutes. This study is intended to investigate the utility and accuracy of this new methods.
DESIGN AND METHOD:Both PAC and ARC were simultaneously measured by chemiluminescent enzyme immunoassay (CLEIA) system machine with their specific monoclonal antibodies and were automatically washed by the immobilized magnetic particles. We retrospectively compared RIA-assayed PAC, PRA, ARC and LC-MS/MS-measured PAC with CLEIA-measured PAC and ARC in 290 patients with aldosterone producing adenoma (APA, n = 100), bilateral idiopathic hyperaldosteronism (IHA, n = 100) and essential hypertension (EH, n = 90).
RESULTS:CLEIA-measured PAC were significantly correlated with RIA-assayed PAC (y = 0.9846 x + 2.5708, Spearmanʼs r = 0.9072, P < 0.0001), and also significantly correlated with LC-MS/MS PAC (y = 1.039 x + 8.0, Spearmanʼs r = 0.997, P < 0.0001). Rapid CLEIA-measured ARC with the lower detection limit of 0.25 pg/mL, which is very small as compared to that of 2 pg/mL in conventional RIA-assayed ARC, were significantly correlated with RIA-assayed ARC (y = 1.0103 x + 0.9156, Spearmanʼs r = 0.8166, P < 0.0001), and also significantly correlated with RIA-assayed PRA (Spearmanʼs r = 0.8091 y = 4.4331 x + 0.4456, P < 0.0001). ARR-A and ARR-C of APA patients were 206 ± 21.7 and 64.5 ± 5.1 (Mean ± SEM), respectively. ARR-A and ARR-C of IHA patients were 42.8 ± 4.7 and 13.2 ± 0.9, and those of EH patients 15.4 ± 3.1 and 3.0 ± 0.5, respectively.
CONCLUSIONS:Our ten minutes CLEIA-assay of PAC and ARC were proved to be accurate and might be clinically very useful, not only for detecting primary aldosteronism but also for choosing antihypertensive drugs in EH patients. Clinicians will be able to get the simultaneously measured results during patients’ waiting for a short time at their first visits.
OBJECTIVE:The measurement of plasma aldosterone (PAC) and renin concentration (ARC) or activity (PRA) is useful for selecting antihypertensive agents as well as diagnosing primary aldosteronism (PA) ...in hypertensive patients. However, it takes several days to get results when measured by radioimmunoassay and development of more rapid assay has been long expected. In the present study, we characterized recently developed fully-automated chemiluminescent enzyme immunoassay (CLEIA) for PAC and ARC, which can be measured simultaneously in 10 minutes and 20 seconds, and clinical validation of their diagnostic abilities for detecting PA patients from hypertensive patients was also performed in this study.
DESIGN AND METHOD:We performed clinical validation of diagnostic ability of this newly developed assay-based screening of 125 patients with primary aldosteronism (75 aldosteronoma (APA) and 50 bilateral hyperplasia (BHA)) from 97 patients with essential hypertension (EH).The newly developed assays of both PAC and ARC adopted antibody-immobilized magnetic particles, called MAGRAPID with abilities of quick aggregations and dispersions.
RESULTS:Results of this novel measurements were significantly correlated with both radioimmunoassay measurements (PAC, ARC and PRA) and liquid chromatography-tandem mass spectrometry measurements (PAC). The analytical sensitivity of this particular novel ARC measurement was 0.1 pg/mL, which was better than that of radioimmunoassay (2.0 pg/mL). The ARC values measured by CLEIA were below than 2.0 pg/mL in 28.8% of all patients (52.0%, 44.0% and 3.1% in those with unilateral APA, BHA and EH, respectively). Using Bland-Altman plot analysis with the mass-spectrometry measurement, both bias and limits of agreement with 95% confidence interval of the automated PAC assay were smaller than those of the radioimmunoassay, indicating smaller systemic errors in the novel measurement. The ratio of PAC-over-ARC of 11.2 (ng/dL per pg/mL) provided 80.8% sensitivity and 94.9% specificity as a cut-off for differentiating primary aldosteronism from essential hypertension.
CONCLUSIONS:This novel measurement is expected to be clinically reliable alternatives for conventional radioimmunoassay and to provide better throughput and cost-effectiveness in diagnosis of hyperaldosteronism from larger number of hypertensive patients in clinical settings.
Scintillation characteristics of CsPbCl3 single crystals Kobayashi, M.; Omata, K.; Sugimoto, S. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2008, Letnik:
592, Številka:
3
Journal Article
OBJECTIVE:Definitive diagnosis of primary aldosteronism requires a long process, including adrenal venous sampling, which currently represents the only reliable method to distinguish unilateral from ...bilateral diseases. 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.
DESIGN AND METHOD:This study included 234 primary aldosteronism patients including CT-detectable aldosteronoma (APA) (n = 113) and bilateral hyperaldosteronism (BHA) (n = 121), all of whom underwent adrenal venous sampling. All aldosteronomas were surgically resected and their diagnosis was both clinically and histopathologically confirmed. Both 18-oxocortisol and 18-hydroxycortisol were measured using liquid chromatography tandem mass spectrometry.
RESULTS:ROC analysis of 18-oxocortisol discrimination of adenoma from hyperplasia demonstrated sensitivity/specificity of 0.83/0.99 at a cutoff value of 4.7 (ng/dL), compared to that based upon 18-hydroxycortisol (sensitivity/specificity0.62/0.96). 18-oxocortisol levels above 6.1 ng/dL and/or of aldosterone above 32.7 ng/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 1.2 ng/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 peripheral 18-oxocortisol and aldosterone were 4.8 and 24.5 ng/dL, respectively, both below their cutoff levels indicated above.
CONCLUSIONS: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.(Figure is included in full-text article.)Receiver operating characteristic (ROC) analysis of patients with APA compared to those with BHA as control and distribution plot analysis. A, B, C and D depict ROC curves to analyze the diagnostic value of respectively peripheral 18-oxocortisol (18oxoF), 18-hydroxycortisol (18OHF), aldosterone and aldosterone-renin activity ratio (ARR), to discriminate APA from BHA. E, F, G and H show respectively the distribution of peripheral 18-oxo-cortisol, 18-hydroxycortisol, aldosterone and aldosterone-renin activity ratio in APA and BHA.
OBJECTIVE:Adrenal venous sampling (AVS) has been well known to play pivotal roles in clinical differential diagnosis of unilateral aldosterone producing adenoma (APA) from bilateral idiopathic ...hyperaldosteronism (IHA). However, it is also true that a central vein AVS or c-AVS which collects the blood from right and left central adrenal veins can by no means discriminate bilateral APA from BHA. There have been no published studies reporting the reliable clinical differential diagnosis between bilateral APA and IHA, especially IHA cases with bilateral non-functioning adenomas (NFA), which has been considered practically impossible in clinical differential diagnosis. As an attempt to this clinical dilemma, segmental AVS (S-AVS), which could evaluate segmental effluents from adrenal tributary veins, has been recently developed.
DESIGN AND METHOD:We have performed S-AVS in these patients above following C-AVS, via the insertion of a microcatheter in up to three intra-adrenal first-degree tributary veins on bilateral adrenals.
RESULTS:S-AVS did enable us to evaluate the intra-adrenal localization of corticosteroidogenesis. These data did indicate that S-AVS should be performed in the PA patients who had increased aldosterone levels in bilateral central vein and demonstrated space occupying lesions in the bilateral adrenals in order to avoid bilateral adrenalectomy or long lasting medical treatment toward persistent PA. In addition to the situations above, we have administere S-AVS to the following patients; those who had clinically suspected APA but not sufficiently high lateralization indexes according to the results of C-AVS, very young ones with higher clinical probability of recurrence and those who could benefit from partial adrenalectomy by demonstrating the sites of specific steroidogenesis. However, it is also entirely true that S-AVS is more expensive, time-consuming and labor-intensive compared to C-AVS.(Figure is included in full-text article.)The angiography during S-AVS (A, B), the coronal CT image (C), and the data in external iliac vein (EIV), each central vein (1, 4) and each tributary vein (2, 3, 5, 6) of 66 year-old male patient with bilateral APAs.
CONCLUSIONS:We should carefully select the candidate patients who should undergo S-AVS, which will give a benefit to themselves by demonstrating intra-adrenal steroidogenesis for a safer preserving adrenalectomy.
Primary aldosteronism affects ≈5% to 10% of hypertensive patients and has unilateral and bilateral forms. Most unilateral primary aldosteronism is caused by computed tomography-detectable ...aldosterone-producing adenomas, which express CYP11B2 (aldosterone synthase) and frequently harbor somatic mutations in aldosterone-regulating genes. The cause of the most common bilateral form of primary aldosteronism, idiopathic hyperaldosteronism (IHA), is believed to be diffuse hyperplasia of aldosterone-producing cells within the adrenal cortex. Herein, a multi-institution cohort of 15 IHA adrenals was examined with CYP11B2 immunohistochemistry and next-generation sequencing. CYP11B2 immunoreactivity in adrenal glomerulosa harboring non-nodular hyperplasia was only observed in 4/15 IHA adrenals suggesting that hyperplasia of CYP11B2-expressing cells may not be the major cause of IHA. However, the adrenal cortex of all IHA adrenals harbored at least 1 CYP11B2-positive aldosterone-producing cell cluster (APCC) or micro-aldosterone-producing adenomas. The number of APCCs per case (and individual APCC area) in IHA adrenals was significantly larger than in normotensive controls. Next-generation sequencing of DNA from 99 IHA APCCs demonstrated somatic mutations in genes encoding the L-type calcium voltage-gated channel subunit α 1-D (CACNA1D, n=57; 58%) and potassium voltage-gated channel subfamily J-5 (KCNJ5, n=1; 1%). These data suggest that IHA may result from not only hyperplasia but also the accumulation or enlargement of computed tomography-undetectable APCC harboring somatic aldosterone-driver gene mutations. The high prevalence of mutations in the CACNA1D L-type calcium channel provides a potential actionable therapeutic target that could complement mineralocorticoid blockade and inhibit aldosterone overproduction in some IHA patients.
PDF
![[OP.6D.06] THE ACCURATE NOV...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0263-6352/small "[OP.6D.06] THE ACCURATE NOVEL TEN MINUTES MEASUREMENTS OF ALDOSTERONE AND ACTIVE RENIN CONCENTRATIONS WILL BE USEFUL AT OUTPATIENT OFFICE")
