A Clinical-Radiomic Nomogram Based on Unenhanced Computed Tomography for Predicting the Risk of Aldosterone-Producing Adenoma.
He Keng,Zhang Zhao-Tao,Wang Zhen-Hua,Wang Yu,Wang Yi-Xi,Zhang Hong-Zhou,Dong Yi-Fei,Xiao Xin-Lan
Frontiers in oncology
Purpose:To develop and validate a clinical-radiomic nomogram for the preoperative prediction of the aldosterone-producing adenoma (APA) risk in patients with unilateral adrenal adenoma. Patients and Methods:Ninety consecutive primary aldosteronism (PA) patients with unilateral adrenal adenoma who underwent adrenal venous sampling (AVS) were randomly separated into training (n = 62) and validation cohorts (n = 28) (7:3 ratio) by a computer algorithm. Data were collected from October 2017 to June 2020. The prediction model was developed in the training cohort. Radiomic features were extracted from unenhanced computed tomography (CT) images of unilateral adrenal adenoma. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensions, select features, and establish a radiomic signature. Multivariable logistic regression analysis was used for the predictive model development, the radiomic signature and clinical risk factors integration, and the model was displayed as a clinical-radiomic nomogram. The nomogram performance was evaluated by its calibration, discrimination, and clinical practicability. Internal validation was performed. Results:Six potential predictors were selected from 358 texture features by using the LASSO regression model. These features were included in the Radscore. The predictors included in the individualized prediction nomogram were the Radscore, age, sex, serum potassium level, and aldosterone-to-renin ratio (ARR). The model showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.900 [95% confidence interval (CI), 0.807 to 0.993], and good calibration. The nomogram still showed good discrimination [AUC, 0.912 (95% CI, 0.761 to 1.000)] and good calibration in the validation cohort. Decision curve analysis presented that the nomogram was useful in clinical practice. Conclusions:A clinical-radiomic nomogram was constructed by integrating a radiomic signature and clinical factors. The nomogram facilitated accurate prediction of the probability of APA in patients with unilateral adrenal nodules and could be helpful for clinical decision making.
Consequences of adrenal venous sampling in primary hyperaldosteronism and predictors of unilateral adrenal disease.
Mathur Aarti,Kemp Clinton D,Dutta Utpal,Baid Smita,Ayala Alejandro,Chang Richard E,Steinberg Seth M,Papademetriou Vasilios,Lange Eileen,Libutti Steven K,Pingpank James F,Alexander H Richard,Phan Giao Q,Hughes Marybeth,Linehan W Marston,Pinto Peter A,Stratakis Constantine A,Kebebew Electron
Journal of the American College of Surgeons
BACKGROUND:In patients with primary hyperaldosteronism, distinguishing between unilateral and bilateral adrenal hypersecretion is critical in assessing treatment options. Adrenal venous sampling (AVS) has been advocated by some to be the gold standard for localization of the responsible lesion, but there remains a lack of consensus for the criteria and the standardization of technique. STUDY DESIGN:We performed a retrospective study of 114 patients with a biochemical diagnosis of primary hyperaldosteronism who all underwent CT scan and AVS before and after corticotropin (ACTH) stimulation. Univariate and multivariate analyses were performed to determine what factors were associated with AVS lateralization, and which AVS values were the most accurate criteria for lateralization. RESULTS:Eighty-five patients underwent surgery at our institution for unilateral hyperaldosteronism. Of the 57 patients who demonstrated unilateral abnormalities on CT, AVS localized to the contralateral side in 5 patients and revealed bilateral hyperplasia in 6 patients. Of the 52 patients who showed bilateral disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS for lateralization was the post-ACTH stimulation value. Factors associated with AVS lateralization included a low renin value, high plasma aldosterone-to plasma-renin ratio, and adrenal mass > or = 3 cm on CT scan. CONCLUSIONS:Because 50% of patients would have been inappropriately managed based on CT scan findings, patients with biochemical evidence of primary hyperaldosteronism and considering adrenalectomy should have AVS. The most accurate measurement for AVS lateralization was the post-ACTH stimulation value. Although several factors predict successful AVS lateralization, none are accurate enough to perform AVS selectively.
Diagnostic performance of multidetector computed tomography in distinguishing unilateral from bilateral abnormalities in primary hyperaldosteronism: comparison of multidetector computed tomography with adrenal vein sampling.
Raman Siva P,Lessne Mark,Kawamoto Satomi,Chen Yifei,Salvatori Roberto,Prescott Jason D,Fishman Elliot K
Journal of computer assisted tomography
OBJECTIVE:The management of patients with primary hyperaldosteronism (PH) varies depending on whether the unregulated aldosterone secretion localizes to a single unilateral adrenal gland, traditionally determined using adrenal vein sampling (AVS). This study seeks to determine if the performance of multidetector computed tomography (MDCT) examinations performed using the latest scanner technology can reasonably match the results of AVS, and potentially avoid AVS in some patients. MATERIALS AND METHODS:Computed tomographic scans in 56 patients with PH were independently reviewed by 2 radiologists for the presence of adrenal nodules and qualitative adrenal thickening. Results were correlated with AVS results. RESULTS:Of 35 patients with MDCT evidence of unilateral nodules, the imaging findings correctly predicted AVS localization in only 23 (65.7%) cases. When stratified by size, MDCT was accurate in only 71.4% of cases for nodules measuring 10 mm or less, and only 55.0% of cases for nodules measuring 11 to 20 mm. Of the 12 cases where MDCT did not correctly localize, AVS localized to the contralateral adrenal gland in 4 cases, whereas AVS suggested no lateralization in 8 cases. In patients with normal bilateral adrenal glands on MDCT, 2/7 (28.6%) of cases demonstrated unilateral localization on AVS, and in patients with bilateral adrenal nodules, only 3/14 (21.4%) did not demonstrate lateralization on AVS. CONCLUSIONS:Multidetector computed tomography, even when performed with the latest generation of MDCT scanners, does not offer sufficient diagnostic accuracy to replace AVS in patients with PH.
Comparison of C-arm computed tomography and on-site quick cortisol assay for adrenal venous sampling: A retrospective study of 178 patients.
Chang Chin-Chen,Lee Bo-Ching,Chang Yeun-Chung,Wu Vin-Cent,Huang Kuo-How,Liu Kao-Lang,
OBJECTIVES:To compare the performance of on-site quick cortisol assay (QCA) and C-arm computed tomography (CT) assistance on adrenal venous sampling (AVS) without adrenocorticotropic hormone stimulation. METHODS:The institutional review board at our hospital approved this retrospective study, which included 178 consecutive patients with primary aldosteronism. During AVS, we used C-arm CT to confirm right adrenal cannulation between May 2012 and June 2015 (n = 100) and QCA for bilateral adrenal cannulation between July 2015 and September 2016 (n = 78). Successful AVS required a selectivity index (cortisol/cortisol) of ≥ 2.0 bilaterally. RESULTS:The overall success rate of C-arm CT-assisted AVS was 87%, which increased to 97.4% under QCA (P = .013). The procedure time (C-arm CT, 49.5 ± 21.3 min; QCA, 37.5 ± 15.6 min; P < .001) and radiation dose (C-arm CT, 673.9 ± 613.8 mGy; QCA, 346.4 ± 387.8 mGy; P < .001) were also improved. The resampling rate was 16% and 21.8% for C-arm CT and QCA, respectively. The initial success rate of the performing radiologist remained stable during the study period (C-arm CT 75%; QCA, 82.1%, P = .259). CONCLUSIONS:QCA might be superior to C-arm CT for improving the performance of AVS. KEY POINTS:• Adrenal venous sampling (AVS) is a technically challenging procedure. • C-arm CT and quick cortisol assay (QCA) are efficient for assisting AVS. • QCA might outperform C-arm CT in enhancing AVS performance.
Anatomical Variations of the Right Adrenal Vein: Concordance Between Multidetector Computed Tomography and Catheter Venography.
Omura Kensuke,Ota Hideki,Takahashi Yuuki,Matsuura Tomonori,Seiji Kazumasa,Arai Yoichi,Morimoto Ryo,Satoh Fumitoshi,Takase Kei
Hypertension (Dallas, Tex. : 1979)
Adrenal venous sampling is the most reliable diagnostic procedure to determine surgical indications in primary aldosteronism. Because guidelines recommend multidetector computed tomography (CT) to evaluate the adrenal gland, some past reports used multidetector CT as a guide for adrenal venous sampling. However, the detailed anatomy of the right adrenal vein and its relationship with an accessory hepatic vein remains uncertain. The purpose of this study was to describe detailed anatomical variations of the right adrenal vein and to determine the concordance between CT and catheter venography in patients with primary aldosteronism. In total, 440 consecutive patients who underwent adrenal venous sampling were included. Four-phase dynamic CT was performed. Anatomical locations and variations of the right adrenal vein and its relationship with the accessory hepatic vein were compared with catheter venographic findings. Successful catheterization was achieved in 437 patients (99%). The right adrenal vein was visualized in the late arterial phase with CT in 420 patients (95%). The right adrenal vein formed a common trunk with the accessory hepatic vein in 87 patients (20%). CT identified the correct craniocaudal level of the orifice in 354 patients (84%). Anatomical variations, location, and angle of inflow of the right adrenal vein based on CT demonstrated high concordance with catheter venography. CT may provide useful information for preparation before adrenal venous sampling.
Comparison of adrenal vein sampling and computed tomography in the differentiation of primary aldosteronism.
Magill S B,Raff H,Shaker J L,Brickner R C,Knechtges T E,Kehoe M E,Findling J W
The Journal of clinical endocrinology and metabolism
Determination of the etiology of primary aldosteronism remains a diagnostic challenge. The most common types of primary aldosteronism are bilateral adrenal hyperplasia (BAH), aldosterone-producing adenomas (APA), and primary adrenal hyperplasia. Computed tomography (CT) and adrenal vein sampling (AVS) are the primary modalities used to differentiate these subtypes. The purpose of this study was to compare AVS and CT imaging of the adrenal glands in patients with hyperaldosteronism in whom CT imaging was normal or in whom focal unilateral or bilateral adrenal abnormalities were detected. The diagnosis of primary aldosteronism was made in 62 patients based on an elevated plasma aldosterone to PRA ratio and an elevated urinary aldosterone excretion rate. Thirty-eight patients had CT imaging and successful bilateral adrenal vein sampling and were included in the final analysis. AVS was considered the gold standard in determining the specific subtype of primary aldosteronism. There were 15 patients with APA, 21 patients with BAH, and 2 patients with primary adrenal hyperplasia. Plasma aldosterone was significantly higher in patients with APA (46.3 +/- 8.5 ng/dL; 1284 +/- 235 pmol/L) than in those with BAH (29.3 +/- 2.4 ng/dL; 813 +/- 11 pmol/L; P < 0.05). Plasma potassium was significantly lower in patients with APA (3.1 +/- 0.1 mmol/L) than in patients with BAH (3.5 +/- 0.1 mmol/L; P < 0.02). There was considerable overlap in the other biochemical indices (e.g. PRA and urinary aldosterone) in patients with the different subtypes. In patients with APA proven by AVS, eight had concordant findings with CT imaging, four had discordant findings, and three had normal CT imaging. In patients with BAH proven by AVS, four had concordant findings with CT imaging, eight had discordant findings, and nine had normal CT imaging. Compared with AVS, CT imaging was either inaccurate or provided no additional information in 68% of the patients with primary aldosteronism. We conclude that adrenal CT imaging is not a reliable method to differentiate primary aldosteronism. Adrenal vein sampling is essential to establish the correct diagnosis of primary aldosteronism.
Roles of clinical criteria, computed tomography scan, and adrenal vein sampling in differential diagnosis of primary aldosteronism subtypes.
Mulatero Paolo,Bertello Chiara,Rossato Denis,Mengozzi Giulio,Milan Alberto,Garrone Corrado,Giraudo Giuseppe,Passarino Giorgio,Garabello Domenica,Verhovez Andrea,Rabbia Franco,Veglio Franco
The Journal of clinical endocrinology and metabolism
CONTEXT:In patients with primary aldosteronism (PA), it is fundamental to distinguish between subtypes that benefit from different therapies. Computed tomography (CT) scans lack sensitivity and specificity and must be followed by adrenal venous sampling (AVS). Because AVS is not widely available, a list of clinical criteria that indicate the presence of an aldosterone-producing adenoma (APA) has been suggested. OBJECTIVE AND DESIGN:The objective of the study was to test the sensitivity and specificity of the last generation CT scans, test prospectively the usefulness of clinical criteria in the diagnosis of APA, and develop a flow chart to be used when AVS is not easily available. SETTING:Hypertensive patients referred to our hypertension unit were included in our study. PATIENTS:Seventy-one patients with confirmed PA participated in our study. INTERVENTION:All patients had a CT scan and underwent AVS. MAIN OUTCOME MEASURE:Final diagnosis of APA was the main measure. RESULTS:A total of 44 and 56% of patients were diagnosed as having an APA and a bilateral adrenal hyperplasia (BAH), respectively. Twenty percent of patients with PA displayed hypokalemia. CT scans displayed a sensitivity of 0.87 and a specificity of 0.71. The posture test displayed a lower sensitivity and specificity (0.64 and 0.70, respectively). The distribution grades of hypertension were not significantly different between APA and BAH. Biochemical criteria of high probability of APA displayed a sensitivity of 0.32 and a specificity of 0.95. CONCLUSIONS:This study underlines the central role of AVS in the subtype diagnosis of PA. The use of the clinical criteria to distinguish between APA and BAH did not display a satisfactory diagnostic power.
Diagnostic accuracy of adrenal venous sampling in comparison with other parameters in primary aldosteronism.
Minami Isao,Yoshimoto Takanobu,Hirono Yuki,Izumiyama Hajime,Doi Masaru,Hirata Yukio
This retrospective study was aimed 1) to compare the difference of the findings between adrenal CT scan and adrenal venous sampling (AVS) in 35 cases with definite primary aldosteronism (PA) for assessment of the diagnostic efficacy of PA subgroup (unilateral and bilateral adrenal hypersecretion: UAH and BAH), and 2) to determine the clinical and biochemical parameters as potential predictors for PA subgroup. There were significant discordant results based on AVS and CT scan in subgrouping PA; 9 of 17 BAH patients (53%) had unilateral lesion on CT scan, while 4 of 18 UAH patients (22%) had no apparent or bilateral lesions on CT scan. Among three diagnostic criteria, absolute values of plasma aldosterone concentration (PAC) in both adrenal veins, lateralized and contralateral ratios of aldosterone/cortisol after ACTH stimulation during AVS to determine the laterality, none of them showed 100% diagnostic accuracy if applied alone. Among several clinical and biochemical parameters, hypokalemia (<3.4 mEq/l), younger age (<52 y) and poor response of PAC (<1.45) after furosemide-upright posture, proved to be significant predictors for UAH, with higher specificities (100%, 88%, 94%, respectively). Therefore, despite AVS as a gold standard method to determine the laterality of aldosterone hypersecretion in PA, our study shows that no single criterion could provide definite diagnostic value for its laterality by AVS. It is also suggested that most PA patients, if not all, with a distinct unilateral adrenal lesion on CT accompanied by hypokalemia, younger age and poor aldosterone response to renin stimulation, could undergo adrenalectomy without prior AVS.
A clinical prediction score to diagnose unilateral primary aldosteronism.
Küpers Elselien M,Amar Laurence,Raynaud Alain,Plouin Pierre-François,Steichen Olivier
The Journal of clinical endocrinology and metabolism
CONTEXT:Adrenal venous sampling is recommended to assess whether aldosterone hypersecretion is lateralized in patients with primary aldosteronism. However, this procedure is invasive, poorly standardized, and not widely available. OBJECTIVE:Our goal was to identify patients' characteristics that can predict unilateral aldosterone hypersecretion in some patients who could hence bypass adrenal venous sampling before surgery. DESIGN AND SETTING:A cross-sectional diagnostic study was performed from February 2009 to July 2010 at a single center specialized in hypertension care. PATIENTS:A total of 101 consecutive patients with primary aldosteronism who underwent adrenal venous sampling participated in the study. The autonomy of aldosterone hypersecretion was assessed with the saline infusion test. INTERVENTION:Adrenal venous sampling was performed without ACTH infusion but with simultaneous bilateral sampling. MAIN OUTCOME MEASURES:Variables independently associated with a lateralized adrenal venous sampling in multivariate logistic regression were used to derive a clinical prediction rule. RESULTS:Adrenal venous sampling was successful in 87 patients and lateralized in 49. All 26 patients with a typical Conn's adenoma plus serum potassium of less than 3.5 mmol/liter or estimated glomerular filtration rate of at least 100 ml/min/1.73 m2 (or both) had unilateral primary aldosteronism; this rule had 100% specificity (95% confidence interval, 91-100) and 53% sensitivity (95% confidence interval, 38-68). CONCLUSIONS:If our results are validated on an independent sample, adrenal venous sampling could be omitted before surgery in patients with a typical Conn's adenoma if they meet at least one of two supplementary biochemical characteristics (serum potassium<3.5 mmol/liter or estimated glomerular filtration rate ≥100 ml/min/1.73 m2).
Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism.
Kempers Marlies J E,Lenders Jacques W M,van Outheusden Lieke,van der Wilt Gert Jan,Schultze Kool Leo J,Hermus Ad R M M,Deinum Jaap
Annals of internal medicine
BACKGROUND:Computed tomography (CT), magnetic resonance imaging (MRI), and adrenal vein sampling (AVS) are used to distinguish unilateral from bilateral increased aldosterone secretion as a cause of primary aldosteronism. This distinction is crucial because unilateral primary aldosteronism can be treated surgically, whereas bilateral primary aldosteronism should be treated medically. PURPOSE:To determine the proportion of patients with primary aldosteronism whose CT or MRI results with regard to unilateral or bilateral adrenal abnormality agreed or did not agree with those of AVS. DATA SOURCES:PubMed, MEDLINE, EMBASE, and Cochrane Library, 1977 to April 2009. STUDY SELECTION:Studies describing adults with primary aldosteronism who underwent CT/MRI and AVS were included. Of 472 initially identified studies, 38 met the selection criteria; extractable data were available for 950 patients. DATA EXTRACTION:The CT/MRI result was considered accurate when AVS showed unilaterally increased aldosterone secretion on the same side as the abnormality seen on CT/MRI or when AVS showed symmetric aldosterone secretion and CT/MRI revealed bilateral or no unilateral abnormality. DATA SYNTHESIS:In 37.8% of patients (359 of 950), CT/MRI results did not agree with AVS results. If only CT/MRI results had been used to determine lateralization of an adrenal abnormality, inappropriate adrenalectomy would have occurred in 14.6% of patients (where AVS showed a bilateral problem), inappropriate exclusion from adrenalectomy would have occurred in 19.1% (where AVS showed unilateral secretion), and adrenalectomy on the wrong side would have occurred in 3.9% (where AVS showed aldosterone secretion on the opposite side). LIMITATION:The lack of follow-up data in the included articles made it impossible to confirm that adrenalectomies were performed appropriately. CONCLUSION:When AVS is used as the criterion standard test for diagnosing laterality of aldosterone secretion in patients with primary aldosteronism, CT/MRI misdiagnosed the cause of primary aldosteronism in 37.8% of patients. Relying only on CT/MRI may lead to inappropriate treatment of patients with primary aldosteronism.
Subtype prediction of primary aldosteronism by combining aldosterone concentrations in the left adrenal vein and inferior vena cava: a multicenter collaborative study on adrenal venous sampling.
Fujii Yuichi,Umakoshi Hironobu,Wada Norio,Ichijo Takamasa,Kamemura Kohei,Matsuda Yuichi,Kai Tatsuya,Fukuoka Tomikazu,Sakamoto Ryuichi,Ogo Atsushi,Suzuki Tomoko,Nanba Kazutaka,Tsuiki Mika,Naruse Mitsuhide,
Journal of human hypertension
Subtype diagnosis of primary aldosteronism (PA) by adrenal vein sampling (AVS) is recommended as a mandatory step for indicating adrenal surgery. It is a technically demanding procedure, especially in the right adrenal vein. The aim of the study was to predict the subtype diagnosis in the absence of values from the right AVS. From the databases of nine centers (WAVES-J), 308 patients with PA who underwent successful AVS were studied. Based on the ipsilateral ratio (IR) (aldosterone/cortisol ratio of the left adrenal vein [A/C] / aldosterone/cortisol ratio of the inferior vena cava [A/C]), the patients were divided into two groups: the patients with IR ≥ 1.0 (n = 262) and those with IR < 1.0 (n = 46). In patients with IR > 1.0, the A/C was significantly higher in patients with the left unilateral subtype than in patients with the bilateral subtype. Receiver operating characteristic (ROC) curve analysis revealed that an A/C cutoff >68 showed 70.8% sensitivity and 93.5% specificity for the left unilateral subtype. On the other hand, in patients with IR < 1.0, the A/C was significantly lower in patients with the right unilateral subtype. ROC analysis revealed that an A/C cutoff <9 showed 86.7% sensitivity and 75.0% specificity for the right unilateral subtype. Hence, the combination of the IR and A/C ratio in the left adrenal vein is useful for predicting the subtype. The present results provide important information for patients with PA in whom AVS was unsuccessful in the right adrenal vein.
Comparison between adrenal venous sampling and computed tomography in the diagnosis of primary aldosteronism and in the guidance of adrenalectomy.
Zhu Limin,Zhang Ying,Zhang Hua,Zhou Wenlong,Shen Zhoujun,Zheng Fangfang,Tang Xiaofeng,Tao Bo,Zhang Jin,Lu Xiaohong,Xu Jianzhong,Chu Shaoli,Zhu Dingliang,Gao Pingjin,Wang Ji-Guang
In our series of patients with primary aldosteronism, we compared diagnostic concordance and clinical outcomes after adrenalectomy between adrenal venous sampling (AVS) and computed tomography (CT) imaging.Our retrospective analysis included 886 patients with primary aldosteronism diagnosed in our hospital between 2005 and 2014. Of them, 269 patients with CT unilateral adrenal disease were included in the analysis on the diagnostic concordance and 126 patients with follow-up data in the analysis on clinical outcomes after adrenalectomy. Hypertension was considered cured if systolic/diastolic blood pressure (BP) was controlled (<140/90 mm Hg) without medication and improved if BP was controlled with a reduced number of antihypertensive drugs.In 269 patients with CT unilateral adrenal disease, the overall concordance rate between AVS and CT was 50.5% for lateralization on the same side. The concordance rate decreased with increasing age, with highest rate of 61% in patients aged <30 years (n = 16). In 126 patients with follow-up data after adrenalectomy, the AVS- (n = 96) and CT-guided patients (n = 30) had similar characteristics before adrenalectomy. After andrenalectomy, the AVS-guided patients had a significantly higher serum potassium concentration (4.3 ± 0.3 vs 4.0 ± 0.5 mmol/L, P = 0.04) and rate of cured and improved hypertension (98% vs 87%, P = 0.03). The AVS-guided patients (n = 50) had slightly higher cured rate than the CT-guided patients (n = 11) in those older than 50 years (26.0% vs 18.2%, P = 0.72). The age below which the cured rate in the CT-guided patients was 100% was 30 years.AVS guidance had moderate concordance with CT and slightly improved clinical outcomes after adrenalectomy. The age below which CT unilateralization achieved 100% cured rate was approximately 30 years.
Comprehensive Analysis of Steroid Biomarkers for Guiding Primary Aldosteronism Subtyping.
Turcu Adina F,Wannachalee Taweesak,Tsodikov Alexander,Nanba Aya T,Ren Jianwei,Shields James J,O'Day Patrick J,Giacherio Donald,Rainey William E,Auchus Richard J
Hypertension (Dallas, Tex. : 1979)
Adrenal vein sampling (AVS) is required to distinguish unilateral from bilateral aldosterone sources in primary aldosteronism (PA), and cortisol is used for AVS data interpretation, but cortisol has several pitfalls. In this study, we present the utility of several other steroids in PA subtyping, both during AVS, as well as in peripheral serum. We included patients with PA who underwent AVS at University of Michigan between 2012 and 2018. We used mass spectrometry to simultaneously quantify 17 steroids in adrenal veins (AV) and periphery, both at baseline and after cosyntropin administration. PA was classified as unilateral or bilateral based on a lateralization index ≥ or <4, respectively, separately for baseline and post-cosyntropin administration. Of 131 participants, AV catheterizations was deemed failed in 28 (21 %) patients (36 AVs) at baseline. Eight steroids demonstrated higher AV/periphery ratios than cortisol (<0.01 for all); 11β-hydroxyandrostenedione, 11-deoxycortisol, and corticosterone rescued most failed baseline catheterizations. Lateralization was generally consistent when using these alternative steroids. Based on pre- and post-cosyntropin data, the remaining 103 patients were classified as: U/U, 37; B/B, 32; U/B, 20; B/U, 14. Discriminant analysis of multi-steroid panels from peripheral serum showed distinct profiles across the 4 groups, with highest aldosterone, 18-oxocortisol and 11-deoxycorticosterone in U/U patients. In conclusion, 11β-hydroxyandrostenedione and 11-deoxycortisol are superior to cortisol for AVS data interpretation. Single assay multi-steroid panels measured in peripheral serum are helpful in stratified PA subtyping and have the potential to circumvent AVS in a subset of patients with PA.
Subtyping of primary aldosteronism with adrenal vein sampling: Hormone- and side-specific effects of cosyntropin and metoclopramide.
Rossitto Giacomo,Maiolino Giuseppe,Lenzini Livia,Bisogni Valeria,Seccia Teresa Maria,Cesari Maurizio,Iacobone Maurizio,Rossi Gian Paolo
BACKGROUND:Cosyntropin and metoclopramide can affect the subtyping of primary aldosteronism when used with adrenal vein sampling by exerting hormone- and side-specific effects on cortisol and aldosterone secretion. We investigated how these stimuli affect the selectivity index, the relative aldosterone secretion index, and the lateralization index in consecutive primary aldosteronism patients submitted to adrenal vein sampling. METHODS:We recruited 171 patients; of these, 149 underwent adrenal vein sampling before and after stimulation with cosyntropin (250 µg intravenous bolus, n= 53, 73% with an aldosterone-producing adenoma) or with metoclopramide (10 mg intravenous bolus, n= 96, 65% aldosterone-producing adenoma), and 32 with an aldosterone-producing adenoma were investigated for the relative gene expression of dopamine, melanocortin 2, and 5-hydroxytryptamine (serotonin) 4 receptor with microarrays. Cosyntropin increased the selectivity index similarly on both sides; metoclopramide did not. Cosyntropin decreased relative aldosterone secretion index on the aldosterone-producing adenoma side but not contralaterally. Metoclopramide did not affect the selectivity index, but increased the relative aldosterone secretion index similarly on both sides. Because of these changes, cosyntropin decreased the lateralization index, while metoclopramide did not affect it. The relative gene expression of melanocortin 2, albeit heterogeneous across tumors, was 35% less (P<.0001) in aldosterone-producing adenoma than in the normal adrenal cortex, while dopamine receptor D2 and 5-hydroxytryptamine (serotonin) 4 receptors did not differ between tissues. CONCLUSION:Cosyntropin, while facilitating ascertainment of selectivity, lessens the lateralization, likely because of a blunted melanocortin 2 expression in aldosterone-producing adenoma. The similar expression of dopamine and 5-hydroxytryptamine (serotonin) 4 receptors in aldosterone-producing adenoma and the normal adrenal cortex can explain why metoclopramide increased the relative aldosterone secretion index on both sides and, therefore, failed to increase the lateralization index.
Discordance between imaging and immunohistochemistry in unilateral primary aldosteronism.
Nanba Aya T,Nanba Kazutaka,Byrd James B,Shields James J,Giordano Thomas J,Miller Barbara S,Rainey William E,Auchus Richard J,Turcu Adina F
OBJECTIVE:Correct subtyping of primary aldosteronism (PA) is essential for good surgical outcomes. Adrenal vein sampling (AVS) and/or computed tomography (CT) are used for PA subclassification. Clinical and/or biochemical improvement after surgery, however, is not always achieved in patients with presumed unilateral PA. We aimed to identify the pitfalls in PA subclassification leading to surgical treatment failures. PATIENTS AND DESIGN:We retrospectively studied 208 patients who underwent adrenal vein sampling (AVS) for PA subclassification in a tertiary referral centre, between January 2009 and August 2016. Simultaneous bilateral AVS was performed before and after cosyntropin administration. We implemented immunohistochemistry for aldosterone synthase (CYP11B2) and 17α-hydroxylase/17,20 lyase (CYP17A1) in adrenal glands resected from patients without improvement of PA after surgical treatment and from those with limitations in AVS interpretation. RESULTS:Of 55 patients who underwent adrenalectomy, three (5.5%) had no improvement of PA. All three patients underwent partial adrenalectomy to remove a CT-detected nodule present on the same side with AVS lateralization. Immunohistochemistry revealed a CYP11B2-negative nodule in both cases available. All patients who underwent total adrenalectomy based on AVS lateralization benefitted from surgery, including three patients with unilateral unsuccessful AVS and aldosterone suppression in the catheterized side vs inferior vena cava. CONCLUSIONS:Radiographically identified adrenal nodules are not always a source of PA, even when ipsilateral with AVS lateralization. These data caution against reliance on imaging findings, either alone or in conjunction with AVS, to guide surgery for PA.
Sex Differences in Renal Outcomes After Medical Treatment for Bilateral Primary Aldosteronism.
Nakamaru Ryo,Yamamoto Koichi,Akasaka Hiroshi,Rakugi Hiromi,Kurihara Isao,Yoneda Takashi,Ichijo Takamasa,Katabami Takuyuki,Tsuiki Mika,Wada Norio,Yamada Tetsuya,Kobayashi Hiroki,Tamura Kouichi,Ogawa Yoshihiro,Kawashima Junji,Inagaki Nobuya,Fujita Megumi,Oki Kenji,Kamemura Kohei,Tanabe Akiyo,Naruse Mitsuhide,
Hypertension (Dallas, Tex. : 1979)
A higher incidence of bilateral primary aldosteronism in women is reported. Treatment of bilateral primary aldosteronism usually involves mineralocorticoid receptor antagonists. However, the impact of sex on renal outcomes is unknown. We compared renal outcomes between the sexes after mineralocorticoid receptor antagonist initiation by analyzing data obtained from 415 female and 313 male patients with bilateral primary aldosteronism who were treated with spironolactone or eplerenone in the JPAS (Japan Primary Aldosteronism Study). Over the course of 5 years, the temporal reduction in the estimated glomerular filtration rate was greater in women than in men (<0.001). Systolic blood pressure levels were equal between the sexes, despite higher doses of antihypertensive drugs in men. The mean of the annual decline in estimated glomerular filtration rate during what we termed the late phase, or 6 to 60 months after mineralocorticoid receptor antagonist initiation, was larger in women than in men after adjusting for patient characteristics (-1.33 mL/min per 1.73 m per year versus -1.04 mL/min per 1.73 m per year, <0.01). Female sex was a significant predictor of greater annual decline during the late phase in patients taking spironolactone but not in those taking eplerenone. Spironolactone use and diabetes were independent predictors of a greater annual decline in estimated glomerular filtration rate during the late phase in women. These findings suggest that female sex is associated with poorer renal outcomes in patients receiving mineralocorticoid receptor antagonist for bilateral primary aldosteronism.
Can incomplete adrenal venous sampling data be used in predicting the subtype of primary aldosteronism?
Lin Lede,Zhou Liang,Guo Yiding,Liu Zhenghuan,Chen Tao,Liu Zhihong,Wang Kunjie,Li Jiaqi,Zhu Yuchun,Ren Yan
BACKGROUND:Adrenal venous sampling (AVS) is the gold standard for preoperative differentiation between unilateral and bilateral primary aldosteronism (PA). However, results are sometimes vitiated by failing to access the right adrenal vein. MATERIALS AND METHODS:The present study assumed that clinical decisions can be made with incomplete AVS data, by comparing aldosterone/cortisol (A/C) ratio in both left and right adrenal veins with that in the inferior vena cava (LAV/IVC and RAV/IVC). Receiver operation characteristic (ROC) curve and scatterplot were used to certify the upper and lower cutoffs and to analyze the significance of discrimination. One hundred and sixty patients diagnosed with PA from April 2017 to June 2018 underwent AVS in the Urology Department of West China Hospital, Chengdu, China. One hundred and eleven with complete AVS data were divided into 3 groups: left-sided (N=40), right-sided (N=29) and bilateral (N=42). We also collected patients from September 2018 to April 2019 in our department as validation cohort to test our hypothesis. RESULTS:On the basis of LAV/IVC, RAV/IVC and diagnostic category, upper cutoff was 1.14 (50% sensitivity and 100% specificity) and lower cutoff 0.07 (27.5% sensitivity and 100% specificity) for LAV/IVC, and 1.04 (55% sensitivity and 100% specificity) and 0.08 (40% sensitivity and 100% specificity), respectively, for RAV/IVC. CONCLUSION:The diagnostic model in this study contributes to clinical decision-making in patients with only partial PA with incomplete AVS data.
Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism.
Ladurner Roland,Sommerey Sandra,Buechner Stefan,Dietz Anna,Degenhart Christoph,Hallfeldt Klaus,Gallwas Julia
European journal of clinical investigation
INTRODUCTION:The correct differentiation between unilateral and bilateral adrenal involvement in patients with primary aldosteronism (PA) is of utmost importance to justify surgical treatment. The aim of this study was to determine the accuracy of adrenal imaging compared to adrenal venous sampling (AVS), histopathology and postoperative outcome. METHODS:The data of all patients with unequivocal AVS who underwent unilateral laparoscopic adrenalectomy for primary aldosteronism between May 2004 and April 2015 were entered in this retrospective study. We compared computed tomography (CT) and magnetic resonance imaging (MRI) results with corresponding AVS data, histopathology findings and postoperative outcome. RESULTS:A total of 175 patients underwent unilateral laparoscopic adrenalectomy for primary aldosteronism. AVS was successful in 152 patients and postoperative outcome available in 148 patients. Despite unilateral disease according to AVS results, bilateral normal glands were seen in 15 MRI (17·2%) and 7 CT scans (8·5%), respectively. Unilateral enlargement of the nonhypersecreting adrenal gland was found in three MRI (3·5%) and 10 CT scans (12·2%) of patients who showed aldosterone hypersecretion deriving from the contralateral gland. Fifteen MRI (17·2%) and 18 CT scans (22·0%) revealed bilateral adrenal pathology despite unilateral aldosterone hypersecretion. CONCLUSION:The accuracy of CT and magnetic resonance imaging in predicting unilateral disease is poor. AVS appears to be an essential diagnostic step to identify those patients who may benefit from unilateral adrenalectomy.
Prevalence, Subtype Classification, and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China.
Xu Fen,Gao Zhangwei,Wang Guoqiang,Gao Yang,Guo Yang,Guo Yutong,Zhou Zhou
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:To investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA. METHODS:A prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018. RESULTS:Of the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients' blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups. CONCLUSION:It is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.
Bilateral aldosterone suppression and its resolution in adrenal vein sampling of patients with primary aldosteronism: analysis of data from the WAVES-J study.
Shibayama Yui,Wada Norio,Umakoshi Hironobu,Ichijo Takamasa,Fujii Yuichi,Kamemura Kohei,Kai Tatsuya,Sakamoto Ryuichi,Ogo Atsushi,Matsuda Yuichi,Fukuoka Tomikazu,Tsuiki Mika,Suzuki Tomoko,Naruse Mitsuhide
CONTEXT:In adrenal vein sampling (AVS) for patients with primary aldosteronism, the contralateral ratio of aldosterone/cortisol (A/C) between the nondominant adrenal vein and the inferior vena cava is one of the best criteria for determining lateralized aldosterone secretion. Despite successful cannulation in some patients, the A/C ratios in the adrenal veins are bilaterally lower than that in the inferior vena cava (bilateral aldosterone suppression; BAS). OBJECTIVES:To investigate the prevalence of BAS in AVS and how to resolve this condition. DESIGN AND SETTING:Retrospective study involving nine referral centres. PATIENTS:Four hundred and ninety-one patients who were confirmed as having primary aldosteronism and had an AVS between January 2006 and December 2013. MEASUREMENTS:The prevalence of BAS before and after ACTH stimulation was compared. In addition, we investigated other methods for overcoming BAS. RESULTS:In 304 patients with successful AVS before ACTH stimulation, BAS was observed in 29 (9·5%). BAS was resolved after ACTH stimulation in 22 patients. In 276 patients with successful AVS both before and after ACTH stimulation, the frequency of BAS was significantly reduced after ACTH (8·7% vs 2·5%, P < 0·01). In a few patients, BAS was also resolved by adding a sampling point at the common trunk of the left adrenal vein and by an alternative drainage vein from the adrenal tumour. CONCLUSIONS:BAS sometimes occurs in AVS without ACTH stimulation. ACTH stimulation significantly reduces BAS with a single AVS procedure.
Nomogram-Based Preoperative Score for Predicting Clinical Outcome in Unilateral Primary Aldosteronism.
Yang Yi,Williams Tracy Ann,Song Ying,Yang Shumin,He Wenwen,Wang Kanran,Cheng Qingfeng,Ma Linqiang,Luo Ting,Yang Jun,Reincke Martin,Burrello Jacopo,Li Qifu,Mulatero Paolo,Hu Jinbo
The Journal of clinical endocrinology and metabolism
CONTEXT:More than half of patients diagnosed with unilateral primary aldosteronism (UPA) suffer from persisting hypertension after unilateral adrenalectomy. OBJECTIVE:The objective of this work is to develop and validate a nomogram-based preoperative score (NBPS) to predict clinical outcomes after unilateral adrenalectomy for UPA. DESIGN AND SETTING:The NBPS was developed in an Asian cohort by incorporating predictors independently associated with remission of hypertension after unilateral adrenalectomy for UPA and validated in a Caucasian cohort. PARTICIPANTS:Participants comprised patients with UPA achieving complete biochemical success after unilateral adrenalectomy. MAIN OUTCOME MEASURE:Measurements included the predictive performance of the NBPS compared with 2 previously developed outcome prediction scores: aldosteronoma resolution score (ARS) and primary aldosteronism surgical outcome (PASO) score. RESULTS:Ninety-seven of 150 (64.7%) patients achieved complete clinical success after unilateral adrenalectomy in the training cohort and 57 out of 165 (34.5%) in the validation cohort. A nomogram was established incorporating sex, duration of hypertension, aldosterone-to-renin ratio, and target organ damage. The nomogram showed good C indices and calibration curves both in Asian and Caucasian cohorts. The area under the receiver operating characteristic curve (AUC) of the NBPS for predicting hypertension remission in the training cohort was 0.853 (0.786-0.905), which was superior to the ARS (0.745 [0.667-0.812], P = .019) and PASO score (0.747 [0.670-0.815], P = .012). The AUC of the NBPS in the validation cohort was 0.830 (0.764-0.884), which was higher than the ARS (0.745 [95% CI, 0.672-0.810], P = .045), but not significantly different from the PASO score (0.825 [95% CI, 0.758-0.880], P = .911). CONCLUSION:The NBPS is useful in predicting clinical outcome for UPA patients, especially in the Asian population.
[Performance Verification of Plasma Renin and Aldosterone Examination with Chemiluminescence Immunoassay and Its Screening Efficacy for Primary Aldosteronism].
Liu Zhi,Zhang Mei,Ren Yan,Chen Tao,Gao Hong-Jiao,He He,Ayiligui ,Liu Ying,An Zhen-Mei
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition
Objective:To evaluate the performance of chemiluminescence immunoassay (CLIA) in examining renin and aldosterone and to determine its value for screening for primary aldosteronism (PA). Methods:According to the relevant documents of Clinical and Laboratory Standards Institute (CLSI), we verified the precision, linear range and carryover rate of examining renin and aldosterone with CLIA. The study included 91 suspected PA patients, using two methods, CLIA and radioimmunoassay (RIA), to examine renin and aldosterone levels in order to compare the correlation between the two methods and their value for PA screening. Results:The precision, linear range and carryover rate of examining renin and aldosterone with CLIA met the requirements. In patients with suspected PA, the correlation coefficients of renin, aldosterone and aldosterone-to-renin ratio (ARR) assessed by CLIA and RIA were 0.901, 0.861 and 0.847 respectively (all <0.001). When the patients were in the upright position and the ARR was 5.636 (ng/dL)/(ng/L), the CLIA method had 79.1% sensitivity and 93.7% specificity for PA screening; when ARR was 14.084 (ng·dL )/(ng·[mL·h] ), the RIA method had 93.0% sensitivity and 83.3% specificity for PA screening. When the patients were in the supine position, and the ARR was 5.640 (ng/dL)/(ng/L), the CLIA method had 97.7% sensitivity and 81.2% specificity for PA screening; when ARR was 33.494 (ng·dL )/(ng·[mL·h] ), RIA had 95.3% sensitivity and 70.8% specificity for PA screening . Conclusion:The performance of the CLIA kit in assessing the concentration of renin and aldosterone meets the clinical requirements. Regarding preliminary PA screening, upright-position ARR had higher specificity, but lower sensitivity compared with supine-position ARR.
Diagnostic accuracy of aldosterone and renin measurement by chemiluminescent immunoassay and radioimmunoassay in primary aldosteronism.
Burrello Jacopo,Monticone Silvia,Buffolo Fabrizio,Lucchiari Manuela,Tetti Martina,Rabbia Franco,Mengozzi Giulio,Williams Tracy A,Veglio Franco,Mulatero Paolo
Journal of hypertension
OBJECTIVE:Up to 50% of hypertensive patients should be screened for primary aldosteronism, using the aldosterone to renin (or plasma renin activity) ratio [aldosterone to active renin ratio (AARR) and aldosterone to plasma renin activity ratio (ARR), respectively]. Aim of the study was to prospectively compare the diagnostic accuracy of AARR (measured by chemiluminescent immunoassay) and ARR (measured by radioimmunoassay) as screening tests for primary aldosteronism and aldosterone assays (measured by chemiluminescence and radioimmunoassay) during confirmatory testing. METHODS:One hundred patients were screened for primary aldosteronism and 34 underwent confirmatory testing. The cut-offs for ARR and AARR were 30 ng/dl/ng/ml/h and 3.7 ng/dl/mU/l, respectively. Patients with positive confirmatory test underwent subtype diagnosis. RESULTS:Seventy-five patients were essential hypertensive patients, 15 had idiopathic hyperaldosteronism, five aldosterone-producing adenoma (APA) and five with undefined diagnosis. The AARR displayed a sensitivity of 90% and a specificity of 99%, the ARR had a sensitivity of 100% and a specificity of 73%. Of the two of 20 primary aldosteronism patients missed by AARR, none resulted affected by APA. All primary aldosteronism patients were correctly diagnosed by chemiluminescence at confirmatory testing. In the total sample of 168 measurements both the correlation for plasma renin activity with renin and for aldosterone in chemiluminescence and radioimmunoassay were highly significant (ρ = 0.70, P < 0.001 and ρ = 0.78, P < 0.001, respectively). On receiver operator characteristics curves, the area under the curve for AARR was 0.989 [95% confidence interval (CI) 0.97-1] and 0.934 for ARR (95% CI 0.89-0.98), which were not significantly different. CONCLUSION:The automated aldosterone and renin chemiluminescent assay is a reliable alternative to the radioimmunometric method, especially for APA detection.
Confirmatory Tests for the Diagnosis of Primary Aldosteronism: A Prospective Diagnostic Accuracy Study.
Song Ying,Yang Shumin,He Wenwen,Hu Jinbo,Cheng Qingfeng,Wang Yue,Luo Ting,Ma Linqiang,Zhen Qianna,Zhang Suhua,Mei Mei,Wang Zhihong,Qing Hua,Bruemmer Dennis,Peng Bin,Li Qifu,
Hypertension (Dallas, Tex. : 1979)
The diagnosis of primary aldosteronism typically requires at least one confirmatory test. The fludrocortisone suppression test is generally accepted as a reliable confirmatory test, but it is cumbersome. Evidence from accuracy studies of the saline infusion test (SIT) and the captopril challenge test (CCT) has provided conflicting results. This prospective study aimed to evaluate the diagnostic accuracy of the SIT and CCT using fludrocortisone suppression test as the reference standard. One hundred thirty-five patients diagnosed with primary aldosteronism and 101 patients diagnosed with essential hypertension who completed the 3 confirmatory tests were included for the diagnostic accuracy analysis. The areas under the receiver-operator characteristics curves of the CCT and SIT were 0.96 (95% confidence interval [CI], 0.92-0.98) and 0.96 (95% CI, 0.92-0.98), respectively, using post-test plasma aldosterone concentration (PAC) for diagnosis. However, the areas under the receiver-operator characteristics curves of the CCT decreased to 0.71 (95% CI, 0.65-0.77) when the PAC suppression percentage was used to diagnose primary aldosteronism. The optimal cutoff of PAC post-CCT was set at 11 ng/dL, resulting in a sensitivity of 0.90 (95% CI, 0.84-0.95) and a specificity of 0.90 (95% CI, 0.83-0.95), which were not significantly different from those of SIT (with PAC post-SIT set at 8 ng/dL, sensitivity: 0.85 [95% CI, 0.78-0.91], =0.192; specificity: 0.92 [95% CI, 0.85-0.97], =0.551). In conclusion, both CCT and SIT are accurate alternatives to the more complex fludrocortisone suppression test. Because CCT is safe and much easier to perform, it may serve as a more feasible alternative. When interpreting the results of CCT, PAC post-CCT is highly recommended.
Unilateral Disease Is Common in Patients With Primary Aldosteronism Without Adrenal Nodules.
Sam Davis,Kline Gregory A,So Benny,Przybojewski Stefan J,Leung Alexander A
The Canadian journal of cardiology
BACKGROUND:Patients with primary aldosteronism (PA) without apparent adrenal nodularity have not been well characterised in the literature. The aim of this study was to assess for unilateral aldosterone hypersecretion among patients with primary aldosteronism with normal-appearing adrenals using adrenal vein sampling (AVS). METHODS:In this cross-sectional study performed at a Canadian tertiary care centre, we reviewed all consecutive PA patients lacking a definitive adrenal nodule who were referred for AVS in the work-up of PA between January 2006 and May 2018. AVS indications included an elevated aldosterone-to-renin ratio and high-probability features of PA. RESULTS:In total, 174 patients were included (mean age, 52.0 years; 62.6% male), and 70 (40.2%) had unilateral aldosterone hypersecretion. There was a positive linear association between higher age categories (by decade) and lateralisation (P = 0.03). For every decade of age, there was a 30% higher odds of lateralisation (odds ratio, 1.03 per year; 95% confidence interval, 1.00-1.05). The frequency of lateralisation was higher in males compared with females (47.7% vs 27.7%), with a 2-fold greater odds of unilateral disease (odds ratio, 2.38; 95% confidence interval, 1.23-4.61). Traditional biomarkers of lateralisation among patients with adrenal nodules (eg, serum potassium and aldosterone-to-renin ratio levels) were not predictive of lateralisation in this population. CONCLUSIONS:Many patients with PA who lack definitive adrenal nodules have lateralising disease. Efforts to optimise referrals for AVS may be prioritised by focusing on patients most likely to have unilateral disease, especially males and older adults.
Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism.
Williams Tracy A,Burrello Jacopo,Sechi Leonardo A,Fardella Carlos E,Matrozova Joanna,Adolf Christian,Baudrand René,Bernardi Stella,Beuschlein Felix,Catena Cristiana,Doumas Michalis,Fallo Francesco,Giacchetti Gilberta,Heinrich Daniel A,Saint-Hilary Gaëlle,Jansen Pieter M,Januszewicz Andrzej,Kocjan Tomaz,Nishikawa Tetsuo,Quinkler Marcus,Satoh Fumitoshi,Umakoshi Hironobu,Widimský Jiří,Hahner Stefanie,Douma Stella,Stowasser Michael,Mulatero Paolo,Reincke Martin
Hypertension (Dallas, Tex. : 1979)
Unilateral primary aldosteronism is the most common surgically correctable form of endocrine hypertension and is usually differentiated from bilateral forms by adrenal venous sampling (AVS) or computed tomography (CT). Our objective was to compare clinical and biochemical postsurgical outcomes of patients with unilateral primary aldosteronism diagnosed by CT or AVS and identify predictors of surgical outcomes. Patient data were obtained from 18 internationally distributed centers and retrospectively analyzed for clinical and biochemical outcomes of adrenalectomy of patients with surgical management based on CT (n=235 patients, diagnosed from 1994-2016) or AVS (526 patients, diagnosed from 1994-2015) using the standardized PASO (Primary Aldosteronism Surgical Outcome) criteria. Biochemical outcomes were highly different according to surgical management approach with a smaller proportion in the CT group achieving complete biochemical success (188 of 235 [80%] patients versus 491 of 526 [93%], P<0.001) and a greater proportion with absent biochemical success (29 of 235 [12%] versus 10 of 526 [2%], P<0.001). A diagnosis by CT was associated with a decreased likelihood of complete biochemical success compared with AVS (odds ratio, 0.28; 0.16-0.50; P<0.001). Clinical outcomes were not significantly different, but the absence of a postsurgical elevated aldosterone-to-renin ratio was a strong marker of complete clinical success (odds ratio, 14.81; 1.76-124.53; P=0.013) in the CT but not in the AVS group. In conclusion, patients diagnosed by CT have a decreased likelihood of achieving complete biochemical success compared with a diagnosis by AVS.
Construction of a predictive scoring system as a guide to screening and confirmation of the diagnosis of primary aldosteronism.
Kietsiriroje Noppadol,Wonghirundecha Rawipas,Suntornlohanakul Onnicha,Murray Robert D
BACKGROUND:Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. In Southern Thailand, the aldosterone-renin ratio (ARR) is only available within a small number of tertiary centres, necessitating need for a simple clinical assessment to determine the requirement for ARR. OBJECTIVE:This study aimed to identify predictive factors for the diagnosis of PA and generate a predictive scoring system (PSS) for use in screening and diagnosis of PA. PATIENTS AND METHODS:A total of 420 patients aged >15 years with paired plasma aldosterone concentration and plasma renin activity values allowing calculation of ARR were identified from the electronic hospital database between 2011 and 2016. RESULTS:The overall prevalence of PA was 16.7% (range; adrenal incidentaloma 5.6% to hypokalaemia 30%). Predictive factors for diagnosis of PA were as follows: age <60 years, BMI < 25 kg/m , presence of diabetes, ≥3 antihypertensive agents, serum sodium ≥ 141 mmol/L and serum potassium < 3.5 mmol/L. A predictive scoring system (PSS) (range -2 to 13) was generated by the coefficients of the variables with ROC curve AUC 0.87 [95% CI: 0.83-0.91]. Using the PSS, a total score <4 provided a robust negative predictive value (sensitivity, 0.97; specificity, 0.48; NPV, 0.99; PPV, 0.27) for PA. In patients at high risk of PA (PAC > 15 ng/dL and PRA < 1.0 ng/mL/hr), a PSS score > 9 had specificity and PPV of 100%, essentially confirming PA in these individuals. CONCLUSION:The proposed PSS for PA will enable more focused and cost-effective use of ARR screening and confirmatory testing. In our cohort, 40% and 42% of patients would not require ARR screening or confirmatory tests, respectively.
Influence of antihypertensive drugs in the subtype diagnosis of primary aldosteronism by adrenal venous sampling.
Nagasawa Motonori,Yamamoto Koichi,Rakugi Hiromi,Takeda Masao,Akasaka Hiroshi,Umakoshi Hironobu,Tsuiki Mika,Takeda Yoshiyu,Kurihara Isao,Itoh Hiroshi,Ichijo Takamasa,Katabami Takuyuki,Wada Norio,Shibayama Yui,Yoshimoto Takanobu,Ogawa Yoshihiro,Kawashima Junji,Sone Masakatsu,Inagaki Nobuya,Takahashi Katsutoshi,Fujita Megumi,Watanabe Minemori,Matsuda Yuichi,Kobayashi Hiroki,Shibata Hirotaka,Kamemura Kohei,Otsuki Michio,Fujii Yuichi,Ogo Atsushi,Okamura Shintaro,Miyauchi Shozo,Yanase Toshihiko,Suzuki Tomoko,Kawamura Takashi,Naruse Mitsuhide,
Journal of hypertension
OBJECTIVES:Because of the influence on the renin-angiotensin-aldosterone system, it is recommended to avoid, if possible, the use of angiotensin-converting-enzyme inhibitors, angiotensin II type 1 receptor blockers, diuretics, β-blockers, and mineralocorticoid receptor antagonists during the diagnostic period of primary aldosteronism. A laterality index more than 4 in adrenocorticotropic hormone (ACTH)-stimulated adrenal venous sampling (ACTH-AVS) is a widely used classification of the unilateral subtype that can benefit from adrenalectomy. Here, we revealed clinical features of patients taking drugs that could affect the primary aldosteronism diagnosis (DAPD) and investigated whether the classification with laterality index more than 4 in ACTH-AVS is applicable to these patients. PATIENTS AND METHODS:Using a large database of primary aldosteronism patients in Japan, we analyzed 2122 patients with successful ACTH-AVS. RESULTS:Patients who received any DAPD (n = 209) showed higher prevalence of comorbidity burdens and took more antihypertensive drugs compared with patients without DAPD. In patients taking DAPD, those with laterality index more than 4 had a higher prevalence of hypokalemia, a higher aldosterone-to-renin ratio and a higher prevalence of adrenal mass than those with laterality index of 4 or less. Adrenalectomy was performed in 76% patients with laterality index more than 4 and 20% with laterality index of 4 or less. Patients who underwent adrenalectomy showed biochemical cure in 89% with laterality index more than 4 and 50% with laterality index of 4 or less (P = 0.001). Multivariate regression analysis showed that laterality index more than 4 was an independent predictor of a biochemical cure. Biochemical cure rate in patients with laterality index more than 4 was consistently high, irrespective of the potential effect of individual DAPD on laterality index. CONCLUSION:Our findings suggest that in primary aldosteronism patients to whom DAPD were administrated due to severe clinical features, laterality index more than 4 in ACTH-AVS could accurately predict a biochemical cure after adrenalectomy.
A clinical prediction score for diagnosing unilateral primary aldosteronism may not be generalizable.
Venos Erik S,So Benny,Dias Valerian C,Harvey Adrian,Pasieka Janice L,Kline Gregory A
BMC endocrine disorders
BACKGROUND:A published clinical prediction score indicated that a unilateral adrenal adenoma and either hypokalemia or an estimated glomerular filtration rate of 100 ml/min/1.73 m2 was 100% specific for unilateral primary aldosteronism. This study aimed to validate this score in a separate cohort of patients with primary aldosteronism. METHODS:A review of patients with primary aldosteronism from June 2005 to July 2013 at a single center's hypertension clinic. One hundred twelve patients with primary aldosteronism underwent successful adrenal vein sampling and the 110 patients with full data available were included in the final analysis. Adrenal vein sampling was performed all patients desiring surgery by the simultaneous collection of sample prior to and 15 minutes after a cosyntropin infusion with a 3:1 aldosterone/cortisol ratio diagnosing unilateral primary aldosteronism. The derived score was applied to the cohort. Sensitivity and specificity were calculated for clinical prediction score of ≥5 points. RESULTS:There were 64 patients found to have unilateral primary aldosteronism and 48 had bilateral disease. A score ≥5 points had 64% sensitivity (95% confidence interval, 51-76) and 85% specificity (95% confidence interval, 71-94) for unilateral disease. Four patients had lateralization of primary aldosteronism to the side contralateral to the adenoma. CONCLUSIONS:The 100% specificity of the score for the unilateral origin of primary aldosteronism was not validated in this cohort with a score of ≥5 points. At best, a high score in this prediction rule may be an additional tool for helping to confirm a decision to offer patients adrenal vein sampling.
Primary aldosteronism subtype discordance between computed tomography and adrenal venous sampling.
Aono Daisuke,Kometani Mitsuhiro,Karashima Shigehiro,Usukura Mikiya,Gondo Yuko,Hashimoto Atsushi,Demura Masashi,Furukawa Kenji,Takeda Yoshiyu,Kawashiri Masaaki,Yoneda Takashi
Hypertension research : official journal of the Japanese Society of Hypertension
The primary aldosteronism (PA) subtype is usually confirmed by CT and adrenal venous sampling (AVS). However, the subtype diagnosis by AVS is not necessarily consistent with the subtype diagnosis by CT. Patients with PA who show bilateral lesions (normal-appearing adrenals or bilateral adrenal nodules) on CT but unilateral disease on AVS are often found. The aim of this study was to evaluate whether patients with PA subtype discordance between CT and AVS obtain benefits from unilateral adrenalectomy. We retrospectively analyzed 362 consecutive patients with PA who underwent both CT and adrenocorticotropic hormone-unstimulated AVS at Kanazawa University Hospital. Surgical outcomes for unilateral PA were evaluated according to the criteria of the Primary Aldosteronism Surgical Outcome study. In our study, the success rate of AVS in patients with bilateral lesions on CT was 89% (191/214). Furthermore, the discordance rate between CT and AVS in patients with bilateral lesions on CT was 39% (74/191). After surgery, patients with bilateral lesions on CT but unilateral disease on AVS (n = 17) had a lower complete biochemical success rate than those with unilateral lesions on CT and ipsilateral disease on AVS (n = 30) (41% vs. 80%, p = 0.01), but clinical and biochemical benefits (the complete and partial success combined) were not significantly different between them (76% vs. 93% (p = 0.11) and 70% vs. 90% (p = 0.10), respectively). In conclusion, patients with bilateral lesions on CT but unilateral disease on AVS benefited from surgery, and AVS should be performed for patients who pursue surgical management when the CT findings suggest bilateral lesions.
A combination of captopril challenge test after saline infusion test improves diagnostic accuracy for primary aldosteronism.
Lin Chuan,Yang Jun,Fuller Peter J,Jing Huan,Song Ying,He Wenwen,Du Zhipeng,Luo Ting,Cheng Qingfeng,Yang Shumin,Wang Hongman,Li Qifu,Hu Jinbo,
CONTEXT:The saline infusion test (SIT) is a common confirmatory test for primary aldosteronism (PA). According to the guideline, a postinfusion plasma aldosterone concentration (PAC) of 5-10 ng/dL is considered indeterminate, and recommendations for diagnostic strategies are currently limited in this situation. OBJECTIVE:To explore whether an addition of the captopril challenge test (CCT) could improve the diagnostic accuracy in patients with indeterminate SIT. METHODS:A total of 280 hypertensive patients with high risk of PA completed this study. Subjects were defined as SIT indeterminate based on their PAC post-SIT. These patients then underwent the CCT where PACs post-CCT >11 ng/dL were considered positive. Using fludrocortisone suppression test (FST) as the reference standard, diagnostic parameters including area under the receiver-operator characteristic curves (AUC), sensitivity and specificity were calculated. RESULTS:There were 65 subjects (23.2%) diagnosed as PA indeterminate after SIT. With the addition of CCT, true-positive numbers increased from 134 to 147, and false-negative numbers decreased from 27 to 14. Compared to SIT alone, a combination of SIT and CCT showed a higher AUC (0.91 [0.87,0.94] vs 0.87 [0.83,0.91], P = .041) and an increased sensitivity for the diagnosis of PA (0.91 [0.86,0.95] vs 0.83 [0.76,0.89], P = .028), while the specificity remained similar. In the subgroup with indeterminate SIT results, using PAC post-CCT resulted in a 36% higher AUC than using PAC post-SIT alone for the diagnosis of PA. CONCLUSION:For patients under investigation for possible PA who have indeterminate SIT results, an addition of CCT improves the diagnostic accuracy.
Prediction of unilateral hyperaldosteronism on adrenal vein sampling using captopril challenge test in patients with primary aldosteronism.
Wada Norio,Miyoshi Arina,Usubuchi Hiroaki,Terae Satoshi,Shibayama Yui,Takahashi Bunya,Baba Shuhei,Sugawara Hajime,Obara Shinji
Captopril challenge test (CCT) is a simple and safe confirmatory test for primary aldosteronism (PA). We investigated the effectiveness of the indices after captopril administration for prediction of unilateral hyperaldosteronism (UHA) on adrenal vein sampling (AVS). We studied 238 patients with PA who had CCT and successful AVS between July 2007 and December 2019 in Sapporo City General Hospital. Receiver operating characteristic (ROC) curve analysis showed that the diagnostic performance for prediction of UHA on AVS in regard to the reduction rate of plasma aldosterone concentration (PAC) after captopril administration was inferior to aldosterone to renin ratio (ARR) and PAC (area under the ROC curve 0.72 vs. 0.84, 0.72 vs. 0.89, respectively, both p < 0.01). Based on the optimal cut-off values in ARR (897 pg/mL/ng/mL/h, sensitivity 64.6%, specificity 93.0%) and PAC (203 pg/mL, sensitivity 73.9%, specificity 93.0%) after captopril administration, the patients were divided into three groups: (1) both positive, (2) one positive, and (3) both negative. The prevalence of UHA on AVS in the three groups were 90.0%, 52.9%, and 7.3%, respectively. In the first group, 31 of 32 patients with unilateral nodular lesion on CT had an ipsilateral unilateral AVS. In conclusion, the combination of post-captopril ARR and PAC is useful for prediction of laterality diagnosis on AVS. AVS is strongly recommended in patients with both positive or one positive results for the optimal cut-off values of post-captopril ARR and PAC and is weakly recommended in patients with both negative results.
Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial.
Dekkers Tanja,Prejbisz Aleksander,Kool Leo J Schultze,Groenewoud Hans J M M,Velema Marieke,Spiering Wilko,Kołodziejczyk-Kruk Sylwia,Arntz Mark,Kądziela Jacek,Langenhuijsen Johannes F,Kerstens Michiel N,van den Meiracker Anton H,van den Born Bert-Jan,Sweep Fred C G J,Hermus Ad R M M,Januszewicz Andrzej,Ligthart-Naber Alike F,Makai Peter,van der Wilt Gert-Jan,Lenders Jacques W M,Deinum Jaap,
The lancet. Diabetes & endocrinology
BACKGROUND:The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism. METHODS:In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654. FINDINGS:We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3·0 [IQR 1·0-5·0] vs 3·0 [1·1-5·9], p=0·52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0·87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0·82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52·7 [IQR 43·9-56·8] vs 53·2 [44·0-56·8], p=0·83; RAND-36 mental scores 49·8 [43·1-54·6] vs 52·7 [44·9-55·5], p=0·17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0·25). A non-significant mean difference of 0·05 (95% CI -0·04 to 0·13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of €2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of €30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0·2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment. INTERPRETATION:Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism. FUNDING:Netherlands Organisation for Health Research and Development-Medical Sciences, Institute of Cardiology, Warsaw.
Seated Saline Suppression Test Is Comparable With Captopril Challenge Test for the Diagnosis of Primary Aldosteronism: A Prospective Study.
Liu Bin,Hu Jinbo,Song Ying,He Wenwen,Cheng Qingfeng,Wang Zhihong,Feng Zhengping,Du Zhipeng,Xu Zhixin,Yang Jun,Li Qifu,Yang Shumin,
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
OBJECTIVE:The saline suppression test (SST) and captopril challenge test (CCT) are commonly used confirmatory tests for primary aldosteronism (PA). Seated SST (SSST) has been reported to be superior to recumbent SST. Whether SSST is better than CCT remains unclear. We aimed to compare the diagnostic accuracy of SSST and CCT in a prospective study. METHODS:Hypertensive patients at a high risk of PA were consecutively included. Patients with an aldosterone-renin ratio of ≥1.0 ng/dL/μIU/mL were asked to complete SSST, CCT, and the fludrocortisone suppression test (FST). Using FST as a reference standard (plasma aldosterone concentration [PAC] post FST ≥ 6.0 ng/dL), area under the receiver-operating characteristic curve (AUC), sensitivity, and specificity of SSST and CCT were calculated, and multiple regression analyses were performed to identify potential factors leading to false diagnosis. RESULTS:A total of 196 patients diagnosed with PA and 73 with essential hypertension completed the study. Using PAC post SSST and PAC post CCT to confirm PA, SSST and CCT had comparable AUCs (AUC 0.87 [95% CI 0.82-0.91] vs AUC 0.88 [0.83-0.95], P = .646). When PAC post SSST and post CCT were set at 8.5 and 11 ng/dL, respectively, the sensitivity and specificity of SSST (0.72 [0.65, 0.78] and 0.86 [0.76, 0.93]) and CCT (0.73 [0.67, 0.80] and 0.85 [0.75, 0.92]) were not significantly different. In the multiple regression analyses, 1-SD increment of sodium intake resulted in a 40% lower risk of false diagnosis with SSST. CONCLUSION:SSST and CCT have comparable diagnostic accuracy. Insufficient sodium intake decreases the diagnostic efficiency of SSST but not of CCT. Since CCT is simpler and cheaper, it is preferred over SSST.
Plasma Aldosterone After Seated Saline Infusion Test Outperforms Captopril Test at Predicting Clinical Outcomes After Adrenalectomy for Primary Aldosteronism.
Wu Che-Hsiung,Wu Vincent,Yang Ya-Wen,Lin Yen-Hung,Yang Shao-Yu,Lin Po-Chih,Chang Chin-Chen,Tsai Yao-Chou,Wang Shuo-Meng,
American journal of hypertension
OBJECTIVE:The saline infusion test (SIT) and the captopril test (CT) are widely used as confirmatory tests for primary aldosteronism (PA). We hypothesized that post-SIT and post-CT plasma aldosterone concentrations (PAC) indicate the severity of aldosterone-producing adenoma (APA) and might predict clinical outcome. METHODS:We recruited 216 patients with APA in the Taiwan Primary Aldosteronism Investigation (TAIPAI) registry who received both seated SIT and CT as confirmatory tests. The data of 143 patients who underwent adrenalectomy with complete follow-up after diagnosis were included in the final analysis. We determined the proportion of patients achieving clinical success in accordance with the Primary Aldosteronism Surgical Outcome consensus. Logistic regression analysis was conducted to identify preoperative factors associated with cure of hypertension. RESULTS:Complete clinical success was achieved in 48 (33.6%) patients and partial clinical success in 59 (41.2%) patients; absent clinical success was seen in 36 (25.2%) of 143 patients. Post-SIT PAC but not post-CT PAC was independently associated with clinical outcome. Higher levels of post-SIT PAC had a higher likelihood of clinical benefit (complete plus partial clinical success; odds ratio = 1.04 per ng/dl increase, 95% confidence interval = 1.01, 1.06; P = 0.004). Patients with post-SIT PAC > 25 ng/dl were more likely to have a favorable clinical outcome after adrenalectomy. This cutoff value translated into a positive predictive value of 86.0%. CONCLUSIONS:We suggest that post-SIT PAC is a better predictor than post-CT PAC for clinical success in PA post adrenalectomy.
Case detection in primary aldosteronism: high-diagnostic value of the aldosterone-to-renin ratio when performed under standardized conditions.
Vorselaars Wessel M C M,Valk Gerlof D,Vriens Menno R,Westerink Jan,Spiering Wilko
Journal of hypertension
OBJECTIVE:The aldosterone-to-renin ratio is widely used and is the recommended screening modality for primary aldosteronism by the Endocrine Society Guideline. However, studies on its diagnostic accuracy have been inconsistent, which is mainly because of methodological limitations. We set out to evaluate this diagnostic value by using a highly standardized study protocol, which is in line with the Endocrine Society Guideline recommendations regarding indications for screening, testing conditions and reference standards in daily clinical practice. METHODS:In this prospective study, 233 consecutive patients referred to the University Medical Center Utrecht with difficult-to-control hypertension were enrolled. In addition to aldosterone-to-renin ratio measurements, all patients underwent a saline infusion test as a reference standard. A plasma aldosterone concentration greater than 280 pmol/l after saline infusion was considered diagnostic for aldosteronism and the plasma renin activity was assessed to exclude patients with secondary aldosteronism from the final primary aldosteronism diagnosis. RESULTS:Correlation of the aldosterone-to-renin ratio (cut-off >5) with primary aldosteronism diagnosis showed 16 true positive, 29 false positive, 188 true negative and 0 false negative aldosterone-to-renin ratios, resulting in a sensitivity of 100% (CI 75.9-100), specificity of 86.7% (CI 81.2-90.7), positive-predictive value of 35.6% (CI 22.3-51.3) and negative-predictive value of 100% (CI 97.5-100.0). The corresponding area under the curve was 0.933 (CI 0.900-0.966). CONCLUSION:These findings show that the aldosterone-to-renin ratio is a good screening modality for primary aldosteronism and is without a high risk of missing a primary aldosteronism diagnosis whenever performed under well standardized conditions.
Screening of primary aldosteronism by clinical features and daily laboratory tests: combination of urine pH, sex, and serum K.
Yamashita Tomohisa,Shimizu Sayaka,Koyama Masayuki,Ohno Kouhei,Mita Tomohiro,Tobisawa Toshiyuki,Takada Akifumi,Togashi Nobuhiko,Ohnuma Yoshito,Hasegawa Tohru,Tsuchida Akihito,Endo Toshiaki,Ando Toshiaki,Yoshida Hideaki,Fukuma Shingo,Fukuhara Shunichi,Moniwa Norihito,Miura Tetsuji
Journal of hypertension
OBJECTIVE:To develop and validate a scoring system for selection of patients who should proceed to endocrinologic examinations of primary aldosteronism in newly diagnosed hypertensive patients. METHODS:A multivariate logistic regression analysis for primary aldosteronism was undertaken by use of seven possible primary aldosteronism markers, age less than 40 years, female sex, moderate-to-severe hypertension, hypokalemia, serum Na minus Cl at least 40 mmol/l, serum uric acid 237.92 μmol/l or less (4.0 mg/dl), and urine pH (U-pH) at least 7.0, in consecutive outpatients newly diagnosed with hypertension. The diagnostic criteria of primary aldosteronism were plasma aldosterone concentration-to-plasma renin activity ratio [ARR, (ng/dl)/(ng/ml per h)] at least 20 and at least one positive result in four types of challenge tests. RESULTS:Of 130 patients, 24 were diagnosed with primary aldosteronism. The area under the receiver operating characteristic curve (AUC) for a logistic model incorporating all possible primary aldosteronism markers was 0.73 [95% confidence interval (CI): 0.61-0.85]. Removing high U-pH, female sex, and hypokalemia from the full model decreased the AUC by 0.059, 0.035, and 0.011, respectively. We devised pH of urine, female sex, low serum K (PFK) score, in which one point each was assigned to high U-pH, female sex, and hypokalemia. The prevalences of primary aldosteronism in patients with 0, 1, 2, and 3 points were 11, 14, 42, and 60%, respectively. In external validation datasets (n = 106), AUC of PFK score was significantly higher than that of hypokalemia alone (0.73, 95% CI: 0.63-0.83 vs. 0.53, 95% CI: 0.44-0.63, P < 0.01). CONCLUSION:PFK score may be a better parameter than hypokalemia alone for identifying patients with a high probability of having primary aldosteronism.
The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism.
Burrello Jacopo,Burrello Alessio,Stowasser Michael,Nishikawa Tetsuo,Quinkler Marcus,Prejbisz Aleksander,Lenders Jacques W M,Satoh Fumitoshi,Mulatero Paolo,Reincke Martin,Williams Tracy Ann
Annals of surgery
OBJECTIVE:To develop a prediction model for clinical outcomes after unilateral adrenalectomy for unilateral primary aldosteronism. SUMMARY BACKGROUND DATA:Unilateral primary aldosteronism is the most common surgically curable form of endocrine hypertension. Surgical resection of the dominant overactive adrenal in unilateral primary aldosteronism results in complete clinical success with resolution of hypertension without antihypertensive medication in less than half of patients with a wide between-center variability. METHODS:A linear discriminant analysis model was built using data of 380 patients treated by adrenalectomy for unilateral primary aldosteronism to classify postsurgical clinical outcomes. The total cohort was then randomly divided into training (280 patients) and test (100 patients) datasets to create and validate a score system to predict clinical outcomes. An online tool (Primary Aldosteronism Surgical Outcome predictor) was developed to facilitate the use of the predictive score. RESULTS:Six presurgical factors associated with complete clinical success (known duration of hypertension, sex, antihypertensive medication dosage, body mass index, target organ damage, and size of largest nodule at imaging) were selected based on classification performance in the linear discriminant analysis model. A 25-point predictive score was built with an optimal cut-off of greater than 16 points (accuracy of prediction = 79.2%; specificity = 84.4%; sensitivity = 71.3%) with an area under the curve of 0.839. CONCLUSIONS:The predictive score and the primary aldosteronism surgical outcome predictor can be used in a clinical setting to differentiate patients who are likely to be clinically cured after surgery from those who will need continuous surveillance after surgery due to persistent hypertension.
Left-versus-right-adrenal-volume ratio as a screening index before adrenal venous sampling to identify unilateral primary aldosteronism patients.
Li Sicheng,Sun Huaiqiang,Ma Lifen,Zhu Yuchun,Xie Wei,Sun Jiayu,Zhao Lianling,Qing Bin,Ren Yan,Tian Haoming,Chen Tao
Journal of hypertension
OBJECTIVES:The current study aimed to investigate the value of the computed tomography-based left-versus-right adrenal gland volume ratio (L/Rv) in screening patients with unilateral primary aldosteronism. METHODS:The current study recruited 114 patients who underwent successful adrenal venous sampling (AVS) and adrenal computed tomography at West China Hospital of Sichuan University. The patients were divided into three groups according to the AVS results: AVS-left, AVS-bilateral, and AVS-right primary aldosteronism. The volumes of the left and right adrenal glands were semiautomatically calculated. The L/Rv of each patient was computed, and its value in identifying unilateral primary aldosteronism was analyzed. RESULTS:The mean value of the L/Rv was larger in AVS-left patients and smaller in AVS-right patients than that in AVS-bilateral patients. In AVS-left primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.344 [area under the curve (AUC) 0.851, sensitivity 80.0%, specificity 78.1%]. The optimal cutoff value was 1.908, of which 46.0% (23/50) of AVS-left primary aldosteronism patients could be identified (specificity 100.0%). In AVS-right primary aldosteronism patients, the cutoff value of the L/Rv with the highest Youden index was 1.267 (AUC 0.868, specificity 72.8%, sensitivity 87.9%). The optimal cutoff value was 0.765, of which 27.3% (9/33) of AVS-right primary aldosteronism patients could be identified (specificity 100.0%). Patients with L/Rv more than 1.908 or less than 0.765 had higher complete success rate postsurgery. CONCLUSION:Although not perfect, the L/Rv is an applicable index to screen unilateral primary aldosteronism patients for surgery. Primary aldosteronism patients, even those aged more than 35 years, with an L/Rv more than 1.908 or less than 0.765 can be spared AVS before surgery.
Development of a Prediction Score to Avoid Confirmatory Testing in Patients With Suspected Primary Aldosteronism.
Burrello Jacopo,Amongero Martina,Buffolo Fabrizio,Sconfienza Elisa,Forestiero Vittorio,Burrello Alessio,Adolf Christian,Handgriff Laura,Reincke Martin,Veglio Franco,Williams Tracy Ann,Monticone Silvia,Mulatero Paolo
The Journal of clinical endocrinology and metabolism
CONTEXT:The diagnostic work-up of primary aldosteronism (PA) includes screening and confirmation steps. Case confirmation is time-consuming, expensive, and there is no consensus on tests and thresholds to be used. Diagnostic algorithms to avoid confirmatory testing may be useful for the management of patients with PA. OBJECTIVE:Development and validation of diagnostic models to confirm or exclude PA diagnosis in patients with a positive screening test. DESIGN, PATIENTS, AND SETTING:We evaluated 1024 patients who underwent confirmatory testing for PA. The diagnostic models were developed in a training cohort (n = 522), and then tested on an internal validation cohort (n = 174) and on an independent external prospective cohort (n = 328). MAIN OUTCOME MEASURE:Different diagnostic models and a 16-point score were developed by machine learning and regression analysis to discriminate patients with a confirmed diagnosis of PA. RESULTS:Male sex, antihypertensive medication, plasma renin activity, aldosterone, potassium levels, and the presence of organ damage were associated with a confirmed diagnosis of PA. Machine learning-based models displayed an accuracy of 72.9%-83.9%. The Primary Aldosteronism Confirmatory Testing (PACT) score correctly classified 84.1% at training and 83.9% or 81.1% at internal and external validation, respectively. A flow chart employing the PACT score to select patients for confirmatory testing correctly managed all patients and resulted in a 22.8% reduction in the number of confirmatory tests. CONCLUSIONS:The integration of diagnostic modeling algorithms in clinical practice may improve the management of patients with PA by circumventing unnecessary confirmatory testing.
Development and validation of a novel diagnostic nomogram model to predict primary aldosteronism in patients with hypertension.
Wang Meng-Hui,Li Nan-Fang,Luo Qin,Wang Guo-Liang,Heizhati Mulalibieke,Wang Ling,Wang Lei,Zhang Wei-Wei
PURPOSE:Primary aldosteronism (PA) remains, to a large extent, an under-diagnosed disease. We aimed to develop and validate a novel clinical nomogram to predict PA based on routine biochemical variables including new ones, calcium-phosphorus product. METHODS:Records from 806 patients with hypertension were randomly divided into 70% (n = 564) as the training set and the remaining 30% (n = 242) as the validation set. Predictors for PA were extracted to construct a nomogram model based on regression analysis of the training set. An internal validation was performed to assess the nomogram model's discrimination and consistency using the area under the curve for receiver operating characteristic curves and calibration plots. The diagnostic accuracy was compared between nomogram and other known prediction models, using receiver operating characteristics (ROC) and decision curve analyses (DCA). RESULTS:Female gender, serum potassium, serum calcium-phosphorus product, and urine pH were adopted as predictors in the nomogram. The nomogram resulted in an area under the curve of 0.73 (95% confidence interval: 0.68-0.78) in the training set and an area under the curve of 0.68 (0.59-0.75) in the validation set. Predicted probability and actual probability matched well in the nomogram (p > 0.05). Based on ROC and DCA, 21-70% threshold to predict PA in the nomogram model was clinically useful. CONCLUSIONS:We have developed a novel nomogram to predict PA in hypertensive individuals based on routine biochemical variables. External validation is needed to further demonstrate its predictive ability in primary care settings.
Development and Validation of Criteria for Sparing Confirmatory Tests in Diagnosing Primary Aldosteronism.
Wang Kanran,Hu Jinbo,Yang Jun,Song Ying,Fuller Peter J,Hashimura Hikaru,He Wenwen,Feng Zhengping,Cheng Qingfeng,Du Zhipeng,Wang Zhihong,Ma Linqiang,Yang Shumin,Li Qifu
The Journal of clinical endocrinology and metabolism
CONTEXT:The Endocrine Society Guidelines for the diagnosis of primary aldosteronism (PA) suggest that confirmatory tests (CFT) are not required when the following criteria are met: plasma aldosterone concentration (PAC) is >20 ng/dL, plasma renin is below detection levels, and hypokalemia is present. The evidence for the applicability of the guideline criteria is limited. OBJECTIVE:To develop and validate optimized criteria for sparing CFT in the diagnosis of PA. DESIGN AND SETTING:The optimized criteria were developed in a Chinese cohort using the captopril challenge test, verified by saline infusion test (SIT) and fludrocortisone suppression test (FST), and validated in an Australian cohort. PARTICIPANTS:Hypertensive patients who completed PA screening and CFT. MAIN OUTCOME MEASURE:Diagnostic value of the optimized criteria. RESULTS:In the development cohort (518 PA and 266 non-PA), hypokalemia, PAC, and plasma renin concentration (PRC) were selected as diagnostic indicators by multivariate logistic analyses. The combination of PAC >20 ng/dL plus PRC <2.5 μIU/mL plus hypokalemia had much higher sensitivity than the guideline criteria (0.36 vs 0.11). The optimized criteria remained superior when the SIT or FST were used as CFT. Non-PA patients were not misdiagnosed by either criteria, but the percentage of patients in whom CFT could be spared was higher with the optimized criteria. In the validation cohort (125 PA and 81 non-PA), the sensitivity of the optimized criteria was also significantly higher (0.12 vs 0.02). CONCLUSIONS:Hypertensive patients with PAC >20 ng/dL, PRC <2.5 μIU/mL, plus hypokalemia can be confidently diagnosed with PA without confirmatory tests.
Should Adrenal Venous Sampling Be Performed in PA Patients Without Apparent Adrenal Tumors?
Okamoto Kentaro,Ohno Youichi,Sone Masakatsu,Inagaki Nobuya,Ichijo Takamasa,Yoneda Takashi,Tsuiki Mika,Wada Norio,Oki Kenji,Tamura Kouichi,Kobayashi Hiroki,Izawa Shoichiro,Tanabe Akiyo,Naruse Mitsuhide
Frontiers in endocrinology
Introduction:Some aldosterone-producing micro-adenomas cannot be detected through image inspection. Therefore, adrenal venous sampling (AVS) is often performed, even in primary aldosteronism (PA) patients who have no apparent adrenal tumors (ATs) on imaging. In most of these cases, however, the PA is bilateral. Objective:To clarify the clinical need for AVS in PA patients without apparent ATs, taking into consideration the rates of adrenalectomy. Methods:This is a retrospective cross-sectional study assessing 1586 PA patients without apparent ATs in the multicenter Japan PA study (JPAS). We analyzed which parameters could be used to distinguish unilateral PA patients without apparent ATs from bilateral patients. We also analyzed the prevalences of adrenalectomy in unilateral PA patients. Results:The unilateral subtype without an apparent AT was diagnosed in 200 (12.6%) of 1586 PA patients. Being young and female with a short hypertension duration, normokalemia, low creatinine level, low plasma aldosterone concentration, and low aldosterone-to-renin ratio (ARR) was significantly more common in bilateral than unilateral PA patients. If PA patients without apparent ATs were female and normokalemic with a low ARR (<560 pg/ml per ng/ml/h), the rate of unilateral PA was only 5 (1.1%) out of 444. Moreover, 77 (38.5%) of the 200 did not receive adrenalectomy, despite being diagnosed with the unilateral subtype based on AVS. Conclusion:The low prevalence of the unilateral subtype in PA patients without apparent ATs suggests AVS is not indicated for all of these patients. AVS could be skipped in female normokalemic PA patients without apparent ATs if their ARRs are not high. However, AVS should be considered for male hypokalemic PA patients with high ARRs because the rates of the unilateral subtype are high in these patients.
THE POTENTIAL CLINICAL APPLICATION OF A LOWER BILATERAL ADRENAL LIMB WIDTH RATIO (L/RW) IN PATIENTS WITH BILATERAL PRIMARY HYPERALDOSTERONISM.
Li Sicheng,Ren Yan,Zhu Yuchun,Sun Huaiqiang,Ma Lifen,Tian Haoming,Chen Tao
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
This study investigated the characteristics of the adrenal limbs of primary aldosteronism (PA) patients and evaluated the value of the adrenal limb width measurement for the differentiation of unilateral PA from bilateral PA. A total of 122 PA patients (93 unilateral PA, ages ranged from 23 to 72 years; 29 bilateral PA, ages ranged from 30 to 68 years) who had undergone successful adrenal venous sampling (AVS) and adrenal gland computed tomography (CT) scan were retrospectively included. The maximum width of each adrenal gland limb (normal area on CT images) was measured, the left adrenal limb width to right adrenal limb width ratio (L/Rw) was calculated, and its potential value in the differentiation of unilateral PA and bilateral PA was analyzed. The mean widths of the left adrenal limbs and the right adrenal limbs were 0.52 ± 0.10 cm and 0.43 ± 0.09 cm in unilateral PA patients, versus 0.52 ± 0.10 cm and 0.49 ± 0.12 cm in bilateral PA patients. The L/Rw ratio was 1.22 ± 0.24 in unilateral PA patients and 1.11 ± 0.23 in bilateral PA patients (<.05). In the subgroup of PA patients over 55 years of age, compared with AVS, the sensitivity and specificity of the L/Rw ratio at 1.06 for subtype classification were 75% and 82%, respectively. A lower L/Rw ratio, referring to the ratio of the left adrenal limb width to the right adrenal limb width, may be a predictor of bilateral PA, especially in PA patients over 55 years of age. = aldosterone-producing adenoma; = adrenal venous sampling; = bilateral adrenal hyperplasia; = body mass index; = computed tomography; = ratio of left adrenal limb width to right adrenal limb width; = primary aldosteronism.
Significance of Discordant Results Between Confirmatory Tests in Diagnosis of Primary Aldosteronism.
Fukumoto Tazuru,Umakoshi Hironobu,Ogata Masatoshi,Yokomoto-Umakoshi Maki,Matsuda Yayoi,Motoya Misato,Nagata Hiromi,Nakano Yui,Iwahashi Norifusa,Kaneko Hiroki,Wada Norio,Miyazawa Takashi,Sakamoto Ryuichi,Ogawa Yoshihiro
The Journal of clinical endocrinology and metabolism
CONTEXT:Current clinical guidelines recommend confirmation of a positive result in at least one confirmatory test in the diagnosis of primary aldosteronism (PA). Clinical implication of multiple confirmatory tests has not been established, especially when patients show discordant results. OBJECTIVE:The aim of the present study was to explore the role of 2 confirmatory tests in subtype diagnosis of PA. DESIGN AND SETTING:A retrospective cross-sectional study was conducted at two referral centers. PARTICIPANTS AND METHODS:We identified 360 hypertensive patients who underwent both a captopril challenge test (CCT) and a saline infusion test (SIT) and exhibited at least one positive result. Among them, we studied 193 patients with PA whose data were available for subtype diagnosis based on adrenal vein sampling (AVS). MAIN OUTCOME MEASURE:The prevalence of bilateral subtype on AVS according to the results of the confirmatory tests was measured. RESULTS:Of patients studied, 127 were positive for both CCT and SIT (double-positive), whereas 66 were positive for either CCT or SIT (single-positive) (n = 34 and n = 32, respectively). Altogether, 135 were diagnosed with bilateral subtype on AVS. The single-positive patients had milder clinical features of PA than the double-positive patients. The prevalence of bilateral subtype on AVS was significantly higher in the single-positive patients than in the double-positive patients. (63/66 [95.5%] vs 72/127 [56.7%], P < .01). Several clinical parameters were different between CCT single-positive and SIT single-positive patients. CONCLUSION:Patients with discordant results between CCT and SIT have a high probability of bilateral subtype of PA on AVS.
Scoring system for the diagnosis of bilateral primary aldosteronism in the outpatient setting before adrenal venous sampling.
Kobayashi Hiroki,Haketa Akira,Ueno Takahiro,Ikeda Yukihiro,Hatanaka Yoshinari,Tanaka Sho,Otsuka Hiromasa,Abe Masanori,Fukuda Noboru,Soma Masayoshi
OBJECTIVE:The only reliable method for subtyping primary aldosteronism (PA) is adrenal venous sampling (AVS), which is costly and time-consuming. Considering the limited availability of AVS, it would be helpful to obtain information on the diagnosis of bilateral hyperaldosteronism (BHA) from routine tests. We aimed to establish new, simple criteria for outpatients to diagnose BHA from PA before AVS. DESIGN:We retrospectively analysed 82 patients who were diagnosed with PA and underwent AVS. Thirty-seven patients were diagnosed with unilateral hyperaldosteronism (UHA), and 36 with BHA and nine were undetermined. Among the variables that were significantly different between UHA and BHA in the univariate analysis, we chose three variables to be included in multivariate logistic regression models and constructed a subtype prediction score. RESULTS:The subtype prediction score was calculated as follows: 3 points for no adrenal nodules on computed tomography imaging, 2 for serum potassium of ≥3·5 mmol/l and 2 for aldosterone-to-renin ratio of <490 after a captopril challenge test. Receiver operating characteristic curve analysis for the ability to discriminate BHA from UHA showed that a score of 7 points had 50% sensitivity and 100% specificity and a score of 5 points had 67% sensitivity and 94% specificity (area under the curve: 0·922; 95% CI: 0·863-0·980). CONCLUSIONS:Our new, simple criteria specifically distinguished BHA from UHA in the outpatient setting before AVS. Furthermore, not only endocrinologists but also general internists can use this convenient, safe scoring system.
Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism.
Eisenhofer Graeme,Dekkers Tanja,Peitzsch Mirko,Dietz Anna S,Bidlingmaier Martin,Treitl Marcus,Williams Tracy A,Bornstein Stefan R,Haase Matthias,Rump L C,Willenberg Holger S,Beuschlein Felix,Deinum Jaap,Lenders Jacques W M,Reincke Martin
BACKGROUND:Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone and cortisol. We assessed the utility of LC-MS/MS-based steroid profiling to stratify patients with primary aldosteronism. METHODS:Fifteen adrenal steroids were measured by LC-MS/MS in peripheral and adrenal venous plasma from AVS studies for 216 patients with primary aldosteronism at 3 tertiary referral centers. Ninety patients were diagnosed with BAH and 126 with APAs on the basis of immunoassay-derived adrenal venous aldosterone lateralization ratios. RESULTS:Among 119 patients confirmed to have APAs at follow-up, LC-MS/MS-derived lateralization ratios of aldosterone normalized to cortisol, dehydroepiandrosterone, and androstenedione were all higher (P < 0.0001) than immunoassay-derived ratios. The hybrid steroids, 18-oxocortisol and 18-hydroxycortisol, also showed lateralized secretion in 76% and 35% of patients with APAs. Adrenal venous concentrations of glucocorticoids and androgens were bilaterally higher in patients with BAH than in those with APAs. Consequently, peripheral plasma concentrations of 18-oxocortisol were 8.5-fold higher, whereas concentrations of cortisol, corticosterone, and dehydroepiandrosterone were lower in patients with APAs than in those with BAH. Correct classification of 80% of cases of APAs vs BAH was thereby possible by use of a combination of steroids in peripheral plasma. CONCLUSIONS:LC-MS/MS-based steroid profiling during AVS achieves higher aldosterone lateralization ratios in patients with APAs than immunoassay. LC-MS/MS also enables multiple measures for discriminating unilateral from bilateral aldosterone excess, with potential use of peripheral plasma for subtype classification.
Significance of adrenal computed tomography in predicting laterality and indicating adrenal vein sampling in primary aldosteronism.
Kamemura K,Wada N,Ichijo T,Matsuda Y,Fujii Y,Kai T,Fukuoka T,Sakamoto R,Ogo A,Suzuki T,Umakoshi H,Tsuiki M,Naruse M
Journal of human hypertension
Although laterality assessed by computed tomography (CT) in primary aldosteronism (PA) is not always concordant with that assessed by adrenal vein sampling (AVS), it is unclear whether all patients diagnosed with PA should undergo AVS for subtype classification. The aim of the current study was to investigate the accuracy of CT in subtype classification and to develop a prediction score for bilateral subtype in patients without adrenal tumour. As part of the WAVES-J study, 393 patients with PA were analysed. Subtyping using CT was concordant with that using AVS in 68% (269/393) of patients in the total sample, and in 38% (68/156) of patients with unilateral tumours, 56% (5/9) of patients with bilateral tumours and 89% (204/228) of patients without tumour. In patients without tumour, female gender, plasma aldosterone concentration (pg ml) to plasma renin activity ratio ⩽550 and serum potassium ⩾3.8 mEq l were shown to be independent predictors for bilateral subtype. A prediction score based on these three variables was constructed with one point attributed to each variable. A score of three points had 29% sensitivity and 96% specificity in a receiver operating characteristic curve analysis. The results suggest that although CT is not sufficiently accurate for subtype classification in patients with adrenal tumours, it is sufficient to determine bilateral subtype in patients without tumour. Moreover, using our clinical prediction score in patients without tumour could be useful in determining the necessity of AVS for subtype classification.
Machine learning based models for prediction of subtype diagnosis of primary aldosteronism using blood test.
Kaneko Hiroki,Umakoshi Hironobu,Ogata Masatoshi,Wada Norio,Iwahashi Norifusa,Fukumoto Tazuru,Yokomoto-Umakoshi Maki,Nakano Yui,Matsuda Yayoi,Miyazawa Takashi,Sakamoto Ryuichi,Ogawa Yoshihiro
Primary aldosteronism (PA) is associated with an increased risk of cardiometabolic diseases, especially in unilateral subtype. Despite its high prevalence, the case detection rate of PA is limited, partly because of no clinical models available in general practice to identify patients highly suspicious of unilateral subtype of PA, who should be referred to specialized centers. The aim of this retrospective cross-sectional study was to develop a predictive model for subtype diagnosis of PA based on machine learning methods using clinical data available in general practice. Overall, 91 patients with unilateral and 138 patients with bilateral PA were randomly assigned to the training and test cohorts. Four supervised machine learning classifiers; logistic regression, support vector machines, random forests (RF), and gradient boosting decision trees, were used to develop predictive models from 21 clinical variables. The accuracy and the area under the receiver operating characteristic curve (AUC) for predicting of subtype diagnosis of PA in the test cohort were compared among the optimized classifiers. Of the four classifiers, the accuracy and AUC were highest in RF, with 95.7% and 0.990, respectively. Serum potassium, plasma aldosterone, and serum sodium levels were highlighted as important variables in this model. For feature-selected RF with the three variables, the accuracy and AUC were 89.1% and 0.950, respectively. With an independent external PA cohort, we confirmed a similar accuracy for feature-selected RF (accuracy: 85.1%). Machine learning models developed using blood test can help predict subtype diagnosis of PA in general practice.
A subtype prediction score for primary aldosteronism.
Nanba K,Tsuiki M,Nakao K,Nanba A,Usui T,Tagami T,Hirokawa Y,Okuno H,Suzuki T,Shimbo T,Shimatsu A,Naruse M
Journal of human hypertension
Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Although adrenal venous sampling (AVS) is recommended as the gold standard procedure for subtype classification in PA, it is a specialized technique with limited availability. The objective of this study was to develop a scoring system that predicted PA subtype using clinical characteristics. Seventy-one patients with PA were studied. The subjects were diagnosed as having either unilateral (n=32) or bilateral disease (n=39) based on AVS, surgery and/or the postoperative clinical course. Variables associated with laterality in the univariate analysis were entered into multivariable logistic regression models and the regression coefficients were used to construct a subtype prediction score. The diagnostic significance of the score was then evaluated using receiver operating characteristic (ROC) curve analysis. The subtype prediction score was calculated as follows: serum potassium ⩽3.4 mEq l(-1), 2 points; plasma aldosterone concentration ⩾165 pg ml(-1), 3 points; and aldosterone to renin ratio ⩾1000 in a post-captopril challenge test (plasma renin activity in ng ml(-1) h(-1)), 3 points. ROC curve analysis for the ability to discriminate between unilateral and bilateral PA showed that a score of 5 points had 75% sensitivity and 95% specificity, and a score of 3 points had a sensitivity of 97% and a specificity of 59%. The area under the ROC curve was 0.920 (95% confidence interval, 0.859-0.979). Our subtype prediction score could discriminate between unilateral and bilateral PA and is useful for selecting patients who should undergo AVS before surgery.
Diagnostic Accuracy of Computed Tomography in Predicting Primary Aldosteronism Subtype According to Age.
Lee Seung Hun,Kim Jong Woo,Yoon Hyun-Ki,Koh Jung-Min,Shin Chan Soo,Kim Sang Wan,Kim Jung Hee
Endocrinology and metabolism (Seoul, Korea)
BACKGROUND:Guidelines by the Endocrine Society Guideline on bypassing adrenal vein sampling (AVS) in patients <35 years old with marked primary aldosteronism (PA) (hypokalemia and elevated plasma aldosterone concentration [PAC]) and a unilateral lesion on computed tomography (CT) are based on limited number of studies. We aimed to determine the accuracy of CT in PA patients according to age. METHODS:In this retrospective study, we investigated the concordance between CT and AVS in 466 PA patients from two tertiary centers who successfully underwent AVS. RESULTS:CT had an overall accuracy of 64.4% (300/466). In the group with unilateral lesion, patients with hypokalemia had higher concordance than those without hypokalemia (85.0% vs. 43.6%, P<0.001). In the group with marked PA (hypokalemia and PAC >15.9 ng/dL) and unilateral lesion, accuracy of CT was 84.6% (11/13) in patients aged <35 years; 100.0% (20/20), aged 35 to 39 years; 89.4% (59/66), aged 40 to 49 years; and 79.8% (79/99), aged ≥50 years. Cut-off age and PAC for concordance was <50 years and >29.6 ng/dL, respectively. The significant difference in accuracy of CT in 198 patients with marked PA and a unilateral lesion between the <50-year age group and ≥50-year age group (90.9% vs. 79.8%, P=0.044) disappeared in 139 of 198 patients with PAC > 30.0 ng/dL (91.9% vs. 87.7%, P=0.590). CONCLUSION:Patients with hypokalemia, PAC >30.0 ng/dL, and unilateral lesion were at high risk of unilateral PA regardless of age.
Classification of microadenomas in patients with primary aldosteronism by steroid profiling.
Yang Yuhong,Burrello Jacopo,Burrello Alessio,Eisenhofer Graeme,Peitzsch Mirko,Tetti Martina,Knösel Thomas,Beuschlein Felix,Lenders Jacques W M,Mulatero Paolo,Reincke Martin,Williams Tracy Ann
The Journal of steroid biochemistry and molecular biology
In primary aldosteronism (PA) the differentiation of unilateral aldosterone-producing adenomas (APA) from bilateral adrenal hyperplasia (BAH) is usually performed by adrenal venous sampling (AVS) and/or computed tomography (CT). CT alone often lacks the sensitivity to identify micro-APAs. Our objectives were to establish if steroid profiling could be useful for the identification of patients with micro-APAs and for the development of an online tool to differentiate micro-APAs, macro-APAs and BAH. The study included patients with PA (n = 197) from Munich (n = 124) and Torino (n = 73) and comprised 33 patients with micro-APAs, 95 with macro-APAs, and 69 with BAH. Subtype differentiation was by AVS, and micro- and macro-APAs were selected according to pathology reports. Steroid concentrations in peripheral venous plasma were measured by liquid chromatography-tandem mass spectrometry. An online tool using a random forest model was built for the classification of micro-APA, macro-APA and BAH. Micro-APA were classified with low specificity (33%) but macro-APA and BAH were correctly classified with high specificity (93%). Improved classification of micro-APAs was achieved using a diagnostic algorithm integrating steroid profiling, CT scanning and AVS procedures limited to patients with discordant steroid and CT results. This would have increased the correct classification of micro-APAs to 68% and improved the overall classification to 92%. Such an approach could be useful to select patients with CT-undetectable micro-APAs in whom AVS should be considered mandatory.
Subtype prediction in primary aldosteronism: measurement of circadian variation of adrenocortical hormones and 24-h urinary aldosterone.
Kobayashi Hiroki,Haketa Akira,Ueno Takahiro,Suzuki Ryo,Aoi Noriko,Ikeda Yukihiro,Tahira Kazunobu,Hatanaka Yoshinari,Tanaka Sho,Otsuka Hiromasa,Abe Masanori,Fukuda Noboru,Soma Masayoshi
OBJECTIVE:Currently, adrenal venous sampling (AVS) is the only reliable method to distinguish unilateral from bilateral hyperaldosteronism in primary aldosteronism (PA). However, AVS is costly and time-consuming compared with simple blood tests. In this study, we conducted a retrospective study to determine whether circadian variation in plasma adrenocortical hormone levels (i.e. aldosterone, cortisol and ACTH) and a 24-h urinary aldosterone could contribute to the clinical differentiation between unilateral hyperaldosteronism (UHA) and bilateral hyperaldosteronism (BHA). DESIGN:In 64 patients who were diagnosed with PA and underwent AVS, 32 and 22 patients were diagnosed with UHA and BHA, respectively. Plasma adrenocortical hormone levels at 0:00, 6:00, 12:00 and 18:00 and 24-h urinary aldosterone under a condition of 6 g daily dietary sodium chloride intake were measured. RESULTS:Baseline plasma aldosterone concentration (PAC) and 24-h urinary aldosterone level in patients with UHA were significantly higher than in patients with BHA, particularly at 6:00. The area under the ROC curve for PAC at 0:00, 6:00, 12:00 and 18:00 and 24-h urinary aldosterone to discriminate UHA and BHA was 0·839 [95% confidence interval (CI); 0·73-0·95], 0·922 (95% CI; 0·85-1·00), 0·875 (95% CI; 0·78-0·97), 0·811 (95% CI; 0·69-0·93), 0·898 (95% CI; 0·81-0·99), respectively. CONCLUSIONS:PAC at different blood sampling times and 24-h urinary aldosterone level may be diagnostically helpful in discriminating between UHA and BHA. We believe that these tests could reduce the number of unnecessary AVS procedures.
Aldosterone Reduction Rate After Saline Infusion Test May Be a Novel Prediction in Patients With Primary Aldosteronism.
Nagano Hidekazu,Kono Takashi,Saiga Atsushi,Kubota Yoshihiro,Fujimoto Masanori,Felizola Saulo J A,Ishiwata Kazuki,Tamura Ai,Higuchi Seiichiro,Sakuma Ikki,Hashimoto Naoko,Suzuki Sawako,Koide Hisashi,Takeshita Nobushige,Sakamoto Shinichi,Ban Toshiaki,Yokote Koutaro,Nakamura Yasuhiro,Ichikawa Tomohiko,Uno Takashi,Tanaka Tomoaki
The Journal of clinical endocrinology and metabolism
OBJECTIVE:Accurate assessment and localization of aldosterone-producing adenomas (APAs) are essential for the treatment of primary aldosteronism (PA). Although adrenal venous sampling (AVS) is the standard method of reference for subtype diagnosis in PA, controversy exists concerning the criteria for its interpretation. This study aims to determine better indicators that can reliably predict subtypes of PA. METHOD:Retrospective, single-cohort analysis including 209 patients with PA who were subjected to AVS. Eighty-two patients whose plasma aldosterone concentrations (PAC) were normalized after surgery were histopathologically or genetically diagnosed with APA. The accuracy of image findings was compared to AVS results. Receiver operating characteristic (ROC) curve analysis between the operated and the no-apparent laterality groups was performed using AVS parameters and loading test for diagnosis of PA. RESULT:Agreement between image findings and AVS results was 56.3%. ROC curve analysis revealed that the lateralization index (LI) after adrenocorticotropin stimulation cutoff was 2.40, with 98.8% sensitivity and 97.1% specificity. The contralateral suppression index (CSI) cutoff value was 1.19, with 98.0% sensitivity and 93.9% specificity. All patients over the LI and CSI cutoff values exhibited unilateral subtypes. Among the loading test, the best classification accuracy was achieved using the PAC reduction rate after a saline infusion test (SIT) >33.8%, which yielded 87.2% sensitivity or a PAC after a SIT <87.9 pg/mL with 86.2% specificity for predicting bilateral PA. CONCLUSION:The combined criteria of the PAC reduction rate and PAC after the SIT can determine which subset of patients with APA who should be performed AVS for validation.
Accuracy of adrenal computed tomography in predicting the unilateral subtype in young patients with hypokalaemia and elevation of aldosterone in primary aldosteronism.
Umakoshi Hironobu,Ogasawara Tatsuki,Takeda Yoshiyu,Kurihara Isao,Itoh Hiroshi,Katabami Takuyuki,Ichijo Takamasa,Wada Norio,Shibayama Yui,Yoshimoto Takanobu,Ogawa Yoshihiro,Kawashima Junji,Sone Masakatsu,Inagaki Nobuya,Takahashi Katsutoshi,Watanabe Minemori,Matsuda Yuichi,Kobayashi Hiroki,Shibata Hirotaka,Kamemura Kohei,Otsuki Michio,Fujii Yuichi,Yamamto Koichi,Ogo Atsushi,Yanase Toshihiko,Okamura Shintaro,Miyauchi Shozo,Suzuki Tomoko,Tsuiki Mika,Naruse Mitsuhide
CONTEXT:The current Endocrine Society Guideline suggests that patients aged <35 years with marked primary aldosteronism (PA) and unilateral adrenal lesions on adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS) before proceeding to unilateral adrenalectomy. This suggestion is, however, based on the data from only one report in the literature. OBJECTIVE:We sought to determine the accuracy of CT findings in young PA patients who had unilateral adrenal disease on CT with hypokalaemia and elevation of aldosterone. DESIGN AND PATIENTS:We retrospectively studied 358 PA patients (n = 30, aged <35 years; n = 39, aged 35-40 years; n = 289, aged ≥40 years) with hypokalaemia and elevation of aldosterone and unilateral disease on CT who had successful AVS. MAIN OUTCOME MEASURE:Accuracy of CT findings is determined by AVS findings and/or surgical outcomes in patients aged <35 years. RESULTS:Concordance of the diagnosis between CT and AVS was 90% (27/30) in patients aged <35 years, 79% (31/39) in patients aged 35-40 years and 69% (198/289) in those aged ≥40 years (trend for P < .01). Surgical benefit was confirmed in three patients aged <35 years and in three patients aged 35-40 years with the available surgical data who had discordance between CT and AVS findings. Collectively, the diagnostic accuracy of CT findings was 100% (30/30) if aged <35 years and 87% (34/39) if aged 35-40 years. CONCLUSION:Primary aldosteronism patients aged <35 years with hypokalaemia and elevation of aldosterone and unilateral disease on adrenal CT could be spared AVS.
Significance of Computed Tomography and Serum Potassium in Predicting Subtype Diagnosis of Primary Aldosteronism.
Umakoshi Hironobu,Tsuiki Mika,Takeda Yoshiyu,Kurihara Isao,Itoh Hiroshi,Katabami Takuyuki,Ichijo Takamasa,Wada Norio,Yoshimoto Takanobu,Ogawa Yoshihiro,Kawashima Junji,Sone Masakatsu,Inagaki Nobuya,Takahashi Katsutoshi,Watanabe Minemori,Matsuda Yuichi,Kobayashi Hiroki,Shibata Hirotaka,Kamemura Kohei,Otsuki Michio,Fujii Yuichi,Yamamto Koichi,Ogo Atsushi,Yanase Toshihiko,Suzuki Tomoko,Naruse Mitsuhide,
The Journal of clinical endocrinology and metabolism
Context:The number of centers with established adrenal venous sampling (AVS) programs for the subtype diagnosis of primary aldosteronism (PA) is limited. Objective:Aim was to develop an algorithm for AVS based on subtype prediction by computed tomography (CT) and serum potassium. Design:A multi-institutional retrospective cohort study in Japan. Patients:A total of 1591 patients with PA were classified into four groups according to CT findings and potassium status. Subtype diagnosis of PA was determined by AVS. Main Outcome Measure:Prediction value of the combination of CT findings and potassium status for subtype diagnosis. Results:The percentages of unilateral hyperaldosteronism on AVS were higher in patients with unilateral disease on CT than those with bilateral normal results on CT (50.8% vs 14.6%, P < 0.01), and these percentages were higher in those with hypokalemia than those with normokalemia (58.4% vs 11.5%, P < 0.01). The prevalence and odds ratio for unilateral hyperaldosteronism on AVS were as follows: bilateral normal on CT with normokalemia, 6.2% (reference); unilateral disease on CT with normokalemia, 23.8% and 4.8 [95% confidence interval (CI), 3.1 to 7.2]; bilateral normal on CT with hypokalemia, 38.1% and 9.4 (95% CI, 6.2 to 14.1), and unilateral disease on CT with hypokalemia, 70.6% and 36.4 (95% CI, 24.7 to 53.5). Conclusions:Patients with PA with bilateral normal results on CT and normokalemia likely have a low prior probability of a lateralized form of AVS and could be treated medically, whereas those with unilateral disease on CT and hypokalemia have a high probability of a lateralized form of AVS.
ACTH stimulation test and computed tomography are useful for differentiating the subtype of primary aldosteronism.
Moriya Ayako,Yamamoto Masaaki,Kobayashi Shunsuke,Nagamine Tomoko,Takeichi-Hattori Naomi,Nagao Mototsugu,Harada Taro,Tanimura-Inagaki Kyoko,Onozawa Shiro,Murata Satoru,Tamura Hideki,Fukuda Izumi,Oikawa Shinichi,Sugihara Hitoshi
The diagnostic steps for primary aldosteronism (PA) include case screening tests, confirmatory tests, and localization. The aim of this study was to identify useful confirmatory tests and their cut-off values for differentiating the subtype of primary aldosteronism, especially in unilateral PA, such as aldosterone-producing adenoma, and bilateral PA, such as idiopathic hyperaldosteronism. Seventy-six patients who underwent all four confirmatory tests, the captopril-challenge test (CCT), furosemide upright test (FUT), saline infusion test (SIT), and ACTH stimulation test (AST), and who were confirmed to have an aldosterone excess by adrenal venous sampling (AVS) were recruited. Subjects were diagnosed as having unilateral aldosterone excess (n=17) or bilateral aldosterone excess (n=59) by AVS. The SIT-positive rate was significantly higher in the unilateral group (94.1%) than in the bilateral group (57.6%). Multivariable logistic regression analysis showed that tumor on computed tomography (CT) and plasma aldosterone concentration (PAC)/cortisol on the AST were useful for differentiating the subtype of PA. Receiver operating characteristic (ROC) curve analysis for distinguishing the subtype of PA showed that a cut-off value of 18.3 PAC/cortisol on the AST had a sensitivity of 83% and a specificity of 88%. The area under the ROC curve was 0.918 (95% confidence interval 0.7916-0.9708). These data suggest that abdominal CT and AST are useful for differentiating the subtype of PA and the indication for AVS.
Seated saline infusion test in predicting subtype diagnosis of primary aldosteronism.
Kaneko Hiroki,Umakoshi Hironobu,Ishihara Yuki,Sugawa Taku,Nanba Kazutaka,Tsuiki Mika,Kusakabe Toru,Satoh-Asahara Noriko,Yasoda Akihiro,Tagami Tetsuya
CONTEXT:Although saline infusion test is widely used as a confirmatory test for primary aldosteronism (PA), it is reportedly less sensitive in patients in whom aldosterone is responsive to the upright position by performing it in recumbent position. Based on a single-centre experience, seated saline infusion test (SSIT) has been reported to be highly sensitive and superior to recumbent testing in identifying both unilateral and bilateral forms of PA. However, due to limited participants number, the utility of SSIT needs to be validated in other series. OBJECTIVE:This study aimed to evaluate the accuracy of SSIT in determining the PA subtypes compared with adrenocorticotropic hormone stimulation test under dexamethasone suppression (Dex-AT). PATIENTS AND SETTING:Sixty-four patients with PA who underwent both SSIT and Dex-AT were included. Subtype diagnosis of PA was determined by adrenal venous sampling (AVS) (16 unilateral and 48 bilateral forms). MAIN OUTCOME MEASURE:Plasma aldosterone concentrations (PACs) were measured after SSIT and Dex-AT. RESULTS:The area under the receiver operating characteristic (ROC) curve for diagnosing unilateral PA was greater in SSIT than that in Dex-AT (0.907 vs. 0.755; P = .023). ROC curve analysis predicted optimal cut-off PACs of 13.1 ng/dL (sensitivity, 93.8%; specificity, 79.2%) for SSIT and 34.2 ng/dL (sensitivity, 75.0%; specificity, 68.8%) for Dex-AT. CONCLUSIONS:Seated saline infusion test has superior accuracy in subtype diagnosis of PA compared with Dex-AT. SSIT can be a sensitive test for determining patients who require AVS prior to surgery.
Aldosterone-potassium ratio predicts primary aldosteronism subtype.
Puar Troy H,Loh Wann J,Lim Dawn St,Loh Lih M,Zhang Meifen,Foo Roger S,Lee Lynette,Swee Du S,Khoo Joan,Tay Donovan,Kam Jia W,Dekkers Tanja,Velema Marieke,Deinum Jaap,Kek Peng C
Journal of hypertension
OBJECTIVE:Prediction models have been developed to predict either unilateral or bilateral primary aldosteronism, and these have not been validated externally. We aimed to develop a simplified score to predict both subtypes and validate this externally. METHODS:Our development cohort was taken from 165 patients who underwent adrenal vein sampling (AVS) in two Asian tertiary centres. Unilateral disease was determined using both AVS and postoperative outcome. Multivariable analysis was used to construct prediction models. We validated our tool in a European cohort of 97 patients enrolled in the SPARTACUS trial who underwent AVS. Previously published prediction models were also tested in our cohorts. RESULTS:Backward stepwise logistic regression analysis yielded a final tool using baseline aldosterone-to-lowest-potassium ratio (APR, ng/dl/mmol/l), with an area under receiver-operating characteristic curve of 0.80 (95% CI 0.70-0.89). In the Asian development cohort, probability of bilateral disease was 90.0% (with APR <5) and probability of unilateral disease was 91.4% (with APR >15). Similar results were seen in the European validation cohort. Combining both cohorts, probability of bilateral disease was 76.7% (with APR <5), and probability for unilateral was 91.7% (with APR >15). Other models had similar predictive ability but required more variables, and were less sensitive for identifying bilateral PA. CONCLUSION:The novel aldosterone-to-lowest-potassium ratio is a convenient score to guide clinicians and patients of various ethnicities on the probability of primary aldosteronism subtype. Using APR to identify patients more likely to benefit from AVS may be a cost-effective strategy to manage this common condition.
Development and validation of subtype prediction scores for the workup of primary aldosteronism.
Kobayashi Hiroki,Abe Masanori,Soma Masayoshi,Takeda Yoshiyu,Kurihara Isao,Itoh Hiroshi,Umakoshi Hironobu,Tsuiki Mika,Katabami Takuyuki,Ichijo Takamasa,Wada Norio,Yoshimoto Takanobu,Ogawa Yoshihiro,Kawashima Junji,Sone Masakatsu,Inagaki Nobuya,Takahashi Katsutoshi,Watanabe Minemori,Matsuda Yuichi,Shibata Hirotaka,Kamemura Kohei,Yanase Toshihiko,Otsuki Michio,Fujii Yuichi,Yamamoto Koichi,Ogo Atsushi,Nanba Kazutaka,Tanabe Akiyo,Suzuki Tomoko,Naruse Mitsuhide,
Journal of hypertension
OBJECTIVES:A subtype prediction score for primary aldosteronism has not yet been developed and validated using a large dataset. This study aimed to develop and validate a new subtype prediction score and to compare it with existing scores using a large multicenter database. METHODS:In total, 1936 patients with primary aldosteronism were randomly assigned to the development and validation datasets, constituting 1290 and 646 patients, respectively. Three prediction scores were generated with or without confirmatory tests, using logistic regression analysis. In the validation dataset, new and existing prediction scores were compared using receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement analyses. RESULTS:The new prediction score is simply calculated using serum potassium levels [>3.9 mmol/l (four points); 3.5-3.9 mmol/l (three points)], the absence of adrenal nodules during computed tomography (three points), a baseline plasma aldosterone concentration of <210.0 pg/ml (two points), a baseline aldosterone/renin ratio of less than 620 (two points), and female sex (one point). Using the validation dataset, we found that a new subtype prediction score of at least 8 had a positive predictive value of 93.5% for bilateral hyperaldosteronism. The new prediction score for bilateral hyperaldosteronism was better than the existing prediction scores in the receiver operating characteristic curve and net reclassification improvement analyses. CONCLUSION:The new prediction score has clear advantages over the existing prediction scores in terms of diagnostic accuracy, feasibility, and the potential for generalization in a large population. These data will help healthcare professionals to better select patients who require adrenal venous sampling.
Development and Validation of Prediction Models for Subtype Diagnosis of Patients With Primary Aldosteronism.
Burrello Jacopo,Burrello Alessio,Pieroni Jacopo,Sconfienza Elisa,Forestiero Vittorio,Rabbia Paola,Adolf Christian,Reincke Martin,Veglio Franco,Williams Tracy Ann,Monticone Silvia,Mulatero Paolo
The Journal of clinical endocrinology and metabolism
CONTEXT:Primary aldosteronism (PA) comprises unilateral (lateralized [LPA]) and bilateral disease (BPA). The identification of LPA is important to recommend potentially curative adrenalectomy. Adrenal venous sampling (AVS) is considered the gold standard for PA subtyping, but the procedure is available in few referral centers. OBJECTIVE:To develop prediction models for subtype diagnosis of PA using patient clinical and biochemical characteristics. DESIGN, PATIENTS AND SETTING:Patients referred to a tertiary hypertension unit. Diagnostic algorithms were built and tested in a training (N = 150) and in an internal validation cohort (N = 65), respectively. The models were validated in an external independent cohort (N = 118). MAIN OUTCOME MEASURE:Regression analyses and supervised machine learning algorithms were used to develop and validate 2 diagnostic models and a 20-point score to classify patients with PA according to subtype diagnosis. RESULTS:Six parameters were associated with a diagnosis of LPA (aldosterone at screening and after confirmatory testing, lowest potassium value, presence/absence of nodules, nodule diameter, and computed tomography results) and were included in the diagnostic models. Machine learning algorithms displayed high accuracy at training and internal validation (79.1%-93%), whereas a 20-point score reached an area under the curve of 0.896, and a sensitivity/specificity of 91.7/79.3%. An integrated flowchart correctly addressed 96.3% of patients to surgery and would have avoided AVS in 43.7% of patients. The external validation on an independent cohort confirmed a similar diagnostic performance. CONCLUSIONS:Diagnostic modelling techniques can be used for subtype diagnosis and guide surgical decision in patients with PA in centers where AVS is unavailable.
A novel clinical nomogram to predict bilateral hyperaldosteronism in Chinese patients with primary aldosteronism.
Xiao Libin,Jiang Yiran,Zhang Cui,Jiang Lei,Zhou Weiwei,Su Tingwei,Ning Guang,Wang Weiqing
CONTEXT:Adrenal venous sampling (AVS) is recommended as the gold standard for subtype classification in primary aldosteronism (PA); however, this approach has limited availability. OBJECTIVE:We aimed to develop a novel clinical nomogram to predict PA subtype based on routine variables, thereby reducing the number of candidates for AVS. PATIENTS AND METHOD:Patients were randomly divided into a training set (n = 185) and a validation set (n = 79). Risk factors for idiopathic hyperaldosteronism (IHA) differentiating from aldosterone-producing adenoma (APA) were identified using logistic regression analysis. A nomogram was constructed to predict the probability of IHA. A receiver operating characteristic (ROC) curve and a calibration plot were applied to assess the predictive value. Then, 115 patients were prospectively enrolled, and a nomogram was used to predict the subtypes before AVS. RESULTS:Body mass index (BMI), serum potassium and computed tomography (CT) finding were adopted in the nomogram. The nomogram presented an area under the ROC (AUC) of 0.924 (95% CI: 0.875-0.957), sensitivity of 86.59% and specificity of 87.38% in the training set and an AUC of 0.894 (95% CI: 0.804-0.952), sensitivity of 82.86% and specificity of 84.09% in the validation set. Predicted probability and actual probability matched well in the nomogram (Hosmer-Lemeshow test: P > 0.05). Using the nomogram as a surrogate to predict IHA in the prospective set before AVS, the specificity reached 100% when we increased the threshold to a probability of 90%. CONCLUSION:We have developed a tool that is able to predict IHA in patients with PA and potentially avoid AVS.
Sex Difference in the Association Between Subtype Distribution and Age at Diagnosis in Patients With Primary Aldosteronism.
Akasaka Hiroshi,Yamamoto Koichi,Rakugi Hiromi,Nagasawa Motonori,Nakamaru Ryo,Ichijo Takamasa,Takeda Yoshiyu,Kurihara Isao,Katabami Takuyuki,Tsuiki Mika,Wada Norio,Ogawa Yoshihiro,Kawashima Junji,Sone Masakatsu,Kamemura Kohei,Yoshimoto Takanobu,Matsuda Yuichi,Fujita Megumi,Kobayashi Hiroki,Watanabe Minemori,Tamura Kouichi,Okamura Shintaro,Miyauchi Shozo,Izawa Shoichiro,Chiba Yoshiro,Tanabe Akiyo,Naruse Mitsuhide,
Hypertension (Dallas, Tex. : 1979)
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Adrenal vein sampling (AVS) is an established method for finding patients with the unilateral subtype of PA, for which adrenalectomy is an applicable treatment. In this study, we analyzed a large database of patients with PA who underwent adrenal vein sampling, to investigate the sex differences in the impact of age at diagnosis on the subtype and cause of PA. In 2122 patients, women with the unilateral subtype were younger than men with the same subtype and women with the bilateral subtype. Younger age and older age were associated with unilateral PA in women and men, respectively. After stratification by tertiles of age, there was a trend of decreased and increased incidence of unilateral PA with aging in women and men, respectively. Male sex was a predictor of unilateral PA in middle-aged and older patients but not in younger patients. We also found that obesity, a known factor associated with idiopathic hyperaldosteronism, was positively associated with bilateral PA in younger patients but not in older patients. These findings suggest that the proportion of operable patients with unilateral PA differs depending on the combination of sex and age, and that other than obesity, the cause of PA is also associated with the bilateral subtype in older patients.
Use of Steroid Profiling Combined With Machine Learning for Identification and Subtype Classification in Primary Aldosteronism.
Eisenhofer Graeme,Durán Claudio,Cannistraci Carlo Vittorio,Peitzsch Mirko,Williams Tracy Ann,Riester Anna,Burrello Jacopo,Buffolo Fabrizio,Prejbisz Aleksander,Beuschlein Felix,Januszewicz Andrzej,Mulatero Paolo,Lenders Jacques W M,Reincke Martin
JAMA network open
Importance:Most patients with primary aldosteronism, a major cause of secondary hypertension, are not identified or appropriately treated because of difficulties in diagnosis and subtype classification. Applications of artificial intelligence combined with mass spectrometry-based steroid profiling could address this problem. Objective:To assess whether plasma steroid profiling combined with machine learning might facilitate diagnosis and treatment stratification of primary aldosteronism, particularly for patients with unilateral adenomas due to pathogenic KCNJ5 sequence variants. Design, Setting, and Participants:This diagnostic study was conducted at multiple tertiary care referral centers. Steroid profiles were measured from June 2013 to March 2017 in 462 patients tested for primary aldosteronism and 201 patients with hypertension. Data analyses were performed from September 2018 to August 2019. Main Outcomes and Measures:The aldosterone to renin ratio and saline infusion tests were used to diagnose primary aldosteronism. Subtyping was done by adrenal venous sampling and follow-up of patients who underwent adrenalectomy. Statistical tests and machine-learning algorithms were applied to plasma steroid profiles. Areas under receiver operating characteristic curves, sensitivity, specificity, and other diagnostic performance measures were calculated. Results:Primary aldosteronism was confirmed in 273 patients (165 men [60%]; mean [SD] age, 51  years), including 134 with bilateral disease and 139 with unilateral adenomas (58 with and 81 without somatic KCNJ5 sequence variants). Plasma steroid profiles varied according to disease subtype and were particularly distinctive in patients with adenomas due to KCNJ5 variants, who showed better rates of biochemical cure after adrenalectomy than other patients. Among patients tested for primary aldosteronism, a selection of 8 steroids in combination with the aldosterone to renin ratio showed improved effectiveness for diagnosis over either strategy alone. In contrast, the steroid profile alone showed superior performance over the aldosterone to renin ratio for identifying unilateral disease, particularly adenomas due to KCNJ5 variants. Among 632 patients included in the analysis, machine learning-designed combinatorial marker profiles of 7 steroids alone both predicted primary aldosteronism in 1 step and subtyped patients with unilateral adenomas due to KCNJ5 variants at diagnostic sensitivities of 69% (95% CI, 68%-71%) and 85% (95% CI, 81%-88%), respectively, and at specificities of 94% (95% CI, 93%-94%) and 97% (95% CI, 97%-98%), respectively. The validation series yielded comparable diagnostic performance. Conclusions and Relevance:Machine learning-designed combinatorial plasma steroid profiles may facilitate both screening for primary aldosteronism and identification of patients with unilateral adenomas due to pathogenic KCNJ5 variants, who are most likely to show benefit from surgical intervention.