The Primary Aldosteronism Foundation maintains a list of salient publications. Topics range from pathogenesis to the implications of excess aldosterone. We regularly update the list with new topics, and new articles are added as they become public.

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Posterior reversible encephalopathy syndrome (PRES) is an uncommon manifestation of severe hypertension. PRES most commonly manifests with headache, confusion, and vision loss, and typically, these symptoms are reversible. We present a case of a patient with chronic poorly controlled hypertension in whom PRES was the initial presentation that prompted evaluation for secondary hypertension due to primary hyperaldosteronism (i.e., Conn syndrome). The patient had a right homonymous hemianopsia due to ischemic infarct after PRES. To the best of our knowledge, this is the first case of homonymous hemianopsia as a primary manifestation of Conn syndrome to be reported in the English language ophthalmic literature.

Authors: Amir Ali, Subahari Raviskanthan, Peter W. Mortensen, Andrew G. Lee
Keywords: posterior reversible encephalopathy syndrome
DOI Number: doi: 10.1097/WNO.0000000000001351
Publication Year: 2021


Diagnosis of primary aldosteronism (PA) for many patients depends on positive results for the saline infusion test (SIT). Plasma aldosterone is often measured by immunoassays, which can return inaccurate results. The objective of this study was to establish whether differences in aldosterone measurements by immunoassay versus mass spectrometry (MS) might impact confirmatory testing for PA. This study, involving 240 patients tested using the SIT at five tertiary-care centers, assessed discordance between immunoassay and MS-based measurements of plasma aldosterone. Plasma aldosterone measured by Liaison and iSYS immunoassays were respectively 86% and 58% higher than by MS. With an immunoassay-based SIT cut-off for aldosterone of 170 pmol/L, 78 and 162 patients had respective negative and positive results. All former patients had MS-based measurements of aldosterone <117 pmol/L, below MS-based cutoffs of 162 pmol/L. Among the 162 patients with pathogenic SIT results, MS returned non-pathologic results in 62, including 32 under 117 pmol/L. Repeat measurements by an independent MS method confirmed non-pathogenic results in 53 patients with discordant results. Patients with discordant results showed a higher (P<0.0001) prevalence of non-lateralized than lateralized adrenal aldosterone production than patients with concordant results (83%vs28%). Among patients with non-lateralized aldosterone production, 66% had discordant results. Discordance was more prevalent for the Liaison than iSYS immunoassay (32%vs16% P=0.0065) and was eliminated by plasma purification to remove interferents. These findings raise concerns about the validity of immunoassay-based diagnosis of PA in over 60% of patients with presumed bilateral disease. We provide a simple solution to minimize immunoassay inaccuracy-associated misdiagnosis of PA.

Authors: Graeme Eisenhofer, Max Kurlbaum, Mirko Peitzsch, Georgiana Constantinescu, Hanna Remde, Manuel Schulze, Denise Kaden, Lisa Marie Müller, Carmina T Fuss, Sonja Kunz, Sylwia Kołodziejczyk-Kruk, Sven Gruber, Aleksander Prejbisz, Felix Beuschlein, Tracy Ann Williams, Martin Reincke, Jacques W M Lenders, Martin Bidlingmaier
Keywords: saline infusion test, immunoassay, confirmatory testing
DOI Number: 10.1210/clinem/dgab924
Publication Year: 2021


Primary aldosteronism (PA) is a common form of secondary hypertension. Adrenal venous sampling (AVS) is the gold standard for subtyping PA. This study aimed to determine whether there is a difference between immunoassays and liquid chromatography-mass spectrometry (LC-MS/MS) methods for measuring cortisol levels that affect the judgement of AVS. The study included 72 patients who were diagnosed with PA and had undergone AVS. Patients were grouped according to whether they received adrenocorticotropic hormone (ACTH) stimulation during AVS, and the cortisol results were measured using immunoassay and LC-MS/MS. There were 48 patients in the without ACTH stimulation group and 24 in the post-ACTH stimulation group during AVS (bilateral adrenal vein cannulation success rate, 56.25% vs. 83.33%). ACTH stimulation was beneficial for increasing the success rate of AVS (p < .001). Immunoassays were linearly correlated with LC-MS/MS when cortisol concentrations were <1750 nmol/L (r = .959, p < .001). When cortisol concentrations were >17,500 nmol/L, no correlation was found between the two methods (p = .093). The two methods were consistent for the detection of cortisol for evaluating the success of cannulation for AVS. Five percent of patients showed discordant lateralization of aldosterone production according to the cortisol LC-MS/MS and immunoassay results in the without ACTH group, and 15% showed discordant lateralization in the post-ACTH group. The immunoassay method can be used to determine whether cannulation is successful. The final decision for lateralization may be more appropriate based on LC-MS/MS results.

Authors: Ying Ma, Hong Chen, Fangjun Chen, Jingjing Jiang, Wei Guo, Xiaoying Li, Xin Gao, Zhiqiang Lu, Bo Zhou, Lin Zhao, Xiaomu Li
Keywords: immunoassay, liquid chromatography-mass spectrometry, cortisol
DOI Number: 10.1111/cen.14666
Publication Year: 2021


Primary aldosteronism (PA) is characterized by autonomous aldosterone production by renin-independent mechanisms and is most commonly sporadic. While 60–70% of sporadic PA can be attributed to bilateral hyperaldosteronism, the remaining 30–40% is caused by a unilateral aldosterone-producing adenoma (APA). Somatic mutations in or near the selectivity filter the KCNJ5 gene (encoding the potassium channel GIRK4) have been implicated in the pathogenesis of both sporadic and familial PA. Several studies using tumor tissue, peripheral and adrenal vein samples from PA patients have demonstrated that along with aldosterone, the hybrid steroids 18-hydroxycortisol (18OHF) and 18-oxocortisol (18oxoF) are a hallmark of APA harboring KCNJ5 mutations. Herein, we review the recent advances with respect to the molecular mechanisms underlying the pathogenesis of PA and the steroidogenic fingerprints of KCNJ5 mutations. In addition, we present an outlook toward the future of PA subtyping and diagnostic work-up utilizing steroid profiling.

Authors: Juilee Rege, Adina F. Turcu, William E. Rainey
Keywords: KCNJ5, CYP11B2, CYP17A1, 18-hydroxycortisol, 18-oxocortisol
DOI Number: 10.21037/gs.2019.10.22
Publication Year: 2020


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.

Authors: Hiroshi Akasaka, Koichi Yamamoto, Hiromi Rakugi, Motonori Nagasawa, Ryo Nakamaru, Takamasa Ichijo, Yoshiyu Takeda, Isao Kurihara, Takuyuki Katabami, Mika Tsuiki, Norio Wada, Yoshihiro Ogawa, Junji Kawashima, Masakatsu Sone, Kohei Kamemura, Takanobu Yoshimoto, Yuichi Matsuda, Megumi Fujita, Hiroki Kobayashi, Minemori Watanabe, Kouichi Tamura, Shintaro Okamura, Shozo Miyauchi, Shoichiro Izawa, Yoshiro Chiba, Akiyo Tanabe, Mitsuhide Naruse; Japan Primary Aldosteronism Study Group
Keywords: sex difference, age difference, subtype
DOI Number: 10.1161/HYPERTENSIONAHA.119.13006
Publication Year: 2019


Primary aldosteronism is increasingly investigated in hypertension being associated with an elevated cardiovascular risk. Aldosterone has been reported to increase in the luteal phase in normal women but to our knowledge the influence of the ovarian cycle on the first screening for primary aldosteronism (that is, on the levels of plasma aldosterone and its relationship to PRA levels) was never investigated. We measured hormonal levels during one cycle in 26 low-renin mild hypertensive outpatients. LH, FSH, 17 β-estradiol, progesterone, aldosterone and PRA were assayed at the seventh, fourteenth, twenty-first and twenty-eighth days of the cycle after 30 min of recumbency. Aldosterone and PRA increased from the seventh (follicular phase) to twenty-first day (luteal phase) from 11.2 to 17.8 ng 100 ml−1 and from 0.23 to 0.35 ng ml−1 h−1, respectively (both P=0.004). The proportion of patients with aldosterone >15 ng 100 ml−1 significantly increased from the follicular to the luteal phase, (8/26 vs 19/25, P=0.018); a similar increase was found for Aldosterone-PRA Ratio >30 combined with either a minimum PRA value of 0.5 ng ml−1 h−1 or aldosterone >15 ng 100 ml−1 (7/26 vs 16/25 and 7/26 vs 17/25 respectively, P<0.05). Aldosterone was positively related to PRA and progesterone. Higher aldosterone levels may be frequently encountered in the second part of the ovarian cycle in low-renin hypertensive women. This variability appears to be an important factor to be taken into account in the first-step laboratory screening for primary aldosteronism and should be considered in the process of standardization of the diagnostic work-up for this disease.

Authors: E Fommei, S Ghione, A Ripoli, S Maffei, P Di Cecco, A Iervasi, S Turchi
Keywords: ovarian cycle, luteal phase
DOI Number: 10.1038/jhh.2008.109
Publication Year: 2008

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