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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The incidence of adrenal tumors has increased 10-fold over the past 2 decades, in parallel to the growing number of computed tomography (CT) abdominal scans (1). The observed increase in the incidence of adrenal tumors was mainly due to more frequent discovery of smaller adrenal incidentalomas in older patients (1). However, because an abdominal CT scan is usually ordered to evaluate a medical concern, imaging bias is very likely in any prevalence study that relies on the availability of imaging (1–5). Another concern is underreporting of adrenal lesions noted on CT scans.

Authors: Irina Bancos
Keywords: adrenal incidentalomas, prevalence
DOI Number: 10.7326/M22-2600
Publication Year: 2022


Primary aldosteronism is the most common surgically curable cause of endocrine hypertension. Management of the unilateral subtype of primary aldosteronism with adrenalectomy requires multidisciplinary input. It is unclear if a dedicated endocrine hypertension service confers better outcomes compared to standard care offered by individual clinicians. In this retrospective study, patients from the Monash University Endocrine Surgery Database were divided into either the endocrine hypertension service group, where patients were managed by a dedicated multidisciplinary team, or the standard group, where patients were managed by individual clinicians. The comparisons included patient selection for surgery, perioperative blood pressure control, and surgical cure rate. Despite similar perioperative blood pressure, patients in the endocrine hypertension service group (n = 41) were on fewer antihypertensive medications (1 vs 2, P = .011) compared to the standard group (n = 55). A larger proportion of patients in the endocrine hypertension service group had either bilateral adrenal nodules or no adrenal lesions on computed tomography (41% vs 18%, P = .013). Patients in the standard group had larger adrenal lesions on computed tomography (median 15 mm vs 10 mm, P = .032). Postoperatively, the biochemical cure rate was higher in the endocrine hypertension service group at 6 to 12 months (97% vs 76%, P = .021). Patients managed by endocrine hypertension service were more likely to be diagnosed with surgically curable primary aldosteronism without a unilateral adrenal adenoma on imaging, required fewer medications for perioperative blood pressure control, and experienced superior postoperative outcomes. Referral to a dedicated endocrine hypertension service is recommended for patients with primary aldosteronism who wish to pursue a surgical cure.

Authors: Jinghong Zhang, Jun Yang, Renata Libianto, Jimmy Shen, Peter J.Fuller, Simon Grodski, James C. Lee
Keywords: referral, endocrine hypertension
DOI Number: 10.1016/j.surg.2022.08.010
Publication Year: 2022


Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is being reported more frequently. Several somatic mutations including PRKACAGNAS, and CTNNB1 were identified in cortisol-producing adenomas (CPAs). The presence of these mutations in unilateral PA (uPA) patients concurrent with ACS (uPA/ACS) is not well known. This study aimed to investigate the prevalence of these mutations and their clinical vs pathological characteristics in uPA/ACS. This is a retrospective cohort study. Totally 98 uPA patients from the Taiwan Primary Aldosteronism Investigation registry having overnight 1-mg dexamethasone suppression test (DST) and adrenalectomy from 2016 to 2018 were enrolled. Their adrenal tumors were tested for PRKACAGNAS, and CTNNB1 mutations. 11 patients had CPA-related mutations (7 PRKACA and 4 GNAS). The patients carrying these mutations had higher post-DST cortisol (5.6 vs 2.6 μg/dL, P = 0.003) and larger adenoma (2.2 ± 0.3 vs 1.9 ± 0.7 cm, P = 0.025). Adenomas with these mutations had a higher prevalence of non-classical uPA (72.7% vs 26.3%, P = 0.014). Numerically, slightly more complete clinical success of uPA patients with these mutations was noticed after adrenalectomy, although it was statistically non-significant. Post-DST cortisol levels, adenoma size >1.9 cm, and the interaction of adenoma size >1.9 cm with potassium level were found to be associated with the presence of these mutations. Our study showed that CPA-related mutations were detected in 36.7% of uPA/ACS adenomas. The presence of these mutations was associated with higher post-DST cortisol levels, larger adenoma sizes, and a high percentage of non-classical uPA. However, these mutations did not significantly affect the clinical and biochemical outcomes after adrenalectomy of uPA/ACS patients but they showed a better trend.

Authors: Wan-Chen Wu, Kang-Yung Peng, Jin-Ying Lu, Chieh-Kai Chan, Chih-Yuan Wang, Fen-Yu Tseng, Wei-Shiung Yang, Yen-Hung Lin, Po-Chih Lin, Ting-Chu Chen, Kuo-How Huang, Jeff S Chueh, Vin-Cent Wu
Keywords: cortisol, somatic mutation, autonomous secretion
DOI Number: 10.1530/EJE-22-0286
Publication Year: 2022


Cortisol measurements are essential for the interpretation of adrenal venous samplings (AVS) in primary aldosteronism (PA). Cortisol cosecretion may influence AVS indices. We aimed to investigate whether cortisol cosecretion affects non-ACTH stimulated AVS results. A retrospective cohort study was conducted at a tertiary referral center. We analyzed 278 PA patients who underwent non-ACTH stimulated AVS and had undergone at least a 1-mg dexamethasone suppression test (DST). Subsets underwent additional late-night salivary cortisol (LSC) and/or 24-hour urinary free cortisol (UFC) measurements. Patients were studied from 2013-2020 with follow-up data of 6 months following adrenalectomy or mineralocorticoid antagonist therapy initiation. We analyzed AVS parameters including adrenal vein aldosterone/cortisol ratios, selectivity, lateralization (LI) and contralateral suppression indices and post-operative ACTH-stimulation. We classified outcome according to PASO criteria. 18.9% had a pathological DST result (1.9-5 µg/dl: n=44 (15.8%); > 5 µg/dl: n=8 (2.9%)). Comparison of AVS results stratified according to the 1-mg DST (≤ 1.8 vs. >1.8 µg/dl: p=0.499; ≤ 1.8 vs. 1.8 ≤ 5 vs. > 5 µg/dl: p=0.811) showed no difference. Lateralized cases with post DST serum cortisol values > 5 µg/dL had lower LI (≤ 1.8 µg/dL: 11.11 [5.36; 26.76] vs. 1.9-5 µg/dL: 11.76 [4.9; 31.88] vs. > 5 µg/dL: 2.58 [1.67; 3.3]; p=0.008). PASO outcome was not different according to cortisol cosecretion. Marked cortisol cosecretion has the potential to influence non-ACTH stimulated AVS results. While this could result in falsely classified lateralized cases as bilateral, further analysis of substitutes for cortisol are required to unmask effects on clinical outcome.

Authors: Daniel Alexander Heinrich, Marcus Quinkler, Christian Adolf, Laura Handgriff, Lisa Müller, Holger Schneider, Lisa Sturm, Heike Künzel, Max Seidensticker, Sinan Deniz, Roland Ladurner, Felix Beuschlein, Martin Reincke
Keywords: cortisol, cosecretion, ACTH, stimulation, adrenal venous sampling
DOI Number: 10.1530/EJE-21-0541
Publication Year: 2022


With the widespread use of advanced imaging technology, adrenal tumors are increasingly being identified. The objective of this study was to investigate the prevalence and characteristics of adrenal tumors in an unselected screening population in China. We conducted a cross-sectional study at a health examination center in China. Adults having an annual checkup were invited to be screened for adrenal tumors by adrenal computed tomography. The participants with adrenal tumors had further evaluation for malignancy risk and adrenal function. A total of 25 356 participants were screened, 351 of whom were found to have adrenal tumors, for a prevalence of 1.4%. The prevalence increased with age, from 0.2% in participants aged 18 to 25 years to 3.2% in those older than 65 years. Among 351 participants with adrenal tumors, 337 were diagnosed with an adrenocortical adenoma, 14 with another benign nodule, and none with a malignant mass. In 212 participants with an adenoma who completed endocrine testing, 69.3% were diagnosed with a nonfunctioning adenoma, 18.9% with cortisol autonomy, 11.8% with primary aldosteronism, and none with pheochromocytoma. Proportions of nonfunctioning adenomas were similarly high in various age groups (72.2%, 67.8%, and 72.2% in those aged <46, 46 to 65, and ≥66 years, respectively). Only 212 of 337 participants with an adrenocortical adenoma had endocrine testing. The prevalence of adrenal tumors in the general adult screening population is 1.4%, and most of these tumors are nonfunctioning regardless of patient age. Cortisol and aldosterone secretion are the main causes of functional adenomas.

Authors: Ying Jing, Jinbo Hu, Rong Luo, Yun Mao, Zhixiao Luo, Mingjun Zhang, Jun Yang, Ying Song, Zhengping Feng, Zhihong Wang, Qingfeng Cheng, Linqiang Ma, Yi Yang, Li Zhong, Zhipeng Du, Yue Wang, Ting Luo, Wenwen He, Yue Sun, Fajin Lv, Qifu Li, MD, Shumin Yang
Keywords: prevalence, adrenal tumors
DOI Number: 10.7326/M22-1619
Publication Year: 2022


The objective of this study was to highlight the importance of hypokalemia correction in the diagnosis of primary aldosteronism (PA), which is not emphasized sufficiently in the literature or clinical guidelines. We report the cases of 4 patients with hypokalemia and hypertension in whom the screening and confirmatory diagnosis of PA was made possible only after potassium level normalization. Cases 1 and 2 were referred for evaluation of hypokalemia and hypertension while cases 3 and 4 were admitted to the hospital for severe generalized weakness and palpitations, respectively. Initial labs for all were remarkable for hypokalemia, with potassium levels of 1.9 to 3.2 mEq/L (normal range: 3.5 to 5.0 mEq/L), relatively low aldosterone of <1.0 to 13.0 ng/dL, and elevated aldosterone-to-renin ratio. Saline infusion tests were performed for cases 1 and 2 when potassium was 3.2 mEq/L with post-test aldosterone levels of 9.0 and 3.0 ng/dL, respectively, suggesting the diagnosis of PA as less likely. After potassium repletion, with potassium levels of 3.7 to 4.8 mEq/L, screening aldosterone levels were 27.0 to 64.0 ng/dL, the aldosterone-to-renin ratios were 34.5 to 128.0, and post-saline infusion test aldosterone levels were 27.0 to 64.0 ng/dL, confirming the diagnosis of PA. Computed tomography scans revealed unilateral adrenal adenomas, adrenal vein sampling confirmed the localization, and successful adrenalectomy was done for all 4 cases. Hypertension and hypokalemia resolved in the first 3 cases and improved in the fourth. Hypokalemia may confound the screening and confirmatory work up of PA due to false-negative results. Potassium normalization is very important for correct diagnosis of PA.

Authors: Michael Morkos, Yu-Chien Cheng, Leon Fogelfeld
Keywords: screening, diagnosis, hypokalemia, potassium normalization
DOI Number: 10.4158/ACCR-2018-0272
Publication Year: 2018