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Keywords = unilateral primary aldosteronism

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20 pages, 665 KB  
Review
Primary Hyperaldosteronism: Epidemiology, Diagnosis, and Clinical Associations
by Christos Savvidis, Charalampos Milionis, Argyro Pachi, Athanasios Tselebis and Ioannis Ilias
Epidemiologia 2026, 7(2), 32; https://doi.org/10.3390/epidemiologia7020032 - 2 Mar 2026
Viewed by 2747
Abstract
Background/Objectives: Primary aldosteronism (PA), the leading cause of secondary hypertension, results from autonomous aldosterone hypersecretion. It is characterized by increased extracellular volume, elevated cardiac output, and greater arterial stiffness compared with essential hypertension, reflecting aldosterone-mediated hemodynamic dysregulation. The prevalence and morbidity of PA [...] Read more.
Background/Objectives: Primary aldosteronism (PA), the leading cause of secondary hypertension, results from autonomous aldosterone hypersecretion. It is characterized by increased extracellular volume, elevated cardiac output, and greater arterial stiffness compared with essential hypertension, reflecting aldosterone-mediated hemodynamic dysregulation. The prevalence and morbidity of PA are increasingly acknowledged; however, PA continues to be underdiagnosed because of limited screening and diagnostic complexity. Methods: A narrative review was conducted using PubMed (2015–2025), with terms targeting PA epidemiology, excluding treatment-focused studies. From 971 articles, 133 relevant studies (original research studies, reviews, meta-analyses) were included, addressing prevalence, risk factors, comorbidities, genetics, and diagnostic issues. Results: PA prevalence in hypertensive populations is 5–10%, rising to 17.8% in young-onset and 20–30% in resistant hypertension. Screening indications include resistant/severe hypertension, hypokalemia, adrenal incidentaloma, young-onset disease, obstructive sleep apnea (59.8% comorbidity in hypertensive PA), and familial history, while a link may exist with papillary thyroid cancer. The aldosterone–renin ratio (ARR) is the primary screening tool, limited by assay variability and confounders (e.g., sodium intake). Confirmatory testing (such as with the saline infusion test) is often challenging to perform in routine practice. Adrenal venous sampling (AVS) is useful for subtyping unilateral (aldosterone-producing adenoma; APA; ~35–50%) vs. bilateral (idiopathic hyperaldosteronism; IHA) disease, despite technical challenges. Somatic mutations (e.g., KCNJ5, more frequent in Asians) and rare familial forms drive PA. Complications include cardiovascular events (Major Adverse Cardiovascular Events; MACE: 13.6% at 5.8 years), stroke, renal impairment (decreased eGFR, proteinuria), metabolic disorders (diabetes, obesity), and novel associations (vertebral fractures, renal stones, normal-tension glaucoma). Psychiatric comorbidities (depression/anxiety in 30–70% of patients) have been associated with central mineralocorticoid receptor effects, with sleep disturbances being prominent in females. Subclinical PA predicts hypertension and arterial stiffness. Conclusion: Improved screening protocols, standardized ARR cutoffs, and advanced imaging and genetic analyses are needed to enhance PA detection. Future research should validate cost-effective screening and clarify psychiatric-metabolic links for optimized management. Full article
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10 pages, 979 KB  
Article
Adrenalectomy as a Treatment Option for Primary Aldosteronism in the Era of Robotic-Assisted Surgeries—Is It Time to Use It More Often?
by Orit Raz, Naomi Nakash Niddam, Fahed Atamna, Alla Simonovsky, Sergey Litvin, Mia Leonov Polak, Adi Leiba and Dor Golomb
J. Clin. Med. 2026, 15(1), 173; https://doi.org/10.3390/jcm15010173 - 25 Dec 2025
Viewed by 756
Abstract
Objectives: To evaluate clinical and biochemical outcomes of robotic-assisted laparoscopic adrenalectomy in patients with primary aldosteronism (PA) due to small aldosterone-producing adenomas, with emphasis on blood pressure (BP) control, antihypertensive medication burden, hormonal normalization, and safety. Methods: We prospectively enrolled PA patients (aldosterone [...] Read more.
Objectives: To evaluate clinical and biochemical outcomes of robotic-assisted laparoscopic adrenalectomy in patients with primary aldosteronism (PA) due to small aldosterone-producing adenomas, with emphasis on blood pressure (BP) control, antihypertensive medication burden, hormonal normalization, and safety. Methods: We prospectively enrolled PA patients (aldosterone >10 ng/dL, renin <2 μU/mL) undergoing robotic adrenalectomy by a single surgeon. Exclusions included suspected pheochromocytoma, other adrenal pathologies, or malignancy. Outcomes were classified per PASO criteria at 6 months: complete success (BP <140/90 mmHg without medications + normalized aldosterone (<10 ng/dL) and renin (>2 μU/mL)), partial success (improvement in BP control with reduced medication and/or partial biochemical improvement), and failure (persistent hypertension and abnormal hormone levels). Results: From 2019 to present, 18 patients (median age 53 years; 13 male) with a median adenoma size of 15 mm (IQR 10–19.8) underwent robotic adrenalectomy (12 left, 6 right). Three (16.7%) with bilateral imaging findings had adrenal vein sampling to confirm unilateral disease. At 6 months, complete clinical success was achieved in 10 (55.5%) patients, partial success in 7 (38.9%), and failure in 1 (5.6%). Biochemically, 12 achieved complete normalization, 3 achieved partial improvement, and 3 did not complete testing. Median operative time was 110 min (IQR 100–120); median hospital stay was 3 days (IQR 3–4). No intra- or postoperative complications, transfusions, infections, or readmissions occurred. Conclusions: Robotic adrenalectomy for small aldosterone-producing adenomas in PA is safe, with high rates of BP normalization and hormonal remission and significantly reduced antihypertensive medication burden. Full article
(This article belongs to the Special Issue Clinical Advances in Minimally Invasive Urologic Surgery)
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15 pages, 774 KB  
Article
Exploring the Plasma Fatty Acid Signature of Primary Aldosteronism: Comparison with Essential Hypertension and Longitudinal Therapy Effects
by Gabriele Mango, Annalisa Castagna, Patrizia Pattini, Sergio De Marchi, Carlotta Spillere, Khulah Sadia, Francesca Begali, Sara Moruzzi, Nicola Martinelli, Luigi Marzano, Simonetta Friso and Francesca Pizzolo
Diagnostics 2025, 15(19), 2465; https://doi.org/10.3390/diagnostics15192465 - 26 Sep 2025
Viewed by 1051
Abstract
Background/Objectives: Fatty acids (FAs) play crucial roles in human physiology, and their levels have been associated with hypertension, although with inconsistent findings. Primary Aldosteronism (PA), a common, often underdiagnosed form of secondary hypertension, carries a higher risk of organ damage compared to [...] Read more.
Background/Objectives: Fatty acids (FAs) play crucial roles in human physiology, and their levels have been associated with hypertension, although with inconsistent findings. Primary Aldosteronism (PA), a common, often underdiagnosed form of secondary hypertension, carries a higher risk of organ damage compared to essential hypertension (EH). This study aimed to compare plasma FA profiles of patients with unilateral PA and EH and explore the impact of therapies. Methods: Participants were recruited at the Hypertension Unit of Verona University Hospital. PA diagnosis/subtype was confirmed according to guidelines. Blood samples were collected at enrollment and at follow-up (after treatment with a mineralocorticoid receptor antagonist (MRA) and adrenalectomy). Plasma long- and very-long-chain FAs were extracted and analyzed using gas chromatography. Results: Each sample was assessed for a panel of 19 selected FA species. Compared to EH (n = 60), PA patients (n = 22) exhibited lower plasma levels of behenic acid (p = 0.03), total monounsaturated fatty acids (p = 0.02), specifically palmitoleic (p = 0.005) and erucic acids (p = 0.02), and higher levels of ω6 polyunsaturated fatty acids (PUFAs, p = 0.02). Longitudinal analysis in PA patients showed that MRAs decreased total saturated FAs (pADJ = 0.01) and increased total PUFAs (pADJ = 0.006), and these changes were largely maintained even after adrenalectomy. Conclusions: This pilot study reveals significant alterations in the plasma FA profiles of PA patients compared to EH, suggesting a more prominent inflammatory state in PA. Both pharmacological and surgical interventions induced a positive shift in the FA profile of PA patients. These findings highlight the potential of FAs as biomarkers for PA risk stratification and may offer novel therapeutic opportunities. Full article
(This article belongs to the Special Issue Hypertension: Diagnosis and Management)
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24 pages, 603 KB  
Review
Dexamethasone Suppression Testing in Patients with Adrenal Incidentalomas with/Without Mild Autonomous Cortisol Secretion: Spectrum of Cortisol Cutoffs and Additional Assays (An Updated Analysis)
by Alexandra-Ioana Trandafir and Mara Carsote
Biomedicines 2025, 13(9), 2169; https://doi.org/10.3390/biomedicines13092169 - 5 Sep 2025
Cited by 3 | Viewed by 5248
Abstract
Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: [...] Read more.
Background/Objective: The overnight 1-mg dexamethasone suppression test (DST) represents the conventional/standard tool for endogenous hypercortisolemia screening, typically in relationship with adrenal and pituitary masses. Nevertheless, an associated spectrum of challenges and pitfalls is found in daily practice. This analysis aimed to evaluate: (I.) the diagnosis relevance of 1-mg DST in patients with adrenal incidentalomas (AIs) with/without mild autonomous cortisol secretion (MACS) exploring different cutoffs of the second-day plasma cortisol after dexamethasone administration (cs-DST) with respect to cardio-metabolic outcomes; (II.) the potential utility of adding other biomarkers to DST [plasma morning adrenocorticotropic hormone (ACTH), 24-h urinary free cortisol (UFC), late-night salivary cortisol (LNSC), dehydroepiandrosterone sulfate (DHEAS)]; and (III.) DST variability in time. Methods: This narrative analysis was based on searching full-text, English articles in PubMed (between January 2023 and April 2025) via using different term combinations: “dexamethasone suppression test” (n = 239), “diagnosis test for autonomous cortisol secretion” (n = 22), “diagnosis test for mild autonomous cortisol secretion” (n = 13) and “diagnosis test for Cushing Syndrome” (n = 61). We manually checked the title and abstract and finally included only the studies that provided hormonal testing results in adults with non-functional adenomas (NFAs) ± MACS. We excluded: reviews, meta-analyses, editorials, conference abstracts, case reports, and case series; non-human research; studies that did not provide clear criteria for distinguishing between Cushing syndrome and MACS; primary aldosteronism. Results: The sample-focused analysis (n = 13 studies) involved various designs: cross-sectional (n = 4), prospective (n = 1), retrospective (n = 7), and cohort (n = 1); a total of 4203 patients (female-to-male ratio = 1.45), mean age of 59.92 years. I. Cs-DST cutoffs varied among the studies (n = 6), specifically, 0.87, 0.9, 1.2, and 1.4 µg/dL in relationship with the cardio-metabolic outcomes. After adjusting for age (n = 1), only the prevalence of cardiovascular disease remained significantly higher in >0.9 µg/dL vs. ≤0.9 group (OR = 2.23). Multivariate analysis (n = 1) found cs-DST between 1.2 and 1.79 µg/dL was independently associated with hypertension (OR = 1.55, 95%CI: 1.08–2.23, p = 0.018), diabetes (OR = 1.60, 95%CI: 1.01–2.57, p = 0.045), and their combination (OR = 1.96, 95%CI:1.12–3.41, p = 0.018) after adjusting for age, gender, obesity, and dyslipidemia. A higher cs-DST was associated with a lower estimated glomerular filtration rate (eGFR), independently of traditional cardiovascular risk factors. Post-adrenalectomy eGFR improvement was more pronounced in younger individuals, those with lower eGFR before surgery, and with a longer post-operative follow-up. Cs-DST (n = 1) was strongly associated with AIs size and weakly associated with age, body mass index and eGFR. Cortisol level increased by 9% (95% CI: 6–11%) for each 10 mL/min/1.73 m2 decrease in eGFR. A lower cs-DST was associated with a faster post-adrenalectomy function recovery; the co-diagnosis of diabetes reduced the likelihood of this recovery (OR = 24.55, p = 0.036). II. Additional biomarkers assays (n = 5) showed effectiveness only for lower DHEAS to pinpoint MACS amid AIs (n = 2, cutoffs of <49.31 µg/dL, respectively, <75 µg/dL), and lower ACTH (n = 1, <12.6 pmol/L). III. Longitudinal analysis of DST’s results (n = 3): 22% of NFAS switch to MACS after a median of 35.7 months (n = 1), respectively, 29% (n = 1) after 48.6 ± 12.5 months, 11.8% (n = 1) after 40.4 ± 51.17 months. A multifactorial model of prediction showed the lowest risk of switch (2.4%) in individuals < 50 years with unilateral tumor and cs-DST < 0.45 µg/dL. In the subgroup of subjects without cardio-metabolic comorbidities at presentation, 25.6% developed ≥1 comorbidities during surveillance. Conclusions: The importance of exploring the domain of AIs/NFAs/MACS relates to an increasing detection in aging population, hence, the importance of their optimum hormonal characterization and identifying/forestalling cardio-metabolic consequences. The spectrum of additional biomarkers in MACS (other than DST) remains heterogeneous and still controversial, noting the importance of their cost-effectiveness, and availability in daily practice. Cs-DST serves as an independent predictor of cardio-metabolic outcomes, kidney dysfunction, while adrenalectomy may correct them in both MACS and NFAs, especially in younger population. Moreover, it serves as a predictor of switching the NFA into MACS category during surveillance. Changing the hormonal behavior over time implies awareness, since it increases the overall disease burden. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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11 pages, 1982 KB  
Article
Adrenal Vein Sampling: The Role of a Diagnostic Inspiratory Contrast-Enhanced CT Scan in Interventional Planning
by Filip Njavro, Erin Kos, Karin Zibar Tomšić, Maja Prutki and Ana Marija Alduk
Diagnostics 2025, 15(13), 1716; https://doi.org/10.3390/diagnostics15131716 - 5 Jul 2025
Viewed by 1261
Abstract
Background/Objectives: Adrenal vein sampling is the gold standard for differentiating between unilateral and bilateral primary aldosteronism and guiding treatment. This study evaluates the utility of inspiratory CT scans in interventional planning, specifically assessing the right adrenal vein visualization and positional discrepancies during [...] Read more.
Background/Objectives: Adrenal vein sampling is the gold standard for differentiating between unilateral and bilateral primary aldosteronism and guiding treatment. This study evaluates the utility of inspiratory CT scans in interventional planning, specifically assessing the right adrenal vein visualization and positional discrepancies during fluoroscopy. Methods: A retrospective analysis of 133 patients who underwent adrenal vein sampling was performed. Pre-procedural inspiratory CT scans were reviewed for visualization and location of the right adrenal vein using vertebral body levels as reference. The position of the right adrenal vein was then compared with the fluoroscopic findings during adrenal veins sampling. Results: The right adrenal vein was visualized on CT scans in 99.2% of patients. Cohen’s kappa demonstrated almost perfect agreement for both visualization of the right adrenal vein and position measurement. A median difference of three vertebral levels was observed between the level of the right adrenal vein on CT and fluoroscopy, with fluoroscopy showing a more cranial position in 91.7% of cases. Conclusions: Inspiratory CT scans visualize the right adrenal vein effectively and aid the planning of adrenal vein sampling. Understanding the positional discrepancies caused by respiratory motion is crucial for successful cannulation of the right adrenal vein, minimizing procedure time and contrast consumption and ultimately enhancing patient outcomes in the management of primary aldosteronism. Full article
(This article belongs to the Special Issue Abdominal Diseases: Diagnosis, Treatment and Management)
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14 pages, 786 KB  
Article
Occurrence of Metabolic Disorders in Bilateral Primary Aldosteronism Compared to Unilateral Primary Aldosteronism
by Chiara Grasselli, Maicol Baldini, Lucia Salvi, Grazia Vestita, Maurizio Zizzo, Davide Felaco, Maria Carolina Balli, Giulia Besutti, Aurelio Negro and Angelo Ghirarduzzi
Diseases 2025, 13(2), 52; https://doi.org/10.3390/diseases13020052 - 10 Feb 2025
Cited by 1 | Viewed by 2200
Abstract
Background: Metabolic syndrome (MetS) is a common comorbidity associated with hypertension that occurs more often in primary aldosteronism (PA). Our work aims to investigate the prevalence of MetS and its determinants in unilateral PA and bilateral PA, as confirmed by adrenal venous sampling [...] Read more.
Background: Metabolic syndrome (MetS) is a common comorbidity associated with hypertension that occurs more often in primary aldosteronism (PA). Our work aims to investigate the prevalence of MetS and its determinants in unilateral PA and bilateral PA, as confirmed by adrenal venous sampling (AVS). Methods: This was a retrospective, cross-sectional study. We investigated metabolic indicators in 160 cases of PA, categorized by AVS—82 with unilateral PA and 78 with bilateral PA. A control group of 80 non-PA patients with essential hypertension, matched for age and sex, was also included. Results: Unilateral PA had a higher aldosterone–renin ratio and lower serum potassium levels than bilateral PA. Nevertheless, bilateral PA exhibited a higher prevalence of MetS (41% vs. 30.5%; p = 0.001), obesity, BMI, LDL hypercholesterolemia, and hypertriglyceridemia than unilateral PA. Conclusions: Bilateral PA presents a greater incidence of MetS than unilateral PA, in spite of the latter showing a higher aldosterone–renin ratio and lower serum potassium levels. The results suggest that the mechanisms underlying MetS may differ between unilateral and bilateral PA. Full article
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11 pages, 426 KB  
Article
Impact of Cortisol-Cosecretion on Adrenal Venous Sampling Results in Primary Aldosteronism: Study of 225 Cases
by Cristina Lamas, Marta Araujo-Castro, Lukas Ostermair, Erik Petersenn, Paola Parra Ramírez, Ángel Rebollo-Román, Isabel Stuefchen, Denise Bruedgam, Jorge Gabriel Ruiz-Sanchez, Theodora Michalopoulou, Carolina M. Perdomo, Felicia A. Hanzu, Christian Adolf and Martin Reincke
Biomedicines 2024, 12(11), 2430; https://doi.org/10.3390/biomedicines12112430 - 23 Oct 2024
Cited by 6 | Viewed by 2849
Abstract
Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO [...] Read more.
Background/Objectives: Mild autonomous cortisol secretion (MACS) can coexist with primary aldosteronism (PA). The purpose of our study was to evaluate whether (MACS) influences parameters analyzed during adrenal venous sampling (AVS) in patients with PA. Methods: Patients with PA from the SPAIN-ALDO Registry and the German Conn’s Registry with available 1 mg-dexamethasone suppression test (DST) and AVS were included. MACS was defined as a post-DST cortisol > 1.8 µg/dL in the absence of specific signs and symptoms of Cushing’s syndrome. Results: Two-hundred and twenty-five patients were included, 98 (43.6%) of whom had concomitant MACS. The mean age was 54 ± 10 years and 37.3% were women. AVS was performed by simultaneous catheterization of both adrenal veins and analysis of basal samples in 157 patients (69.8%), with both basal and post-ACTH samples in 15 patients (6.7%), and during continuous ACTH infusion in 53 patients (23.6%). AVS was considered technically unsuccessful in 40 cases (17.8%), suggesting unilateral secretion in 106 (47.1%) and bilateral secretion in 79 (35.1%). We did not find significant differences in the percentage of unilateral and bilateral results, cortisol, corrected aldosterone, or selectivity indices in the dominant and non-dominant veins, nor in the lateralization index or the contralateral suppression index between patients with and without MACS. They also had similar rates of surgical treatment and biochemical and clinical response. Conclusions: Although pathophysiological reasoning suggests that MACS could hinder AVS identification of unilateral forms of PA, our data suggest that such interference, if it exists, is of moderate clinical relevance. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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10 pages, 2168 KB  
Article
[131I]6ß-Iodomethyl-19-norcholesterol SPECT/CT for the Lateralization of Mineralocorticoid Overproduction in Primary Aldosteronism
by Sandor Barna, Livia Sira, Harjit Pal Bhattoa, Laszlo Toth, Zsigmond Czine, Lilla Szoboszlay, Edit B. Nagy, Zita Kepes, Ildiko Garai, Miklos Bodor, Jozsef Varga and Endre V. Nagy
Diagnostics 2024, 14(17), 1997; https://doi.org/10.3390/diagnostics14171997 - 9 Sep 2024
Viewed by 1734
Abstract
Primary: aldosteronism is a frequent cause of secondary hypertension. With access to specialized care, an increasing number of patients with aldosteronism are being identified. Primary aldosteronism is treatable by adrenal surgery if aldosterone excess originates from one of the two, and not from [...] Read more.
Primary: aldosteronism is a frequent cause of secondary hypertension. With access to specialized care, an increasing number of patients with aldosteronism are being identified. Primary aldosteronism is treatable by adrenal surgery if aldosterone excess originates from one of the two, and not from both, adrenals. Bilateral hyperplasia requires lifelong mineralocorticoid receptor antagonist treatment. Up till now, adrenal venous sampling (AVS) has been widely used to distinguish between one-sided and two-sided aldosterone overproduction and patient selection for surgery. AVS is an invasive technique, and the unsuccessful sampling of the right adrenal vein during AVS often prevents side comparison, making the AVS procedure useless. Molecular imaging using [131I]6ß-iodomethyl-19-norcholesterol with SPECT CT imaging (SPECT/CT) may be a potential alternative. Methods: In 42 consecutive patients with confirmed primary aldosteronism, molecular imaging has been performed. After dexamethasone suppression of the non-affected adrenal tissue, 37 MBq [131I]6ß-iodomethyl-19-norcholesterol was injected i.v., and SPECT/CT images were taken 7 days later. Based on the visual evaluation of the images by two nuclear medicine specialists, patients with one-sided tracer accumulation underwent adrenalectomy. To identify a SPECT/CT parameter that best characterizes the side difference, the maximum counts and the mean counts of spherical VOIs were analyzed. Results: Of the 42 patients, 24 had one-sided aldosterone overproduction by SPECT/CT. After surgical removal of the involved adrenal, all 24 patients with SPECT/CT-identified unilateral aldosteronism achieved biochemical cure, defined as a normalized potassium level combined with an aldosterone-to-renin ratio ≤ 30. To identify the best measurable parameter of SPECT/CT side difference, the mean counts and maximum counts of a series of spherical VOIs of different diameters were analyzed. The ratio of the mean counts of 3 cm spherical VOIs of the right and left adrenal regions (lateralization index) was the best discriminator; a ratio of ≥1.29 was characteristic of one-sided disease, without overlap between the one-sided and two-sided patient groups. Conclusions: [131I]6ß-iodomethyl-19-norcholesterol SPECT/CT with a count-based image interpretation and side-ratio calculation may be an equipollent non-invasive substitute for adrenal venous sampling in the lateralization of mineralocorticoid overproduction. It reliably identifies unilateral disease and facilitates patients’ selection for surgical intervention. If confirmed by others, this functional imaging may replace AVS when lateralization is required for management decisions in primary aldosteronism. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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17 pages, 412 KB  
Review
What We Know about and What Is New in Primary Aldosteronism
by Natalia Ekman, Ashley B. Grossman and Dorota Dworakowska
Int. J. Mol. Sci. 2024, 25(2), 900; https://doi.org/10.3390/ijms25020900 - 11 Jan 2024
Cited by 13 | Viewed by 8918
Abstract
Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5–10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while [...] Read more.
Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5–10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism. Full article
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24 pages, 774 KB  
Review
Cross-Disciplinary Approach of Adrenal Tumors: Insights into Primary Aldosteronism-Related Mineral Metabolism Status and Osteoporotic Fracture Risk
by Alexandra-Ioana Trandafir, Ana-Maria Gheorghe, Oana-Claudia Sima, Adrian Ciuche, Eugenia Petrova, Claudiu Nistor and Mara Carsote
Int. J. Mol. Sci. 2023, 24(24), 17338; https://doi.org/10.3390/ijms242417338 - 11 Dec 2023
Cited by 7 | Viewed by 3763
Abstract
Our objective was to overview the novel aspects in the field of adrenal gland neoplasms, namely, the management of bone status with respect to primary aldosteronism (PA). In the current narrative review, a PubMed study was conducted from inception until June 2023. The [...] Read more.
Our objective was to overview the novel aspects in the field of adrenal gland neoplasms, namely, the management of bone status with respect to primary aldosteronism (PA). In the current narrative review, a PubMed study was conducted from inception until June 2023. The inclusion criteria were: human (clinically relevant) studies of any study design (at least 10 patients per study); English papers; and the following combination of key words within the title and/or abstract: “aldosterone” AND “bone”, “skeleton”, “osteoporosis”, “fracture”, “calcium”, “parathyroid”, “DXA”, “osteocalcin”, “P1NP”, “alkaline phosphatase”, “bone marker”, “trabecular bone score”, or “FRAX”. The exclusion criteria were in vitro or animal studies, reviews, and case reports/series. We screened 1027 articles and finally included 23 studies (13 of case-control type, 3 cross-sectional, 5 prospective, 1 observational cohort, and 1 retrospective study). The assessments provided in these studies were as follows: nine studies addressed Dual-Energy X-ray Absorptiometry (DXA), another study pointed out a bone microarchitecture evaluation underlying trabecular bone score (TBS), and seven studies investigated the bone turnover markers (BTMs) profile. Moreover, 14 studies followed the subjects after adrenalectomy versus medical treatment, and 21 studies addressed secondary hyperparathyroidism in PA patients. According to our study on published data during a period of almost 40 years (n = 23, N = 3965 subjects aged between 38 and 64, with a mean age 56.75, and a female-to-male ratio of 1.05), a higher PTH in PA versus controls (healthy persons or subjects with essential hypertension) is expected, secondary hyperparathyroidism being associated in almost half of the adults diagnosed with PA. Additionally, mineral metabolism anomalies in PA may include lower serum calcium and higher urinary calcium output, all these three parameters being reversible under specific therapy for PA, regardless medical or surgical. The PA subgroup with high PTH seems at higher cardiovascular risk, while unilateral rather than bilateral disease was prone to this PTH anomaly. Moreover, bone mineral density (BMD) according to central DXA might show a higher fracture risk only in certain adults, TBS being a promising alternative (with a still unknown perspective of diabetes’ influence on DXA-TBS results in PA). However, an overall increased fracture prevalence in PA is described in most studies, especially with respect to the vertebral site, the fracture risk that seems correctable upon aldosterone excess remission. These data recommend PA as a cause of secondary osteoporosis, a treatable one via PA intervention. There is still an area of debate the way to address BMTs profile in PA, the case’s selection toward specific bone evaluation in every day practice, and further on, the understanding of the potential genetic influence at the level of bone and mineral complications in PA patients. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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10 pages, 865 KB  
Communication
Diagnostic Accuracy of Adrenal Iodine-131 6-Beta-Iodomethyl-19-Norcholesterol Scintigraphy for the Subtyping of Primary Aldosteronism
by Marta Araujo-Castro, Miguel Paja Fano, Marga González Boillos, Eider Pascual-Corrales, Ana María García Cano, Paola Parra Ramírez, Patricia Martín Rojas-Marcos, Almudena Vicente Delgado, Anna Casteràs, Albert Puig, Iñigo García Sanz, Patricia Díaz Guardiola, Cristina Robles Lázaro, Miguel Antonio Sampedro Núñez, Raquel Guerrero-Vázquez, María del Castillo Tous, Theodora Michalopoulou Alevras, Susana Tenes Rodrigo and Felicia A. Hanzu
Biomedicines 2023, 11(7), 1934; https://doi.org/10.3390/biomedicines11071934 - 7 Jul 2023
Cited by 8 | Viewed by 3450
Abstract
Purpose: To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome [...] Read more.
Purpose: To evaluate the diagnostic accuracy of the 131I-6β-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy for the subtyping diagnosis of primary aldosteronism (PA), considering as gold standard for the diagnosis of unilateral PA (UPA), either the results of the adrenal venous sampling (AVS) or the outcome after adrenalectomy. Methods: A retrospective multicenter study was performed on PA patients from 14 Spanish tertiary hospitals who underwent NP-59 scintigraphy with an available subtyping diagnosis. Patients were classified as UPA if biochemical cure was achieved after adrenalectomy or/and if an AVS lateralization index > 4 with ACTH stimulation or >2 without ACTH stimulation was observed. Patients were classified as having bilateral PA (BPA) if the AVS lateralization index was ≤4 with ACTH or ≤2 without ACTH stimulation or if there was evidence of bilateral adrenal nodules >1 cm in each adrenal gland detected by CT/MRI. Results: A total of 86 patients with PA were included (70.9% (n = 61) with UPA and 29.1% (n = 25) with BPA). Based on the NP-59 scintigraphy results, 16 patients showed normal suppressed adrenal gland uptake, and in the other 70 cases, PA was considered unilateral in 49 patients (70%) and bilateral in 21 (30%). Based on 59-scintigraphy results, 10.4% of the patients with unilateral uptake had BPA, and 27.3% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the NP-59 scintigraphy for PA subtyping was 0.812 [0.707–0.916]. Based on the results of the CT/MRI and NP-59 scintigraphy, only 6.7% of the patients with unilateral uptake had BPA, and 24% of the cases with bilateral uptake had UPA. The AUC of the ROC curve of the model combining CT/MRI and 59-scintigraphy results for subtyping PA was 0.869 [0.782–0.957]. Conclusion: The results of NP-59 scintigraphy in association with the information provided by the CT/MRI may be useful for PA subtyping. However, their diagnostic accuracy is only moderate. Therefore, it should be considered a second-line diagnostic tool when AVS is not an option. Full article
(This article belongs to the Special Issue Adrenal Diseases: An Update)
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14 pages, 4416 KB  
Article
An Ancillary Method for Adrenal Venous Sampling in Cases in Which Right Adrenal Vein Sampling Is Difficult
by Akira Yamamoto, Takeshi Fukunaga, Mitsuru Takeuchi, Hiroki Nakamura, Akihiko Kanki, Atsushi Higaki and Tsutomu Tamada
Diagnostics 2023, 13(4), 649; https://doi.org/10.3390/diagnostics13040649 - 9 Feb 2023
Cited by 6 | Viewed by 2974
Abstract
Catheterization of the right adrenal vein (rt.AdV) to obtain blood samples can often be difficult. The aim of the present study was to investigate whether blood sampling from the inferior vena cava (IVC) at its juncture with the rt.AdV can be an ancillary [...] Read more.
Catheterization of the right adrenal vein (rt.AdV) to obtain blood samples can often be difficult. The aim of the present study was to investigate whether blood sampling from the inferior vena cava (IVC) at its juncture with the rt.AdV can be an ancillary to sampling of blood directly from the rt.AdV. This study included 44 patients diagnosed with primary aldosteronism (PA) in whom AVS with adrenocorticotropic hormone (ACTH) was performed, resulting in a diagnosis of idiopathic hyperaldosteronism (IHA) (n = 24), and patients diagnosed with unilateral aldosterone-producing adenoma (APA) (n = 20; rt.APA = 8, lt.APA = 12). In addition to regular blood sampling, blood was also sampled from the IVC, as the substitute rt.AdV [S-rt.AdV]. Diagnostic performance with the conventional lateralized index (LI) and the modified LI using the S-rt.AdV were compared to examine the utility of the modified LI. The modified LI of the rt.APA (0.4 ± 0.4) was significantly lower than those of the IHA (1.4 ± 0.7) (p < 0.001) and the lt.APA (3.5 ± 2.0) (p < 0.001). The modified LI of the lt.APA was significantly higher than those of the IHA (p < 0.001) and rt.APA (p < 0.001). Likelihood ratios to diagnose rt.APA and lt.APA using the modified LI with threshold values of 0.3 and 3.1 were 27.0, and 18.6, respectively. The modified LI has the potential to be an ancillary method for rt.AdV sampling in cases in which rt.AdV sampling is difficult. Obtaining the modified LI is extremely simple, which might complement conventional AVS. Full article
(This article belongs to the Special Issue Advances in Diagnostic Approaches for Integrative Medicine)
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9 pages, 514 KB  
Article
The Therapeutic Intensity Score as Predictor of Clinical Outcomes after Total and Partial Adrenalectomy for Unilateral Primary Aldosteronism: Results of a Multicentric Series
by Umberto Anceschi, Marilda Mormando, Rocco Simone Flammia, Cristian Fiori, Orazio Zappalà, Bernardino De Concilio, Aldo Brassetti, Alessandro Carrara, Maria Consiglia Ferriero, Gabriele Tuderti, Leonardo Misuraca, Francesco Prata, Antonio Tufano, Alfredo Maria Bove, Riccardo Mastroianni, Marialuisa Appetecchia, Giuseppe Tirone, Francesco Porpiglia, Antonio Celia and Giuseppe Simone
J. Clin. Med. 2023, 12(3), 997; https://doi.org/10.3390/jcm12030997 - 28 Jan 2023
Cited by 5 | Viewed by 2046
Abstract
Background: To evaluate the ability of therapeutic intensity score (TIS) in predicting the clinical outcomes of partial (PA) and total adrenalectomy (TA) for UPA. Methods: Between 2011 and 2022, a four-center adrenalectomy dataset was queried for “unilateral adrenal mass” and “UPA” (n = [...] Read more.
Background: To evaluate the ability of therapeutic intensity score (TIS) in predicting the clinical outcomes of partial (PA) and total adrenalectomy (TA) for UPA. Methods: Between 2011 and 2022, a four-center adrenalectomy dataset was queried for “unilateral adrenal mass” and “UPA” (n = 90). Preoperative TIS of each antihypertensive medication were individually calculated and merged to create a single, cumulative variable. Probability of complete clinical, partial, and absent pooled success rates according to TIS were assessed for the overall cohort by Kaplan–Meier. Cox analyses were used to identify predictors of complete clinical and partial/absent success, respectively. For all analyses, a two-sided p < 0.05 was considered significant. Results: At a median follow-up of 42 months (IQR 27–54) complete partial, and absent clinical success were observed in 60%, 17.7%, and 22.3%, respectively. On Kaplan–Meier analysis, TIS < 1 predicted higher complete success rates (p < 0.001), while TIS ≥ 1 was predictor of either partial and absent clinical success (p = 0.008). On multivariable analysis, TIS < 1 (HR 0.25; 95% CI 0.11–0.57; p = 0.001) and adenoma size (HR 1.11; 95% CI 1–1.23; p = 0.0049) were independent predictors of complete clinical success, while TIS ≥ 1 (HR 2.84; 95% CI 1.32–6.1; p = 0.007) was the only independent predictor of absent clinical success. Conclusions: TIS score and adenoma size may help to identify patients who are likely to be at risk of persistent hypertension after surgery. Full article
(This article belongs to the Special Issue Robotic Assisted Adrenalectomy: Is it Ready for Prime Time?)
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15 pages, 1570 KB  
Article
Validation of Existing Clinical Prediction Tools for Primary Aldosteronism Subtyping
by Barbora Kološová, Petr Waldauf, Dan Wichterle, Jan Kvasnička, Tomáš Zelinka, Ondřej Petrák, Zuzana Krátká, Lubomíra Forejtová, Jan Kaván, Jiří Widimský and Robert Holaj
Diagnostics 2022, 12(11), 2806; https://doi.org/10.3390/diagnostics12112806 - 15 Nov 2022
Cited by 7 | Viewed by 2656
Abstract
The new clinical prediction score (SCORE) has been recently proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). This study aimed to compare that SCORE with previously published scores and their validation using a cohort of patients at our center [...] Read more.
The new clinical prediction score (SCORE) has been recently proposed for primary aldosteronism (PA) subtyping prior to adrenal vein sampling (AVS). This study aimed to compare that SCORE with previously published scores and their validation using a cohort of patients at our center who had had positive SIT confirming PA and had been diagnosed with either bilateral PA according to AVS or unilateral PA if biochemically cured after an adrenalectomy. Final diagnoses were used to evaluate the diagnostic performance of the proposed clinical prediction tools. Only Kamemura’s model (with a maximum score of 4 points) and Kobayashi’s score (with a maximum score of 12 points) reached 100% reliability for prediction of bilateral PA; however, with sensitivity of only 3%. On the other hand, the values of SCORE = 3 (with sensitivity of 48%), the SPACE score ≥18 (with sensitivity of 35%), the Kobayashi’s score ≤2 (with sensitivity of 28%), and the Kocjan’s score = 3 (with sensitivity of 28%) were able to predict unilateral PA with 100% probability. Furthermore, Umakoshi’s and Young’s models both reached 100% reliability for a unilateral PA with score = 4 and both predictive factors together respectively; however, the sensitivity was lower compared with previous models; 4% and 14%, respectively. None of the clinical prediction tools applied to our cohort predicted unilateral and bilateral subtypes together with the expected high diagnostic performance, and therefore can only be used for precisely defined cases. Full article
(This article belongs to the Special Issue Advances in Vascular Imaging)
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14 pages, 776 KB  
Review
Imaging or Adrenal Vein Sampling Approach in Primary Aldosteronism? A Patient-Based Approach
by Irene Tizianel, Chiara Sabbadin, Caterina Mian, Carla Scaroni and Filippo Ceccato
Tomography 2022, 8(6), 2735-2748; https://doi.org/10.3390/tomography8060228 - 9 Nov 2022
Cited by 3 | Viewed by 4164
Abstract
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, associated with an increased risk of cardiovascular and cerebral disease, compared to essential hypertension. Therefore, it is mandatory to promptly recognize the disease and offer to the patient the correct diagnostic–therapeutic process [...] Read more.
Primary aldosteronism (PA) is the most frequent cause of secondary hypertension, associated with an increased risk of cardiovascular and cerebral disease, compared to essential hypertension. Therefore, it is mandatory to promptly recognize the disease and offer to the patient the correct diagnostic–therapeutic process in order to reduce new-onset cardiovascular events. It is fundamental to define subtype classification (unilateral or bilateral disease), in order to provide the best treatment (surgery for unilateral and medical treatment for bilateral disease). Here, we report five clinical cases of different subtypes of PA (patients with monolateral or bilateral PA, nondiagnostic AVS, allergy to iodinated contrast, and patients not suitable for surgery), with particular attention to the diagnostic–therapeutic process and the different approaches tailored to a single case. Since PA is a spectrum of various diseases, it needs a personalized diagnostic–therapeutic process, customized for the individual patient, depending on previous medical history, suitability for the surgery and patient’s preferences. Full article
(This article belongs to the Special Issue Tumor Diagnosis and Treatment: Imaging Assessment)
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