Search Results (36)

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

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

Over the last few decades, due to improvement in imaging techniques, the increased detection of adrenal incidentalomas is observed. Non-aldosterone producing adrenal adenomas (NAPACAs) often co-exist with second benign or malignant lesions. In the present study, we aimed to assess the presence of second neoplasms, both benign and malignant, in patients with NAPACAs, and to investigate possible correlations with clinical parameters, hormonal characteristics and the emergence of comorbidities. A total of 130 NAPACA patients were included in this single-center retrospective study. In this cohort, 35.4% of NAPACA patients carried any second neoplasm (either benign or malignant) whereas, 26.9% had a second malignant neoplasm. Cortisol levels after 1 mg overnight dexamethasone suppression test (F-ODS) were significantly higher in patients without a second neoplasm (p = 0.02), and this finding was consistent even when categorizing patients with and without malignancies (p = 0.02). In line with this observation, ACTH/F-ODS levels were significantly higher in patients with second malignancies (p < 0.05). Interestingly, the presence of mild autonomous cortisol secretion tended to be lower in patients with second malignancies (p = 0.08). No remarkable differences in the comorbidities of NAPACA patients with and without a second neoplasm were documented. Further prospective studies will be needed to elucidate the role of mild hypercortisolemia on the development of these second tumors in NAPACA patients. Full article

Hypertension is a critical health concern as it affects millions of people worldwide and leads to increased risk factors for other diseases such as cardiovascular diseases and stroke. Hypertension is commonly categorized into primary hypertension and secondary hypertension, with the latter frequently curable when caused by the presence of a benign adrenal adenoma that produces excessive adrenal hormones. The incidence rate of these adrenal adenomas is relatively high, in keeping with the hyperplastic/hypermutable characteristic of the adrenal gland. One of the most common functional adrenal adenomas are the aldosterone-producing adenomas (APAs), which develop from the adrenal cortex and, as per the name, produce excessive amounts of the adrenal hormone aldosterone, leading to hypertension. Investigations of genetic causes of these adenomas have revealed that the de novo somatic mutations that commonly cause the increase in aldosterone production mostly involve changes in intracellular concentration. Herein, we review the somatic genetic alterations that have been reported in APAs over the decade. Full article

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

To evaluate the secretory function of adrenal incidentaloma, this study explored the usefulness of a contrast-enhanced computed tomography (CECT)-based radiomics model for distinguishing aldosterone-producing adenoma (APA) from non-functioning adrenal adenoma (NAA). Overall, 68 APA and 60 NAA patients were randomly assigned (8:2 ratio) to either a training or a test cohort. In the training cohort, univariate and least absolute shrinkage and selection operator regression analyses were conducted to select the significant features. A logistic regression machine learning (ML) model was then constructed based on the radiomics score and clinical features. Model effectiveness was evaluated according to the receiver operating characteristic, accuracy, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis. In the test cohort, the area under the curve (AUC) of the Radscore model was 0.869 [95% confidence interval (CI), 0.734–1.000], and the accuracy, sensitivity, specificity, and F1 score were 0.731, 1.000, 0.583, and 0.900, respectively. The Clinic–Radscore model had an AUC of 0.994 [95% CI, 0.978–1.000], and the accuracy, sensitivity, specificity, and F1 score values were 0.962, 0.929, 1.000, and 0.931, respectively. In conclusion, the CECT-based radiomics and clinical radiomics ML model exhibited good diagnostic efficacy in differentiating APAs from NAAs; this non-invasive, cost-effective, and efficient method is important for the management of adrenal incidentaloma. Full article

In endocrinology, endoscopic ultrasound (EUS) may be used to image the adrenals, the endocrine pancreas, and other organs where endocrine neoplasms may occur. During the recent decades, EUS has been established predominantly to assess multiple endocrine neoplasia type 1, to localize insulinomas, and to identify aldosterone-producing adenomas. EUS in endocrinology requires special skills and individual experience in order to provide reliable diagnostic information. Full article

Aldosterone and cortisol serve important roles in the pathogenesis of cardiovascular diseases and metabolic disorders. Epigenetics is a mechanism to control enzyme expression by genes without changing the gene sequence. Steroid hormone synthase gene expression is regulated by transcription factors specific to each gene, and methylation has been reported to be involved in steroid hormone production and disease. Angiotensin II or potassium regulates the aldosterone synthase gene, CYP11B2. The adrenocorticotropic hormone controls the 11b-hydroxylase, CYP11B1. DNA methylation negatively controls the CYP11B2 and CYP11B1 expression and dynamically changes the expression responsive to continuous stimulation of the promoter gene. Hypomethylation status of the CYP11B2 promoter region is seen in aldosterone-producing adenomas. Methylation of recognition sites of transcription factors, including cyclic AMP responsive element binding protein 1 or nerve growth factor-induced clone B, diminish their DNA-binding activity. A methyl-CpG-binding protein 2 cooperates directly with the methylated CpG dinucleotides of CYP11B2. A low-salt diet, treatment with angiotensin II, and potassium increase the CYP11B2 mRNA levels and induce DNA hypomethylation in the adrenal gland. A close association between a low DNA methylation ratio and an increased CYP11B1 expression is seen in Cushing’s adenoma and aldosterone-producing adenoma with autonomous cortisol secretion. Epigenetic control of CYP11B2 or CYP11B1 plays an important role in autonomic aldosterone or cortisol synthesis. Full article

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

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

Aldosterone-producing adenomas (APAs) have different steroid profiles in serum, depending on the causative genetic mutation. Ion mobility is a separation technique for gas-phase ions based on their m/z values, shapes, and sizes. Human serum (100 µL) was purified by liquid–liquid extraction using tert-butyl methyl ether/ethyl acetate at 1/1 (v/v) and mixed with deuterium-labeled steroids as the internal standard. The separated supernatant was dried, re-dissolved in water containing 20% methanol, and injected into a liquid chromatography–ion mobility–mass spectrometer (LC/IM/MS). We established a highly sensitive assay system by separating 20 steroids based on their retention time, m/z value, and drift time. Twenty steroids were measured in the serum of patients with primary aldosteronism, essential hypertension, and healthy subjects and were clearly classified using principal component analysis. This method was also able to detect phosphatidylcholine and phosphatidylethanolamine, which were not targeted. LC/IM/MS has a high selectivity for known compounds and has the potential to provide information on unknown compounds. This analytical method has the potential to elucidate the pathogenesis of APA and identify unknown steroids that could serve as biomarkers for APA with different genetic mutations. Full article

In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the suppressive effects of MRAs on the activities of hormone synthase. The probable factors of cytochrome P-450 reduction, both in microsomes and mitochondria, have also been considered: (1) one of the spironolactone metabolite forms had destructive function, except canrenone, (2) 7α-thio-spironolactone was an obligatory intermediate in the spironolactone-induced CYP450 decrease, and (3) the contributing steroids should have 7α-methylthio or 7α-methylsulfone groups. In previous clinical research, spironolactone-body-containing cells showed a type II pattern of enzyme activity (i.e., enhanced 3β-hydroxysteroid dehydrogenase, glucose-6-phosphate, and NADP-isocitrate dehydrogenase activities and weaken succinate dehydrogenase activity), and the subcapsular micronodules composed of spironolactone-body-containing cells also exhibited a type II pattern and excess aldosterone secretion, indicating that the subcapsular micronodules might be the root of aldosterone-producing adenoma. Moreover, combined with the potential impeditive function to aldosterone secretion, a few cases of spontaneous remission of primary aldosteronism, with normal ranges of blood pressure, plasma potassium, plasma renin activity, and aldosterone renin ratio, have been reported after long-term treatment with MRAs. Full article

Primary aldosteronism (PA) is the most frequent form of secondary endocrine hypertension, which is characterized by excessive aldosterone secretion and suppressed renin. The currently recommended diagnostic algorithm is very clear, and the plasma aldosterone-to-renin ratio (ARR) is considered the first-line screening test. However, this indicator is influenced by many factors, some of which may cause false-negative results, consequently leading to underdiagnosed PA. Here, we report the rare case of a 38-year-old man who presented with bilateral accessory renal arteries and aldosterone-producing adenoma but had a negative ARR test result. Full article

Hypertension due to primary aldosteronism poses a risk of severe cardiovascular complications compared to essential hypertension. The discovery of the KCNJ5 somatic mutation in aldosteroene producing adenoma (APA) in 2011 and the development of specific CYP11B2 antibodies in 2012 have greatly advanced our understanding of the pathophysiology of primary aldosteronism. In particular, the presence of CYP11B2-positive aldosterone-producing micronodules (APMs) in the adrenal glands of normotensive individuals and the presence of renin-independent aldosterone excess in normotensive subjects demonstrated the continuum of the pathogenesis of PA. Furthermore, among the aldosterone driver mutations which incur excessive aldosterone secretion, KCNJ5 was a major somatic mutation in APA, while CACNA1D is a leading somatic mutation in APMs and idiopathic hyperaldosteronism (IHA), suggesting a distinctive pathogenesis between APA and IHA. Although the functional detail of APMs has not been still uncovered, its impact on the pathogenesis of PA is gradually being revealed. In this review, we summarize the integrated findings regarding APA, APM or diffuse hyperplasia defined by novel CYP11B2, and aldosterone driver mutations. Following this, we discuss the clinical implications of KCNJ5 mutations to support better cardiovascular outcomes of primary aldosteronism. Full article

Purpose: Adrenal venous sampling (AVS) performed to distinguish unilateral and bilateral primary aldosteronism (PA) is invasive and poorly standardized. This study aimed to identify non-invasive characteristics that can select the patients with unilateral PA who could bypass AVS before surgery. Methods: A single-center study collected a total of 450 patients with PA. Development and validation cohorts included 242 and 208 patients. The AVS was successful in 150 and 138 patients from the cohorts, and the unilateral PA was found in 96 and 94 patients, respectively. Clinical factors independently associated with lateralized AVS in multivariable logistic regression were used to construct a unilateral PA prediction score (SCORE). Results: The proposed SCORE was calculated as a sum of the prevalence of adrenal nodule on computed tomography (2 points) and plasma/serum aldosterone concentration ≥ 165 ng/L after the saline infusion test (SIT) (1 point). Importantly, the SCORE = 3 points identified 48% of unilateral PA patients with a specificity of 100% in the development cohort. The zero rate of false-positive classifications was preserved with the same cut-off value in the validation cohort. Conclusions: AVS could be omitted before surgery in patients with typical Conn´s adenoma provided the aldosterone concentration ≥ 165 ng/L after the SIT. Full article