Xiaoxiao Song

Background: Primary aldosteronism (PA) is a leading cause of resistant hypertension with excess cardiovascular and renal damage. Adrenal venous sampling (AVS) is a reliable procedure for lateralizing primary aldosteronism (PA). However, the optimal preoperative supine duration before AVS remains controversial. We hypothesis that a 15-minute preoperative supine rest would yield equivalent AVS diagnostic performance for guiding PA management. Methods: This single-centre, prospective non-inferiority randomized controlled trial enrolled patients with confirmed PA at a tertiary hospital in China between March 2023 and October 2025. Eligible participants were randomly assigned to 15-minute or 2-hour pre-AVS supine rest, with at least 6 months of follow-up after treatment. We adopted modified intention-to-diagnose analysis. The primary outcome was complete biochemical remission after AVS-directed therapy; secondary outcomes included the complete clinical remission rate, antihypertensive medication dosage, systolic and diastolic blood pressure, and adverse events. This trial was registered in ClinicalTrials.gov (NCT05658705). Findings: 130 patients were screened, and 125 were randomized (15-min group n=64; 2-h group n=61). The primary non-inferiority endpoint was satisfied: complete biochemical remission was 70.3% (45/64) in the 15-minute group versus 80.3% (49/61) in the 2-hour group (p=0.14). The two groups also had comparable rates of complete clinical remission (15min: 37.5% [24/64]); 2hr: 37.7% [23/61]; p=0.84). While 15-minute rest yielded lower adrenal vein cortisol and selectivity index (SI) (right adrenal vein, p=0.001; left adrenal vein, p=0.01), the critical lateralization index (LI) was comparable between groups (p=0.90). Interpretation: Shortening preprocedural supine time to 15 minutes does not compromise AVS diagnostic accuracy to guide PA surgical or medical treatment. Although brief recumbency lowers adrenal venous cortisol and SI, lateralization capacity is preserved. A 15-minute supine protocol improves patient comfort and clinical workflow without sacrificing AVS accuracy, suitable for centres with extensive experience.

Background: Primary aldosteronism (PA) and pheochromocytoma (PHEO) are both causes of secondary hypertension. Since these two diseases have different pathogeneses, the coexistence of PA and PHEO is very rare and poses challenges in diagnosis and treatment. Case presentation: A 65-year-old woman developed paroxysmal hypertension two years ago, accompanied by palpitation, dizziness, headache, and vomiting, and she had a poor response to conventional antihypertensive drugs. Contrast-enhanced computed tomography showed a nodule in the medial limb of the right adrenal gland. A mildly elevated aldosterone to renin ratio and an unsuppressed captopril challenge test met the diagnostic criteria for primary aldosteronism. Normetanephrine was elevated in plasma catecholamine testing. Adrenal venous sampling (AVS) demonstrated bilateral aldosterone excess. Right adrenalectomy was performed after multidisciplinary discussion and resulted in rapid clinical improvement. Postoperative pathology revealed coexistence of a cortical aldosterone-producing nodule (APN), a micro-pheochromocytoma and multiple aldosterone-producing micronodules (multiple APM) in adrenal cortex. A KCNJ5 mutation was found in the APN, representing the first report of this gene mutation in APN in cases coexisting PA and PHEO. Conclusions: We report a rare case of concurrent PA and micro-pheochromocytoma. This case highlights the importance of early identification and diagnosis, and it provides experience regarding the diagnostic and treatment protocol for such a rare condition. Pathological findings and the KCNJ5 mutation in APN provide directions for subsequent research on the pathogenesis of concomitant PA and PHEO.

Background: The convergence of viral infection, autoimmune thyroid disease, and cardiovascular vulnerability may create a “triple systemic stress” predisposing to Takotsubo cardiomyopathy (TTS). We describe a case illustrating this potential pathophysiological triad. Case presentation: A previously healthy 21-year-old male presented with sinus tachycardia, anterior ST-segment elevation on preoperative Electrocardiogram (ECG), and regional wall motion abnormalities on echocardiography two weeks after SARS-CoV-2 infection. Emergency coronary angiography ruled out myocardial infarction and coronary stenosis. Clinical features suggested thyrotoxicosis, confirmed by biochemical and imaging studies. Cardiac magnetic resonance demonstrates subendocardial hypoperfusion in the interventricular septum accompanied by abnormal myocardial motion. Treatment with methimazole and beta-blockers led to resolution of cardiac dysfunction and gradual normalization of thyroid function. Conclusion: This case report describes a temporal association among SARS-CoV-2 infection, exacerbation of autoimmune thyroid dysfunction, and Takotsubo syndrome. The virus may contribute to Graves' disease exacerbation through immune-inflammatory mechanisms, while potentially inducing myocardial stress via cytokine-mediated pathways. These converging factors—combined with thyrotoxicosis-related catecholamine sensitivity—may act synergistically to increase TTS susceptibility. Clinically, thyroid evaluation may be considered in COVID-19 patients presenting with cardiac symptoms, and an integrated management approach addressing viral, endocrine, and cardiovascular aspects could be beneficial. The precise interconnections among these factors remain speculative and warrant further investigation in larger cohorts.

Rationale: Heart failure (HF) is slightly more common in primary aldosteronism (PA) than in essential hypertension, but early-onset HF remains rare. In such cases, underlying genetic cardiomyopathies should be considered. Autonomously secreted aldosterone and activation of the renin-angiotensin-aldosterone system can lead to extremely high aldosterone levels, worsening cardiac function and creating major therapeutic challenges. Patient concerns: A 39-year-old male presented with progressive chest tightness and shortness of breath for 4 months. He had a 7-year history of hypertension and persistent hypokalemia. Electrocardiogram revealed a markedly reduced left ventricular ejection fraction of 18.3%. Diagnosis and interventions: The patient was diagnosed with PA based on elevated plasma aldosterone concentration, an increased aldosterone-to-renin ratio, and a positive captopril challenge test. Computed tomography and adrenal vein sampling indicated unilateral PA. After initial HF management, the patient underwent laparoscopic adrenalectomy for PA treatment. Outcomes: According to the primary aldosteronism surgical outcome consensus criteria for postoperative evaluation of PA, complete biochemical remission (normalization of aldosterone-to-renin ratio and potassium) and partial clinical remission (stable blood pressure with reduced antihypertensive medication) were achieved 1 month postoperatively and have been maintained since. At the 8-month follow-up, his left ventricular ejection fraction had improved to 45.4% and BNP levels normalized. Whole-exon sequencing revealed a missense mutation of the dystrophin ( DMD ) gene. Certain DMD mutations are linked to X-linked dilated cardiomyopathy with absent or subclinical skeletal muscle involvement. Sanger sequencing confirmed the hemizygous mutation in the proband. The final diagnosis was poorly controlled PA with early-onset HF, potentially influenced by a coexisting DMD gene missense mutation that may modify both the onset and severity of PA-related HF. Lessons: Early recognition and surgical treatment of PA with early-onset HF can substantially improve cardiac function, even in the presence of genetic susceptibility to cardiomyopathy. This case underscores the need to consider underlying cardiac genetic disorders in PA patients with atypical or early-onset HF and raises the hypothesis that the identified DMD variant may serve as a potential genetic modifier of HF severity in the context of PA.

Background: Primary Aldosteronism (PA), a form of endocrine hypertension (EH), often manifests as Resistant Hypertension (RHTN). RHTN is an increasingly prevalent clinical condition associated with target organ damage and a poor prognosis. Accurate diagnosis and management of EH and PA are challenging due to their diverse clinical manifestations, complex laboratory findings, and potential drug-drug interactions (DDIs). These DDIs, often overlooked in practice, can complicate the diagnostic and treatment processes. Case Presentation: A 56-year-old man with uncontrolled hypertension was admitted to our hospital. He was suspected of having Primary Aldosteronism (PA) and subclinical Cushing’s Syndrome (SCS) based on elevated aldosterone-to-renin ratio (ARR), captopril challenge test results (CCT), and low-dose dexamethasone suppression test (LDDST) results. Adrenal CT showed mild bilateral adrenal hyperplasia. Despite being on six antihypertensive medications, including spironolactone, his blood pressure remained uncontrollable. His medical history revealed prior use of rifampicin for brucellosis. Rifampicin, a CYP450 inducer, caused drug-drug interactions (DDIs), leading to a false-positive dexamethasone suppression test (DST) and reduced efficacy of antihypertensive drugs. After discontinuing rifampicin, his blood pressure was controlled with fewer medications. One month later, repeated ARR and CCT were still positive. Adrenal venous sampling (AVS) indicated bilateral aldosterone secretion without a dominant side, confirming Idiopathic Hyperaldosteronism (IHA). Targeted treatment with MRA led to partial clinical and biochemical remission of PA. Conclusion: This case highlights the diagnostic and therapeutic challenges of Endocrine Hypertension (EH) and Primary Aldosteronism complicated by CYP450 enzyme inducers. Specifically, the use of rifampicin, a potent CYP450 inducer, resulted in false-positive diagnostic test results and diminished efficacy of antihypertensive medications, thereby contributing to RHTN. When encountering uncontrolled hypertension, particularly when standard treatments fail, awareness of DDIs is crucial for accurate diagnosis and effective management.

Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction, is a major cause of secondary hypertension with significant cardiovascular complications. Current treatments mainly focus on symptom management rather than addressing underlying mechanisms. This study aims to discover novel therapeutic targets for PA using integrated bioinformatics and experimental validation approaches. We employed a systematic approach combining: gene identification through transcriptome-wide association studies (TWAS); causal inference using summary data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (MR) analyses; additional analyses included phenome-wide association analysis, enrichment analysis, protein-protein interaction (PPI) networks, drug repurposing, molecular docking and clinical validation through aldosterone-producing adenomas (APAs) tissue. Through systematic screening and prioritization, we identified 163 PA-associated genes, of which seven emerged as potential drug targets: CEP104, HIP1, TONSL, ZNF100, SHMT1, and two long non-coding RNAs (AC006369.2 and MRPL23-AS1). SHMT1 was identified as the most promising target, showing significantly elevated expression in APAs compared to adjacent non-tumorous tissues. Drug repurposing analysis identified four potential SHMT1-targeting compounds (Mimosine, Pemetrexed, Leucovorin, and Irinotecan), supported by molecular docking studies. The integration of multiple bioinformatics methods and experimental validation successfully identified novel drug targets for hyperaldosteronism. SHMT1, in particular, represents a promising candidate for future therapeutic development. These findings provide new opportunities for developing causative treatments for PA, though further clinical validation is warranted.

Inappropriate aldosterone production relative to sodium status is known to induce arterial hypertension and cause detrimental effects on endothelium and vascular remodeling. This study investigated whether microRNAs (miRs) serve as key mediators of aldosterone’s effects on endothelial dysfunction. Using human umbilical vein endothelial cells (HUVECs) as a model system, we demonstrated that aldosterone treatment suppressed cellular proliferation and migration while promoting senescence. Mechanistically, we observed that aldosterone exposure significantly upregulated miR‐34a expression in HUVECs. The functional significance of miR‐34a was confirmed when specific inhibitors reversed aldosterone’s antiproliferative and prosenescence effects. To elucidate the underlying molecular pathway, we performed comprehensive biological analyses, which revealed that miR‐34a target genes were predominantly associated with the Notch signaling pathway. Western blot analysis further validated that miR‐34a promotes senescence in HUVECs through negative regulation of NOTCH1. Collectively, our findings identify miR‐34a as a crucial mediator of aldosterone‐induced endothelial cell senescence via the NOTCH1 signaling pathway, suggesting its potential as a therapeutic target for aldosterone‐related vascular diseases.

Purpose of review One of the challenges in the diagnosis and management of primary aldosteronism (PA), the most common type of secondary hypertension with curative potential, is the modification of antihypertensive medications. We seek to explore whether these medications can be continued during the diagnostic process of PA to minimize the duration and risks associated with medication adjustments. Recent findings We searched PubMed for eligible original literature between 1990 and 2024 using the following keywords: (screening) AND (primary aldosteronism); (confirmatory) AND (primary aldosteronism); (adrenal vein sampling) AND primary aldosteronism). Some recent studies support the feasibility of PA-related tests and even adrenal vein sampling (AVS) without the need to discontinue antihypertensive medications in certain cases. Summary In this review, we propose a management approach that considers the specific effects of antihypertensive medications on the RAAS axis and the patient's disease phenotype. Based on this, we suggest a strategy that enables the diagnosis of PA in certain patients without discontinuing their antihypertensive medications.

Aldosterone-producing adenoma (APA), characterized by unilaterally excessive aldosterone production, is a common cause of primary aldosteronism. Ferroptosis, a recently raised iron-dependent mode of programmed cell death, has been involved in the development and therapy of various diseases. This study obtained datasets of the mRNA and lncRNA expression profiles for APA and adjacent adrenal gland (AAG) from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and lncRNAs (DE lncRNAs) associated with ferroptosis were identified. Enrichment analyses indicated 89 ferroptosis-related DEGs were primarily enriched in ROS related processes and ferroptosis. Two physical cores, and one combined core were identified in the protein–protein interaction (PPI). DEGs and clinical traits were used in conjunction to screen eight hub genes from two hub modules and 89 DEGs. A competitive endogenous RNA (ceRNA) network was constructed via co-express analysis. Thereafter, molecular docking was used to identify potential targets. Two active compounds, QL-X-138 and MK-1775, bound to AURKA and DUOX1, respectively, with the lowest binding energies. Molecular dynamics simulation verified the stability of the two complexes. In summary, our studies identified eight hub genes and a novel ceRNA regulatory network associated with ferroptosis, wherein QL-X-138 and MK-1775 were considered to be potential drugs for treating APA.

Rationale: Since the introduction of the aldosterone-to-renin ratio (ARR) as a screening tool for primary aldosteronism (PA), there has been a marked increase in the reported prevalence of this condition among hypertensive, even normotensive, subjects. Patient concerns: But ARR as a spot blood draw for estimating a patient’s aldosterone secretory status is influenced by many factors. Diagnoses: Here, we describe a series of patients with biochemically confirmed PA, whose diagnosis was delayed by the initial ARR assessment with non-suppressed renin. Interventions: Patient 1 had a history of resistant hypertension for many years and had a negative initial screening for secondary hypertension (including ARR). At the reevaluation, ARR was close to cutoff still with normal renin after strict and extended drug washout, and the further workup for PA demonstrated a unilateral aldosterone producing adenoma that was surgically removed, with subsequent complete biochemical remission and partial clinical success. Patient 2 was diagnosed with idiopathic hyperaldosteronism combined with obstructive sleep apnea syndrome, which could increase renin resulting in a negative ARR, and finally got a better treatment effect with PA-specific spironolactone, as well as continuous positive airway pressure. Patient 3 with hypokalemia as the main presentation was finally diagnosed with PA after excluding other diseases, and proceeded to laparoscopic adrenalectomy and histologically confirmed an aldosterone producing adenoma. Postoperatively, patient 3 achieved complete biochemical success without any medicine. Outcomes: The clinical status of all three patients was effectively managed, resulting in either complete resolution or notable improvement of their respective conditions. Lessons: After rigorous standardized diagnostic evaluation, there are still many reasons for ARR negative in PA, but they all basically occur in the background of normal or normal-high renin without suppression. A negative screening test result should be repeated and analyzed carefully if this is not consistent with the clinical picture. If, despite a repeatedly negative ARR, clinical suspicion remains high, we recommend consideration of further evaluation, including confirmatory tests and adrenal venous blood sampling (AVS) or even 68Ga-pentixafor PET/CT to better confirm the diagnosis and improve patient outcomes.