Publications

Because aldosterone plays an essential role in electrolytes balance and blood pressure control, primary aldosteronism is considered a cardiorenal disease. However, patients’ lived experiences and over 50,000 published studies attest of deleterious effects far beyond the heart, vasculature, and kidneys.

The Primary Aldosteronism Foundation maintains a database of salient publications with emphasis on commonly studied topics as well as signs, symptoms, and comorbidities associated with excess aldosterone and frequently experienced by patients. New articles and topics of interest are added as they become public.

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Differences in the Clinical and Hormonal Presentation of Patients With Familial and Sporadic Primary Aldosteronism

Abstract/Summary:

The purpose of the study was to compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA). A systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator group (sporadic group). A total of 360 FH (246 FH type I, 73 type II, 29 type III, and 12 type IV) cases and 830 sporadic PA patients were included. Patients with FH-I were younger than sporadic cases, and women were more commonly affected (P = 0.003). In addition, the plasma aldosterone concentration (PAC) was lower, plasma renin activity (PRA) higher, and hypokalemia (P < 0.001) less frequent than in sporadic cases. Except for a younger age (P < 0.001) and higher diastolic blood pressure (P = 0.006), the clinical and hormonal profiles of FH-II and sporadic cases were similar. FH-III had a distinct phenotype, with higher PAC and higher frequency of hypokalemia (P < 0.001), and presented 45 years before sporadic cases. Nevertheless, the clinical and hormonal phenotypes of FH-IV and sporadic cases were similar, with the former being younger and having lower serum potassium levels. In addition to being younger and having a family history of PA, FH-I and III share other typical characteristics. In this regard, FH-I is characterized by a low prevalence of hypokalemia and FH-III by a severe aldosterone excess causing hypokalemia in more than 85% of patients. The clinical and hormonal phenotype of type II and IV is similar to the sporadic cases.

Authors: Marta Araujo-Castro, Paola Parra, Patricia Martín Rojas-Marcos, Miguel Paja Fano, Marga González Boillos, Eider Pascual-Corrales, Ana María García Cano, Jorge Gabriel Ruiz-Sanchez, Almudena Vicente Delgado, Emilia Gómez Hoyos, Rui Ferreira, Iñigo García Sanz, Mònica Recasens Sala, Rebeca Barahona San Millan, María José Picón César, Patricia Díaz Guardiola, Carolina M. Perdomo, Laura Manjón-Miguélez, Rogelio García Centeno, Ángel Rebollo Román, Paola Gracia Gimeno, Cristina Robles Lázaro, Manuel Morales-Ruiz, María Calatayud, Simone Andree Furio Collao, Diego Meneses, Miguel Sampedro Nuñez, Verónica Escudero Quesada, Elena Mena Ribas, Alicia Sanmartín Sánchez, Cesar Gonzalvo Diaz, Cristina Lamas, María del Castillo Tous, Joaquín Serrano Gotarredona, Theodora Michalopoulou Alevras, Eva María Moya Mateo, Felicia A. Hanzu
Keywords: familial primary aldosteronism, sporadic primary aldosteronism
DOI Number: 10.3389/fendo.2024.1336306
Publication Year: 2024

Intraprocedural Cortisol Testing During Adrenal Vein Sampling for Primary Aldosteronism: Weighing the Benefits and Limitations

Abstract/Summary:

Primary aldosteronism (PA) is characterized by renin-independent aldosterone secretion from one or both adrenal glands leading to inappropriate mineralocorticoid receptor (MR) activation and blood pressure elevation. While still woefully underdiagnosed PA is increasingly recognized as the most common yet modifiable form of secondary hypertension. Modern-day prevalence studies demonstrate that 10%–20% of all cases of hypertension are attributable to PA, including a direct association between hypertension severity and PA prevalence. Notably, PA leads to a disproportionately higher risk for cardiovascular, metabolic, and kidney disease compared with essential hypertension, even independent of blood pressure. In the process of evaluating a patient with PA, a key determination to make is whether the source of aldosterone excess lateralizes to one adrenal gland or not. This distinction will guide whether the recommended treatment will involve surgical adrenalectomy (lateralizing PA) or lifelong MR antagonist therapy (nonlateralizing PA). Importantly, a number of observational studies have demonstrated substantially improved long-term health outcomes with adrenalectomy compared with MR antagonist therapy in lateralizing PA. Determination of disease lateralization, and thereby candidacy for adrenalectomy, is a 2-step process including adrenal protocol CT or MRI along with adrenal vein sampling (AVS). CT/MRI alone is generally insufficient to determine disease lateralization as it may produce misleading results,11 and AVS (considered the current “gold standard” for PA lateralization) is typically required prior to proceeding with adrenalectomy.

Authors: Gregory L Hundemer
Keywords: intraprocedural cortisol testing, adrenal vein sampling, AVS
DOI Number: 10.1093/ajh/hpad095
Publication Year: 2023

Bilateral or Unilateral Aldosterone Hypersecretion and Responsiveness to Therapy Are Associated With Differences in Calcium/Phosphate Homeostasis in Patients With Primary Aldosteronism

Abstract/Summary:

Primary aldosteronism is characterized by the autonomous excretion of aldosterone, which may induce bone mineral disorders. A total of 96 patients with primary aldosteronism were analyzed to identify differences in the regulation of serum calcium/phosphate balance between patients with unilateral and bilateral aldosterone hypersecretion and to determine whether or not adrenalectomy or mineralocorticoid receptor blockers affected such differences. Serum phosphate concentrations were significantly lower in patients with unilateral aldosterone hypersecretion than in patients with bilateral aldosterone hypersecretion (2.96±0.45 vs. 3.36±0.55 mg/dL, P<0.05), and recovered after adrenalectomy (2.96±0.45 vs. 3.49±0.32 mg/dL, P<0.01). In patients with bilateral aldosterone hypersecretion, the baseline serum phosphate levels were significantly lower in responders to mineralocorticoid receptor blocker treatment, defined as post-treatment plasma renin activity ≥1 ng/mL/h, than in non-responders. In responders, these levels tended to recover after treatment. A weak negative correlation between the plasma aldosterone concentration (PAC) and serum phosphate was observed, but there were no associations between the PAC and serum calcium concentration or between the aldosterone renin ratio and serum calcium and phosphate concentrations. The effects on calcium/phosphate homeostasis may differ according to the primary aldosteronism subtype.

Authors: Miki Yarita-Kawana, Satoshi Kidoguchi, Yohei Suehiro, Naoki Sugano, Takashi Yokoo
Keywords: calcium, phosphate, calcium/phosphate homeostasis
DOI Number: 10.2169/internalmedicine.3116-23
Publication Year: 2024

Intraprocedural Cortisol Measurement Increases Adrenal Vein Cannulation Success Rate in Primary Aldosteronism: A Systematic Review and Meta-analysis

Abstract/Summary:

This study aimed to explore the effectiveness of intraprocedural cortisol measurement (IPCM) for the technical success rates of bilateral adrenal vein, right adrenal vein (RAV), and left adrenal vein (LAV) cannulation during adrenal vein sampling (AVS). Systematic searches of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were performed from database inception to May 10, 2023, without any restrictions. We estimated the overall effect estimates of outcomes using the Mantel–Haenszel random-effects model. We conducted subgroup analyses, meta-regression, and sensitivity analysis to explore the possible sources of between-study heterogeneity. In total, 3,485 patients from 11 studies (three prospective and eight retrospective) were enrolled. Bilateral selectivity in patients who underwent IPCM during AVS was significantly higher than that in patients who underwent a routine AVS procedure (84% vs. 64%, RR 1.42, 95% confidence interval [CI]: 1.27–1.59, P < 0.01), with significant heterogeneity (I2 = 68%). A 42% relative risk reduction in the failure rate of bilateral adrenal vein cannulation was found in the IPCM group. Moreover, pooled analysis showed a significant increase in the success rates of RAV cannulation (84% vs. 72%, RR 1.21, 95% CI 1.12–1.31, P < 0.01, I2 = 33%) and LAV cannulation (89% vs. 84%, RR 1.05, 95% CI 1.02–1.08, P < 0.01, I2 = 4%) when IPCM was implemented during the AVS procedure compared to the routine AVS procedure. An IPCM-based strategy during AVS appears to have a significant beneficial effect on improving the success rate of bilateral cannulation, RAV cannulation and LAV cannulation.

Authors: Yaqiong Zhou, Huamin Zhang, Jie Luo, Jixin Hou, Qiang Xue, Xiaohan Wang, Hui Guo, Xinquan Wang, Peijian Wang
Keywords: intraprocedural cortisol, cannulation, adrenal vein sampling, AVS
DOI Number: 10.1093/ajh/hpad089
Publication Year: 2023

Clinical Features and Etiology of Recurrent Hypertension After Adrenalectomy

Abstract/Summary:

Patients who undergo adrenalectomy for unilateral primary aldosteronism (PA) may still develop post-surgery hypertension; however, the clinical characteristics and etiology of patients developing recurrent hypertension after adrenalectomy are unclear. We analyzed the records of 43 patients with recurrent elevated blood pressure after adrenalectomy, who were treated at our center. Standard routine clinical screening workup was used to identify the cause of recurrent hypertension. Causes of recurrent hypertension after adrenalectomy included essential hypertension, primary aldosteronism, obstructive sleep apnea, renal artery stenosis, and Takayasu arteritis. Before adrenalectomy, 39.5% of patients were diagnosed with confirmed or suspected PA, primarily through CT imaging. Adrenal venous sampling (AVS) tests were not conducted on any patients, and 72.1% patients underwent partial adrenalectomy. Among all patients, elevated blood pressure was observed in 44.2% immediately post-operation, 18.6% within 1 month, 16.3% in 1–6 months, and 20.9% >6 months after operation. Most patients had hypertension of grade 2 and above. Standard endocrine functional assessment and AVS tests should be performed before adrenalectomy to ensure more accurate diagnosis and favorable post-operative outcomes. Additionally, individuals often develop essential hypertension regardless of past adrenal disease.

Authors: Xilan Dong, Qianhui Ling, Jin Bian, Yuehua Li, Mengjia Chen, Sufang Hao, Wenjun Ma, Huimin Zhang, Jun Cai, Ying Lou
Keywords: recurrent hypertension, post-surgery hypertension
DOI Number: 10.15212/CVIA.2023.0092
Publication Year: 2024

A Comparison of the Performance of 68Ga-Pentixafor PET/CT Versus Adrenal Vein Sampling for Subtype Diagnosis in Primary Aldosteronism

Abstract/Summary:

The objective of the study was to investigate the diagnostic efficiency and prognostic value of 68Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis. We prospectively recruited 26 patients diagnosed with PA. All patients underwent 68Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4. On total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2. Our analysis showed that 68Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. 68Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA.

Authors: Xuan Yin, Kai Ai, Jianguang Luo, Wei Liu, Xiaowei Ma, Lianbo Zhou, Xin Xiang, Xin Su, Yunhua Wang, Yuan Li
Keywords: 68Ga-Pentixafor, PET/CT
DOI Number: 10.3389/fendo.2024.1291775
Publication Year: 2024