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Diagnosis of Primary Aldosteronism: There is No Best, But for Better

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Zhang Bo, chief physician, master tutor, deputy director of the Department of Endocrinology of the China-Japan Friendship Hospital (to preside over the work).He was elected as a member of the standing committee of the Endocrinology Branch of the Chinese Medical Association and served as the deputy head of the pituitary medicine group in 2013,.He was re-elected as a member of the standing committee and served as deputy leader of adrenal science group in 2016.He was re-elected to the standing committee and served as the leader of the adrenal science group in 2019.Chairman of the Diabetes Expert Committee of the National Telemedicine and Internet Medical Center. Convener of Diabetes Internet Alliance of National Telemedicine Center. President of the Endocrinology and Diabetes Branch of the Bethune Spirit Research Association.The leader of the project of "Comprehensive Intervention Technology of Metabolic Syndrome" of the National Eleventh Five-Year Science and Technology Support Plan Project.The Co-Leader of the National Twelfth Five-Year Science and Technology Support Program sub-project "Comprehensive Strengthening Management of Various Components of Metabolic Syndrome and Promotion and Demonstration of Electronic Information Technology Intervention Model".The leader of the project of the National Key Research and Development Program of the 13th Five-Year Study on the Status of Control of Multiple Risk Factors, Risk Prediction Models, Intervention Appropriate Techniques and Management Strategies for High-risk Groups with Diabetes.Take the lead in conducting closed-loop pump research in China.he won the second prize of the Chinese Medical Science and Technology Award in 2011.he won the first prize of Beijing Science and Technology Progress Award in 2012.Participate in the preparation of the national postgraduate textbook: Congenital Adrenal Hyperplasia in Endocrinology.Research direction: basic and clinical research of adrenal diseases, clinical and epidemiological research of diabetes.

E-mail: drbozhang@yahoo.com.

Diagnosis of Primary Aldosteronism: There is No Best, But for Better

Zhang Bo

 

Primary aldosteronism (PA) is the most common cause of endocrine hypertension, which has gradually received clinical attention in recent years. However, at present, there are many defects in the diagnosis of PA, such as inconsistent methods and complicated and cumbersome procedures, which has caused some patients to be missed or even misdiagnosed. Therefore, exploring more accurate and concise diagnostic methods is the hot spot of current PA clinical research. Professor Tian Hao-ming and Chief Physician Ren Yan of Department of Endocrinology and Metabolism of West China Hospital of Sichuan University chaired the topic "Progress in the diagnosis of primary aldosteronism". The topic review "Diagnosis and Research Progress of Primary Aldosteronism" provides a concise explanation of the development of PA diagnosis, and provides a detailed analysis and summary of the latest research progress, difficulties and controversial points in recent years. It helps clinicians understand the whole picture of PA diagnosis more clearly. The clinical research on this topic focuses on the current difficulties and controversies in the diagnosis of PA. The research results have important clinical significance for optimizing and simplifying the diagnosis of PA.

1. Screening

Although the ratio of aldosterone to renin (ARR) is the preferred index for PA screening recommended by the guidelines, because it is a ratio index, it is mainly affected by renin level, so in the case of extremely low renin level, theremay be a false positive. In recent years, a new viewpoint believes that aldosterone levels combined with renin levels (not the ratio between the two) can be directly used for PA screening, and whether this viewpoint can be generally adopted in clinical practice still needs more clinical research support. The “Exploration of the Value of Different Methods for Screening Primary Aldosteronism” in this topic shows the logistic regression models including upright plasma aldosterone concentration (PAC), upright plasma renin activity (PRA) and lowest serum potassium is better than ARR.

The traditional detection method for aldosterone and renin is radioimmunoassay. In recent years, new detection methods such as chemiluminescence and mass spectrometry have been gradually introduced into clinical practice, but they have not been developed in large-scale clinical practice. Chemiluminescence method has the advantages of fast detection speed, automation, no radiation, etc. Mass spectrometry has the advantages of high throughput, simple sample preparation process, and low sample volume, and can also measure steroid hormone spectrum. Introducing mass spectrometry into clinical practice will have a significant impact on the diagnosis of PA, but the equipment investment cost of this method is high and the method will take some time to explore.

In addition, new PA biomarkers are constantly being explored. Urinary exosomes are a promising biomarker for PA, but their clinical value needs further study.

2. Confirmatory Diagnosis

The current guidelines recommend four types of diagnostic tests: fludrocortisone suppression test (FST), saline infusion test (SIT), captopril challenge test (CCT), and oral sodium loading test. These four tests are the biochemical diagnosis criteria for PA, and there is no evidence to show which is the best. Because FST and oral sodium loading test are cumbersome, time-consuming, or no fludrocortisone in China, these two tests are rarely used in China, and the commonly used diagnostic tests are CCT and SIT.Clinical Diagnosis and Treatment of Primary Aldosteronism in West China Hospital of Sichuan University From 2009 to 2018 in this topic shows that only 33.27% of PA patients underwent CCT and / or SST in West China Hospital of Sichuan University from 2009 to 2016, while the proportion of PA patients who underwent CCT and/or SST in 2017−2018 increased to 79.67%.

Clinically, SIT is usually performed in a supine position. The disadvantage of supine SIT is that the patient must be hospitalized to complete this examination. Some studies have shown that the sensitivity of seated SIT is better than that of supine SIT, and it is also valuable for the diagnosis of PA subtyping. Therefore, the seated SIT is expected to replace the supine SIT and become a more convenient diagnostic test.

The guideline recommends that the PAC inhibition rate after CCT is less than 30% as the diagnostic criteria for PA, and our country's research shows that the diagnostic efficiency of PAC after CCT is better than the PAC inhibition rate, indicating that PAC as a diagnostic indicator after CCT may be more suitable for the Chinese population.

Meta-analysis showed that there was no significant difference in diagnostic efficacy between CCT and SIT. Compared with SIT, CCT has fewer side effects, takes less time, is easy to operate, and can be performed in an outpatient clinic. Therefore, the clinical operability of CCT is better than SIT.

Other new diagnostic tests (such as valsartan test, Dexamethasone, captopril and valsartan combined test) are still being explored.

 

3. Subtype Classification

Subtyping is the key and difficult part of the PA diagnosis. The identification of patients with unilateral lesions and surgical treatment can significantly improve the patient's prognosis. Methods currently used for subtypeclassification include: adrenal venous blood sampling (AVS), imaging examination, postural testing, ACTH stimulation test, and clinical prediction models, among which AVS has the highest accuracy.

At present, the biggest controversy about the diagnosis of PA subtyping is whether adrenal CT can directly replace AVS. Adrenal CT scan is the main method of adrenal imaging because of its advantages of simplicity, accuracy and non-invasiveness. However, despite the highest accuracy, AVS also has many shortcomings, including:  invasive examination, radiation exposure, risk of complications such as adrenal vein rupture, thrombosis, hematoma;  high cost, high technical requirements, many hospitals cannot implement this operation, and the variability of failure rates between different hospitals or doctors is large; different medical centers may use different operating procedures and diagnostic cut-off values, making interpretation of the results difficult. Throughout the studies in recent years, most studies have shown that CT cannot replace AVS at present, but can assist in the selection of PA patients who need AVS.

The topic "The Value of Serum Potassium and the Ratio of Serum Sodium to Potassium in The Differential Diagnosis of Primary Aldosteronism" shows that the ratio of blood potassium to sodium potassium after SIT is not sensitive for PA subtyping. Some other new classification methods such as imaging functional imaging, ACTH stimulation test and clinical prediction model, etc. Although some studies have shown that they have certain value in the diagnosis of classification, they still cannot replace AVS. Although AVS is not ideal, it is still the most accurate diagnostic method for typing. While exploring other better methods, we should also strengthen the formal training of medical personnel, adopt standardized procedures, and select appropriate cut-off values ​​to improve the success rate and accuracy of AVS.

In summary, PA is no longer considered to be a rare disease. As the most common cause of secondary hypertension, it should not be missed and misdiagnosed. Therefore, it is very important to diagnose PA according to guidelines in clinical practice. In the past 10 years, West China Hospital of Sichuan University has significantly improved the ability of diagnosis and treatment of PA by standardizing the diagnosis and treatment process and establishing a multidisciplinary joint diagnosis and treatment team. At present, there are deficiencies in various PA diagnostic methods, and exploring better diagnostic methods is still the focus of current PA research.


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