1
|
Yarita-Kawana M, Kidoguchi S, Suehiro Y, Sugano N, Yokoo T. Bilateral or Unilateral Aldosterone Hypersecretion and Responsiveness to Therapy Are Associated with Differences in Calcium/Phosphate Homeostasis in Patients with Primary Aldosteronism. Intern Med 2024; 63:2605-2612. [PMID: 38403766 PMCID: PMC11518601 DOI: 10.2169/internalmedicine.3116-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Accepted: 12/25/2023] [Indexed: 02/27/2024] Open
Abstract
Introduction Primary aldosteronism is characterized by the autonomous excretion of aldosterone, which may induce bone mineral disorders. Methods 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. Results 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. Conclusion The effects on calcium/phosphate homeostasis may differ according to the primary aldosteronism subtype.
Collapse
Affiliation(s)
- Miki Yarita-Kawana
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Satoshi Kidoguchi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Yohei Suehiro
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Naoki Sugano
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Japan
| |
Collapse
|
2
|
Hua Y, He Q. Comparison between screening for primary aldosteronism with and without drug adjustment. Blood Press 2024; 33:2350981. [PMID: 38824645 DOI: 10.1080/08037051.2024.2350981] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 04/29/2024] [Indexed: 06/04/2024]
Abstract
OBJECTIVE Few studies have evaluated the performance of non-drug-adjusted primary aldosteronism (PA) screening. Therefore, we aimed to examine the consistency between PA screening results with and without drug adjustment and to explore the effectiveness of screening without drug adjustment. METHODS This prospective study included 650 consecutive patients with a high risk of incidence PA. Patients who initially screened positive underwent rescreening with drug adjustments and confirmatory tests. Regarding the remaining patients, one of every three consecutive patients underwent rescreening with drug adjustments and confirmatory tests. The changes in aldosterone and renin concentrations were compared between patients with essential hypertension (EH) and those with PA before and after drug adjustment. Sensitivity and specificity were used to assess the diagnostic performance of screening without drug adjustment, using the confirmatory test results as the reference. RESULTS We screened 650 patients with hypertension for PA. Forty-nine patients were diagnosed with PA and 195 with EH. Regarding drugs, 519 patients were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or diuretics alone or in combination. Forty-one patients were taking beta-blockers. Ninety patients were taking beta-blockers in combination with other drugs. In patients treated with ACEIs, ARBs, CCBs, or diuretics alone, or in combination, or beta-blockers alone, PA positivity was determined using the criteria, aldosterone-to-renin ratio (ARR) >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, and negativity, using the criteria, ARR <9 pg/mL/pg/mL; the sensitivity and specificity were 94.7% and 94.5%, respectively. After drug adjustment, the sensitivity and specificity of screening were 92.1% and 89%, respectively. CONCLUSIONS In patients not treated with beta-blockers combined with others, when ARR >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, or, ARR <9 pg/mL/pg/mL, non-drug-adjusted screening results were identical to with drug adjustment. Non-drug-adjusted screening could reduce the chance of medication adjustment, enable patients to continue their treatments and avoiding adverse effects, is of clinical importance.
Collapse
Affiliation(s)
- Yanlong Hua
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Qing He
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| |
Collapse
|
3
|
Zhu R, Shagjaa T, Rossitto G, Caroccia B, Seccia TM, Gregori D, Rossi GP. Exclusion Tests in Unilateral Primary Aldosteronism (ExcluPA) Study. J Clin Endocrinol Metab 2023; 108:496-506. [PMID: 36373399 DOI: 10.1210/clinem/dgac654] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 11/07/2022] [Accepted: 11/08/2022] [Indexed: 11/16/2022]
Abstract
CONTEXT Determining the diagnostic accuracy of "exclusion" tests for primary aldosteronism (PA) compared to the aldosterone to renin ratio (ARR) is fundamental to avoid invasive subtyping in false-positive patients at screening. OBJECTIVE To assess the accuracy of exclusion tests for PA using the diagnosis of unilateral PA as reference. METHODS PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies published from January 1, 1970, to December 31, 2021, meeting tight quality criteria. Data were extracted following the PRISMA methodology. We performed a two-stage meta-analysis that entailed an exploratory and a validation phase based on a "golden" or "gold" diagnostic standard, respectively. Pooled specificity, negative likelihood ratio, diagnostic odds ratio, and summary area under the ROC curve (sAUROC) were calculated to analyze the accuracy of exclusion tests. RESULTS A meta-analysis of 31 datasets comprising a total of 4242 patients fulfilling the predefined inclusion criteria found that pooled accuracy estimates (sAUROC) did not differ between the ARR (0.95; 95% CI, 0.92-0.98), the captopril challenge test (CCT) (0.92; 95% CI, 0.88-0.97), and the saline infusion test (SIT) (0.96; 95% CI, 0.94-0.99). Solid information could not be obtained for the fludrocortisone suppression test and the furosemide upright test, which were assessed in only 1 study each. CONCLUSION The apparently high diagnostic accuracy of the CCT and the SIT was due to the selection of patients with an elevated ARR and thus a high pretest probability of unilateral PA; however, neither test furnished a diagnostic gain over the ARR. Therefore, the systematic use of these exclusion tests in clinical practice is not justified by available evidence.
Collapse
Affiliation(s)
- Rui Zhu
- Internal & Emergency Medicine Unit, Department of Medicine - DIMED, University of Padua, 35128 Padua, Italy
- Department of Endocrinology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, 610072 Chengdu, China
| | - Tungalagtamir Shagjaa
- Internal & Emergency Medicine Unit, Department of Medicine - DIMED, University of Padua, 35128 Padua, Italy
- Department of Neurology, Mongolian National University of Medical Sciences, 14200 Ulaanbaatar, Mongolia
| | - Giacomo Rossitto
- Internal & Emergency Medicine Unit, Department of Medicine - DIMED, University of Padua, 35128 Padua, Italy
- School of Cardiovascular & Metabolic Health, University of Glasgow, 126 University Place, G12 8TA Glasgow, UK
| | - Brasilina Caroccia
- Internal & Emergency Medicine Unit, Department of Medicine - DIMED, University of Padua, 35128 Padua, Italy
| | - Teresa Maria Seccia
- Internal & Emergency Medicine Unit, Department of Medicine - DIMED, University of Padua, 35128 Padua, Italy
| | - Dario Gregori
- Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, 35128 Padua, Italy
| | - Gian Paolo Rossi
- Internal & Emergency Medicine Unit, Department of Medicine - DIMED, University of Padua, 35128 Padua, Italy
| |
Collapse
|
4
|
Naruse M, Katabami T, Shibata H, Sone M, Takahashi K, Tanabe A, Izawa S, Ichijo T, Otsuki M, Omura M, Ogawa Y, Oki Y, Kurihara I, Kobayashi H, Sakamoto R, Satoh F, Takeda Y, Tanaka T, Tamura K, Tsuiki M, Hashimoto S, Hasegawa T, Yoshimoto T, Yoneda T, Yamamoto K, Rakugi H, Wada N, Saiki A, Ohno Y, Haze T. Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021. Endocr J 2022; 69:327-359. [PMID: 35418526 DOI: 10.1507/endocrj.ej21-0508] [Citation(s) in RCA: 122] [Impact Index Per Article: 40.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.
Collapse
Affiliation(s)
- Mitsuhide Naruse
- Endocrine Center and Clinical Research Center, Ijinkai Takeda General Hospital, Kyoto 601-1495, Japan
- Clinical Research Institute of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Takuyuki Katabami
- Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University, Yokohama City Seibu Hospital, Yokohama 241-0811, Japan
| | - Hirotaka Shibata
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University, Yufu 879-5593, Japan
| | - Masakatsu Sone
- Division of Metabolism and Endocrinology, Department of Internal Medicine, St. Marianna University, Kawasaki 216-8511, Japan
| | | | - Akiyo Tanabe
- Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo 162-8655, Japan
| | - Shoichiro Izawa
- Division of Endocrinology and Metabolism, Tottori University Faculty of Medicine, Yonago 683-8504, Japan
| | - Takamasa Ichijo
- Department of Diabetes and Endocrinology, Saiseikai Yokohamashi Tobu Hospital, Yokohama 230-0012, Japan
| | - Michio Otsuki
- Department of Endocrinology, Tokyo Women's Medical University, Tokyo 162-8666, Japan
| | - Masao Omura
- Minato Mirai Medical Square, Yokohama, 220-0012 Japan
| | - Yoshihiro Ogawa
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
- Department of Endocrine and Metabolic Diseases/Diabetes Mellitus, Kyushu University Hospital, Fukuoka 812-8582, Japan
| | - Yutaka Oki
- Department of Metabolism and Endocrinology, Hamamatsu Kita Hospital, Hamamatsu 431-3113, Japan
| | - Isao Kurihara
- Department of Medical Education, National Defense Medical College, Tokorozawa 359-8513, Japan
- Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine, Tokyo 160-8582, Japan
| | - Hiroki Kobayashi
- Division of Nephrology, Hypertension and Endocrinology, Nihon University School of Medicine, Tokyo 173-8610, Japan
| | - Ryuichi Sakamoto
- Department of Endocrine and Metabolic Diseases/Diabetes Mellitus, Kyushu University Hospital, Fukuoka 812-8582, Japan
| | - Fumitoshi Satoh
- Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan
| | - Yoshiyu Takeda
- Department of Endocrinology and Metabolism, Kanazawa University Hospital, Kanazawa 920-8641, Japan
| | - Tomoaki Tanaka
- Department of Molecular Diagnosis, Chiba University, Chiba 260-8677, Japan
| | - Kouichi Tamura
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
| | - Mika Tsuiki
- Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan
| | - Shigeatsu Hashimoto
- Department of Endocrinology, Metabolism, Diabetology and Nephrology, Fukushima Medical University Aizu Medical Center, Aizu 969-3492, Japan
| | - Tomonobu Hasegawa
- Department of Pediatrics, Keio University School of Medicine, Tokyo 160-0016, Japan
| | - Takanobu Yoshimoto
- Department of Diabetes and Endocrinology, Tokyo Metropolitan Hiroo Hospital, Tokyo 150-0013, Japan
| | - Takashi Yoneda
- Department of Health Promotion and Medicine of the Future, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
| | - Koichi Yamamoto
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
| | - Hiromi Rakugi
- Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
| | - Norio Wada
- Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo 060-8604, Japan
| | - Aya Saiki
- Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan
| | - Youichi Ohno
- Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
| | - Tatsuya Haze
- Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan
- Department of Nephrology and Hypertension, Yokohama City University Medical Center, Yokohama 232-0024, Japan
| |
Collapse
|
5
|
Kidoguchi S, Sugano N, Kawauchi R, Nakashima D, Hayashi-Ishikawa N, Tokudome G, Yokoo T. Evaluation of various confirmatory tests for the diagnosis of aldosterone-producing adenoma. J Renin Angiotensin Aldosterone Syst 2021; 21:1470320320919610. [PMID: 32370649 PMCID: PMC7227155 DOI: 10.1177/1470320320919610] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Introduction: Adrenal venous sampling is useful for discriminating unilateral and bilateral hypersecretion in patients with primary aldosteronism, but it is relatively invasive. To determine the site of hypersecretion more non-invasively, we evaluated predictors of unilateral hypersecretion. Materials and methods: We evaluated the baseline characteristics and the results of confirmatory tests of 123 patients with primary aldosteronism who underwent adrenal venous sampling. Results: Unilateral hypersecretion was identified in 22.0%. The plasma aldosterone concentration and aldosterone–renin ratio were significantly higher and serum potassium concentration and plasma renin activity were significantly lower in patients with unilateral hypersecretion. Plasma aldosterone concentrations after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were significantly higher among patients with unilateral hypersecretion. The plasma aldosterone concentration reduction ratio in saline infusion test and plasma aldosterone concentration elevation ratio during rapid adrenocorticotropic hormone stimulation test were significantly higher in patients with unilateral hypersecretion. However, areas under the curve for these parameters were not superior to the values after confirmatory tests. Conclusions: The plasma aldosterone concentration values after captopril challenge test, saline infusion test and rapid adrenocorticotropic hormone stimulation test were useful for identifying patients with unilateral hypersecretion. However, value changes or ratios during confirmatory tests are less useful for this aim.
Collapse
Affiliation(s)
- Satoshi Kidoguchi
- Division of Nephrology and Hypertension, The Jikei University School of Medicine, Japan
| | - Naoki Sugano
- Division of Nephrology and Hypertension, The Jikei University School of Medicine, Japan
| | - Ruri Kawauchi
- Division of Nephrology and Hypertension, The Jikei University School of Medicine, Japan
| | - Daisuke Nakashima
- Division of Nephrology and Hypertension, The Jikei University School of Medicine, Japan
| | | | - Goro Tokudome
- Division of Nephrology and Hypertension, The Jikei University School of Medicine, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, The Jikei University School of Medicine, Japan
| |
Collapse
|
6
|
Egan C, Greenberg J, Fahey TJ. Endocrine Hypertensive Emergencies. ENDOCRINE SURGERY COMPREHENSIVE BOARD EXAM GUIDE 2021:1013-1037. [DOI: 10.1007/978-3-030-84737-1_42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
7
|
Chen KM, Lee BC, Chen PT, Liu KL, Lin KH, Chang CC, Wu TH, Hong JS, Lin YH. Evaluation of Abdominal Computed Tomography Scans for Differentiating the Discrepancies in Abdominal Adipose Tissue Between Two Major Subtypes of Primary Aldosteronism. Front Endocrinol (Lausanne) 2021; 12:647184. [PMID: 34335463 PMCID: PMC8323492 DOI: 10.3389/fendo.2021.647184] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 05/14/2021] [Indexed: 11/26/2022] Open
Abstract
The aim of this study was to analyze the differences in the distribution of abdominal adipose tissue between the two subtypes of primary aldosteronism (PA) using abdominal computed tomography. We retrospectively analyzed patients diagnosed as having essential hypertension (EH) or PA from the prospectively collected Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Patients with PA were divided into the subgroups of idiopathic hyperaldosteronism (IHA) and unilateral aldosterone-producing adenoma (APA). Patients' basic clinicodemographic data were collected, and a self-developed CT-based software program was used to quantify the abdominal adiposity indexes, including visceral adipose tissue (VAT) area, VAT ratio, waist circumference (WC), subcutaneous adipose tissue (SAT) area, and SAT ratio. We included 190 patients with EH and 436 patients with PA (238 with IHA and 198 with APA). The APA group had significantly lower abdominal adiposity indexes than the other groups. We also found negative correlations of aldosterone-to-renin ratio (ARR) with VAT area, VAT ratio, WC, and body mass index (BMI) in the APA group. After propensity score matching (which left 184 patients each in the IHA and APA groups), patients in the APA group still had significantly lower WC, SAT area, SAT ratio, and VAT ratio than those in the IHA group. Furthermore, logistic regression analysis indicated that lower probability of abdominal obesity was significantly related to patients with APA. Our data revealed that the distribution of abdominal adipose tissue was similar in patients with IHA and those with EH, but the abdominal adiposity indexes were significantly lower in patients with APA than in those with IHA and EH.
Collapse
Affiliation(s)
- Kuan-Ming Chen
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Industrial Ph.D. Program of Biomedical Science and Engineering, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan
- Industrial Ph.D. Program of Biomedical Science and Engineering, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Bo-Ching Lee
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Po-Ting Chen
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kao-Lang Liu
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| | - Kuan-Heng Lin
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Industrial Ph.D. Program of Biomedical Science and Engineering, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan
- Industrial Ph.D. Program of Biomedical Science and Engineering, School of Biomedical Science and Engineering, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Chin-Chen Chang
- Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Department and Graduate Institute of Forensic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- *Correspondence: Chin-Chen Chang, ; Tung-Hsin Wu,
| | - Tung-Hsin Wu
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- *Correspondence: Chin-Chen Chang, ; Tung-Hsin Wu,
| | - Jia-Sheng Hong
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
- Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Yen-Hung Lin
- Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
| |
Collapse
|
8
|
High Efficiency and Problems of Chemiluminescence Assay-Detected Aldosterone-To-Renin Ratio in Practical Primary Aldosteronism Screening. Int J Hypertens 2020; 2020:3934212. [PMID: 32908690 PMCID: PMC7474363 DOI: 10.1155/2020/3934212] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 07/08/2020] [Accepted: 07/16/2020] [Indexed: 11/18/2022] Open
Abstract
Primary aldosteronism is a main cause of secondary hypertension which can be effectively treated. The screening test for primary aldosteronism is benefit for minimizing damage to the patient. In the previous retrospective study, we obtained the optimal cutoff value of aldosterone-to-renin ratio detected by chemiluminescence assay, a newly developing method, and prompted its high efficiency in primary aldosteronism screening in upright position. In this study, we want to evaluate its efficiency in practical work. We used this ratio to continuously screen 238 patients, and 58 patients were finally diagnosed with primary aldosteronism. We found it had 86.13% accuracy rate in the upright position compared with the final clinical diagnosis. False negative and positive rates were 13.79% and 13.89%. Diagnostic sensitivity and specificity were 86.21% and 86.11%, which are slightly different from results in our previous study. False negative rate can be improved by combining the aldosterone-to-renin ratio with aldosterone concentration. We also found impaired glucose tolerance may be a reason for high false positive rate. Besides, chemiluminescence assay may be interfered in aldosterone detection. Although it has some shortcomings, chemiluminescence assay-detected aldosterone-to-renin ratio is a highly effective index for screening primary aldosteronism in practice.
Collapse
|
9
|
Tirosh A, Hannah-Shmouni F, Lyssikatos C, Belyavskaya E, Zilbermint M, Abraham SB, Lodish MB, Stratakis CA. Obesity and the diagnostic accuracy for primary aldosteronism. J Clin Hypertens (Greenwich) 2017; 19:790-797. [PMID: 28612447 DOI: 10.1111/jch.13041] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2017] [Revised: 03/17/2017] [Accepted: 03/26/2017] [Indexed: 12/11/2022]
Abstract
The effects of body mass index on the diagnostic accuracy of primary aldosteronism (PA) are inconsistent and yet important considering the high prevalence and frequent co-occurrence of obesity and hypertension. The current study included 59 adult patients who underwent a stepwise evaluation for PA, using aldosterone to renin ratio for case detection and plasma aldosterone concentration after saline suppression test and/or 24-hour urinary aldosterone after oral sodium loading for case confirmation. Body mass index had a quadratic (U-shaped) correlation with plasma aldosterone concentration, plasma renin activity, aldosterone to renin ratio, and plasma aldosterone concentration after saline suppression test. Among patients with a body mass index ≥30 kg/m2 , the aldosterone to renin ratio yielded lower case detection accuracy of PA. We conclude that obesity results in a nonlinear correlation with plasma aldosterone concentration, plasma renin activity, and aldosterone to renin ratio, which affects the accuracy of case detection for PA. Patients with a body mass index ≥30 kg/m2 are less accurately identified as having PA when saline suppression and/or oral salt loading tests are used for case confirmation.
Collapse
Affiliation(s)
- Amit Tirosh
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Fady Hannah-Shmouni
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Charalampos Lyssikatos
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Elena Belyavskaya
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Mihail Zilbermint
- Division of Endocrinology, Diabetes, and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Suburban Hospital, Bethesda, MD, USA
| | - Smita B Abraham
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Maya B Lodish
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Constantine A Stratakis
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| |
Collapse
|
10
|
Buonacera A, Stancanelli B, Malatino L. Endocrine Tumors Causing Arterial Hypertension: Pathophysiological Mechanisms and Clinical Implications. High Blood Press Cardiovasc Prev 2017; 24:217-229. [PMID: 28405904 DOI: 10.1007/s40292-017-0200-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2017] [Accepted: 04/03/2017] [Indexed: 11/30/2022] Open
Abstract
Some tumors are a relatively rare and amendable cause of hypertension, often associated with a higher cardiovascular morbidity and mortality, as compared with that of both general population and patients with essential hypertension. This worse prognosis is not entirely related to blood pressure increase, because the release of substances from the tumor can directly influence blood pressure behavior. Diagnostic approach is challenging and needs a deep knowledge of the different neuro-hormonal and genetic mechanisms determining blood pressure increase. Surgical tumor removal can, but not always, cause blood pressure normalization, depending on how early was tumor detection, since a long-standing history of hypertension is often associated with a much weaker effect on blood pressure. Moreover, target organ damage can be affected by the substances themselves released by the tumors as well as by tumor removal. In this review we consider the phenotype and genetic features of patients with tumor-induced hypertension and focus on their diagnostic work-up.
Collapse
Affiliation(s)
- Agata Buonacera
- From the Academic Unit of Internal Medicine and Hypertension Centre, Department of Clinical and Experimental Medicine, University of Catania, c/o Cannizzaro Hospital, Via Messina 829, 95126, Catania, Italy
| | - Benedetta Stancanelli
- From the Academic Unit of Internal Medicine and Hypertension Centre, Department of Clinical and Experimental Medicine, University of Catania, c/o Cannizzaro Hospital, Via Messina 829, 95126, Catania, Italy
| | - Lorenzo Malatino
- From the Academic Unit of Internal Medicine and Hypertension Centre, Department of Clinical and Experimental Medicine, University of Catania, c/o Cannizzaro Hospital, Via Messina 829, 95126, Catania, Italy.
| |
Collapse
|
11
|
Primary Aldosteronism: Diagnosis and Management. Am J Med Sci 2016; 352:391-398. [PMID: 27776721 DOI: 10.1016/j.amjms.2016.06.015] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Revised: 06/14/2016] [Accepted: 06/24/2016] [Indexed: 11/21/2022]
Abstract
Primary aldosteronism (PA) is an important and commonly unrecognized cause of secondary hypertension. Idiopathic hyperaldosteronism and aldosterone-producing adenomas account for more than 95% of PA and are characterized, respectively, by bilateral or unilateral involvement of the adrenal glands. When there is suspicion for the presence of PA, a plasma aldosterone to renin ratio should be obtained initially. Localization to determine adrenal gland involvement is done by imaging, with computerized tomography or magnetic resonance imaging. After imaging, adrenal vein sampling is done to establish treatment options. Patients with unilateral disease, who are good surgical candidates, are most appropriately managed with adrenalectomy. A biochemical cure is almost certain following adrenalectomy; however, only 30-50% of patients would show adequate blood pressure improvement. Patients with bilateral adrenal disease and those believed not to be surgical candidates are managed with mineralocorticoid antagonists.
Collapse
|
12
|
Douillard C, Houillier P, Nussberger J, Girerd X. SFE/SFHTA/AFCE Consensus on Primary Aldosteronism, part 2: First diagnostic steps. ANNALES D'ENDOCRINOLOGIE 2016; 77:192-201. [PMID: 27177498 DOI: 10.1016/j.ando.2016.02.003] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Revised: 02/01/2016] [Accepted: 02/01/2016] [Indexed: 12/09/2022]
Abstract
In patients with suspected primary aldosteronism (PA), the first diagnostic step, screening, must have high sensitivity and negative predictive value. The aldosterone-to-renin ratio (ARR) is used because it has higher sensitivity and lower variability than other measures (serum potassium, plasma aldosterone, urinary aldosterone). ARR is calculated from the plasma aldosterone (PA) and plasma renin activity (PRA) or direct plasma renin (DR) values. These measurements must be taken under standard conditions: in the morning, more than 2hours after awakening, in sitting position after 5 to 15minutes, with normal dietary salt intake, normal serum potassium level and without antihypertensive drugs significantly interfering with the renin-angiotensin-aldosterone system. To rule out ARR elevation due to very low renin values, ARR screening is applied only if aldosterone is>240pmol/l (90pg/ml); DR values<5mIU/l are assimilated to 5mIU/l and PRA values<0.2ng/ml/h to 0.2ng/ml/h. We propose threshold ARR values depending on the units used and a conversion factor (pg to mIU) for DR. If ARR exceeds threshold, PA should be suspected and exploration continued. If ARR is below threshold or if plasma aldosterone is<240pmol/l (90pg/ml) on two measurements, diagnosis of PA is excluded.
Collapse
Affiliation(s)
- Claire Douillard
- Service d'endocrinologie et des maladies métaboliques, centre hospitalier régional universitaire de Lille, 59037 Lille, France.
| | - Pascal Houillier
- Département des maladies rénales et métaboliques, hôpital européen Georges-Pompidou, Assistance publique-Hôpitaux de Paris, 75015 Paris, France.
| | - Juerg Nussberger
- Service de médecine interne, unité vasculaire et d'hypertension, centre hospitalier universitaire de Lausanne, CH-1011 Lausanne, Switzerland.
| | - Xavier Girerd
- Pôle cœur métabolisme, unité de prévention cardiovasculaire, groupe hospitalier universitaire Pitié-Salpêtrière, 83, boulevard de l'Hôpital, 75013 Paris, France
| |
Collapse
|
13
|
Thomas RM, Ruel E, Shantavasinkul PC, Corsino L. Endocrine hypertension: An overview on the current etiopathogenesis and management options. World J Hypertens 2015; 5:14-27. [PMID: 26413481 PMCID: PMC4582789 DOI: 10.5494/wjh.v5.i2.14] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2014] [Revised: 12/06/2014] [Accepted: 03/05/2015] [Indexed: 02/06/2023] Open
Abstract
Endocrine causes of secondary hypertension include primary aldosteronism, pheochromocytoma, cushing’s syndrome, hyperparathyroidism and hypo- and hyperthyroidism. They comprise 5%-10% of the causes of secondary hypertension. Primary hyperaldosteronism, the most common of the endocrine cause of hypertension often presents with resistant or difficult to control hypertension associated with either normo-or hypokalemia. Pheochromocytoma, a great mimicker of many conditions, is associated with high morbidity and mortality if left untreated. A complete history including pertinent family history, physical examination along with a high index of suspicion with focused biochemical and radiological evaluation is important to diagnose and effectively treat these conditions. The cost effective targeted genetic screening for current known mutations associated with pheochromocytoma are important for early diagnosis and management in family members. The current review focuses on the most recent evidence regarding causes, clinical features, methods of diagnosis, and management of these conditions. A multidisciplinary approach involving internists, endocrinologists and surgeons is recommended in optimal management of these conditions.
Collapse
|
14
|
Ducher M, Mounier-Véhier C, Lantelme P, Vaisse B, Baguet JP, Fauvel JP. Reliability of a Bayesian network to predict an elevated aldosterone-to-renin ratio. Arch Cardiovasc Dis 2015; 108:293-9. [DOI: 10.1016/j.acvd.2014.09.011] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Accepted: 09/04/2014] [Indexed: 01/21/2023]
|
15
|
Ardhanari S, Kannuswamy R, Chaudhary K, Lockette W, Whaley-Connell A. Mineralocorticoid and apparent mineralocorticoid syndromes of secondary hypertension. Adv Chronic Kidney Dis 2015; 22:185-95. [PMID: 25908467 DOI: 10.1053/j.ackd.2015.03.002] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 03/02/2015] [Accepted: 03/04/2015] [Indexed: 11/11/2022]
Abstract
The mineralocorticoid aldosterone is a key hormone in the regulation of plasma volume and blood pressure in man. Excessive levels of this mineralocorticoid have been shown to mediate metabolic disorders and end-organ damage more than what can be attributed to its effects on blood pressure alone. Inappropriate excess levels of aldosterone contribute significantly to the cardiorenal metabolic syndrome and target organ injury that include atherosclerosis, myocardial hypertrophy, fibrosis, heart failure, and kidney disease. The importance of understanding the role of excess mineralocorticoid hormones such as aldosterone in resistant hypertension and in those with secondary hypertension should be visited. Primary aldosteronism is one of the commonly identified causes of hypertension and is treatable and/or potentially curable. We intend to review the management of mineralocorticoid-induced hypertension in the adult population along with other disease entities that mimic primary aldosteronism.
Collapse
|
16
|
Piaditis G, Markou A, Papanastasiou L, Androulakis II, Kaltsas G. Progress in aldosteronism: a review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. Eur J Endocrinol 2015; 172:R191-203. [PMID: 25538205 DOI: 10.1530/eje-14-0537] [Citation(s) in RCA: 76] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Primary aldosteronism (PA) secondary to excessive and/or autonomous aldosterone secretion from the renin-angiotensin system accounts for ∼10% of cases of hypertension and is primarily caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenomas (APAs). Although the diagnosis has traditionally been supported by low serum potassium levels, normokalaemic and even normotensive forms of PA have been identified expanding further the clinical phenotype. Moreover, recent evidence has shown that serum aldosterone correlates with increased blood pressure (BP) in the general population and even moderately raised aldosterone levels are linked to increased cardiovascular morbidity and mortality. In addition, aldosterone antagonists are effective in BP control even in patients without evidence of dysregulated aldosterone secretion. These findings indicate a higher prevalence of aldosterone excess among hypertensive patients than previously considered that could be attributed to disease heterogeneity, aldosterone level fluctuations related to an ACTH effect or inadequate sensitivity of current diagnostic means to identify apparent aldosterone excess. In addition, functioning aberrant receptors expressed in the adrenal tissue have been found in a subset of PA cases that could also be related to its pathogenesis. Recently a number of specific genetic alterations, mainly involving ion homeostasis across the membrane of zona glomerulosa, have been detected in ∼50% of patients with APAs. Although specific genotype/phenotype correlations have not been clearly identified, differential expression of these genetic alterations could also account for the wide clinical phenotype, variations in disease prevalence and performance of diagnostic tests. In the present review, we critically analyse the current means used to diagnose PA along with the role that ACTH, aberrant receptor expression and genetic alterations may exert, and provide evidence for an increased prevalence of aldosterone dysregulation in patients with essential hypertension and pre-hypertension.
Collapse
Affiliation(s)
- George Piaditis
- Department of Endocrinology and Diabetes CenterG. Gennimatas Hospital, 154 Mesogion Avenue, 11527 Holargos, Athens, Greece andDepartment of PathophysiologyNational University of Athens, Mikras Asias 75, 11527 Athens, Greece
| | - Athina Markou
- Department of Endocrinology and Diabetes CenterG. Gennimatas Hospital, 154 Mesogion Avenue, 11527 Holargos, Athens, Greece andDepartment of PathophysiologyNational University of Athens, Mikras Asias 75, 11527 Athens, Greece
| | - Labrini Papanastasiou
- Department of Endocrinology and Diabetes CenterG. Gennimatas Hospital, 154 Mesogion Avenue, 11527 Holargos, Athens, Greece andDepartment of PathophysiologyNational University of Athens, Mikras Asias 75, 11527 Athens, Greece
| | - Ioannis I Androulakis
- Department of Endocrinology and Diabetes CenterG. Gennimatas Hospital, 154 Mesogion Avenue, 11527 Holargos, Athens, Greece andDepartment of PathophysiologyNational University of Athens, Mikras Asias 75, 11527 Athens, Greece Department of Endocrinology and Diabetes CenterG. Gennimatas Hospital, 154 Mesogion Avenue, 11527 Holargos, Athens, Greece andDepartment of PathophysiologyNational University of Athens, Mikras Asias 75, 11527 Athens, Greece
| | - Gregory Kaltsas
- Department of Endocrinology and Diabetes CenterG. Gennimatas Hospital, 154 Mesogion Avenue, 11527 Holargos, Athens, Greece andDepartment of PathophysiologyNational University of Athens, Mikras Asias 75, 11527 Athens, Greece
| |
Collapse
|
17
|
|
18
|
Aronova A, III TJF, Zarnegar R. Management of hypertension in primary aldosteronism. World J Cardiol 2014; 6:227-233. [PMID: 24944753 PMCID: PMC4062125 DOI: 10.4330/wjc.v6.i5.227] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
Hypertension causes significant morbidity and mortality worldwide, owing to its deleterious effects on the cardiovascular and renal systems. Primary hyperaldosteronism (PA) is the most common cause of reversible hypertension, affecting 5%-18% of adults with hypertension. PA is estimated to result from bilateral adrenal hyperplasia in two-thirds of patients, and from unilateral aldosterone-secreting adenoma in approximately one-third. Suspected cases are initially screened by measurement of the plasma aldosterone-renin-ratio, and may be confirmed by additional noninvasive tests. Localization of aldostosterone hypersecretion is then determined by computed tomography imaging, and in selective cases with adrenal vein sampling. Solitary adenomas are managed by laparoscopic or robotic resection, while bilateral hyperplasia is treated with mineralocorticoid antagonists. Biochemical cure following adrenalectomy occurs in 99% of patients, and hemodynamic improvement is seen in over 90%, prompting a reduction in quantity of anti-hypertensive medications in most patients. End-organ damage secondary to hypertension and excess aldosterone is significantly improved by both surgical and medical treatment, as manifested by decreased left ventricular hypertrophy, arterial stiffness, and proteinuria, highlighting the importance of proper diagnosis and treatment of primary hyperaldosteronism. Although numerous independent predictors of resolution of hypertension after adrenalectomy for unilateral adenomas have been described, the Aldosteronoma Resolution Score is a validated multifactorial model convenient for use in daily clinical practice.
Collapse
|
19
|
Measurement of plasma renin concentration instead of plasma renin activity decreases the positive aldosterone-to-renin ratio tests in treated patients with essential hypertension. J Hypertens 2014; 32:627-34. [DOI: 10.1097/hjh.0000000000000076] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|