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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Hypertension Canada | OTHER |
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This study is to evaluate the performance characteristics of the seated saline infusion test and the ultra low-dose ACTH stimulation test for the diagnosis of primary aldosteronism.
This is a prospective study (with a target recruitment of 200 participants) designed to evaluate the performance characteristics of the seated saline infusion test and the ultra low-dose ACTH stimulation test for the diagnosis of primary aldosteronism, using disease-specific treatment response as a reference gold standard. Subjects consenting to study participation will undergo a standardized seated saline infusion test, followed by an ultra low-dose ACTH stimulation test. All participants also receive adrenal vein sampling. Individuals who have unilateral disease and desire surgery will receive adrenalectomy (as part of routine care) and the remaining subjects will receive medical treatment with a mineralocorticoid receptor antagonist. Response to targeted treatment will be considered the reference gold standard for the establishing the diagnosis of primary aldosteronism.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Seated intravenous saline infusion test | Diagnostic Test | The test will be conducted by infusing two litres of normal saline intravenously over 4 hours with the patient seated.Blood collection (for aldosterone, cortisol, renin, and electrolytes) will be performed at baseline and after completion of the infusion. Following infusion, plasma aldosterone levels <140 pmol/L will be considered as "negative," levels >280 pmol/L as "positive," and levels in between classified as indeterminate. | ||
| Ultra low-dose ACTH stimulation test | Diagnostic Test | The test will be performed by injecting 0.03 mcg of ACTH intravenously. Blood collection (for aldosterone, cortisol, and renin) will be performed at baseline and after 15 minutes. We expect a "positive" response to correspond with a plasma aldosterone >2200 pmol/L and ARR >220 pmol/L/mIU/L following stimulation. |
| Measure | Description | Time Frame |
|---|---|---|
| Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test) | Measures of diagnostic accuracy, as summarized by receiver operating characteristic curve analyses. | The total study timeline will occur over 66 months. |
| Measure | Description | Time Frame |
|---|---|---|
| The optimal cutoff value for confirmatory testing using clinically-important thresholds | Plasma aldosterone | The total study timeline will occur over 66 months. |
| The optimal cutoff value for confirmatory testing using clinically-important thresholds |
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Inclusion Criteria:
Exclusion Criteria:
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Hypertension individuals suspected of having primary aldosteronism.
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| Name | Affiliation | Role |
|---|---|---|
| Alexander Leung, Asst. Prof | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Calgary | Calgary | Alberta | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27118291 | Background | Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tobe SW, Ruzicka M, Burns KD, Vallee M, Prasad GV, Lebel M, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NR, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Hiremath S, Drouin D, Lavoie KL, Hamet P, Fodor G, Gregoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Harris KC, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; CHEP Guidelines Task Force. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016 May;32(5):569-88. doi: 10.1016/j.cjca.2016.02.066. Epub 2016 Mar 10. | |
| 26934393 |
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| ID | Term |
|---|---|
| D006929 | Hyperaldosteronism |
| ID | Term |
|---|---|
| D000308 | Adrenocortical Hyperfunction |
| D000307 | Adrenal Gland Diseases |
| D004700 | Endocrine System Diseases |
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Aldosterone-to-renin ratio
| The total study timeline will occur over 66 months. |
| Background |
| Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2. |
| 16670162 | Background | Mulatero P, Milan A, Fallo F, Regolisti G, Pizzolo F, Fardella C, Mosso L, Marafetti L, Veglio F, Maccario M. Comparison of confirmatory tests for the diagnosis of primary aldosteronism. J Clin Endocrinol Metab. 2006 Jul;91(7):2618-23. doi: 10.1210/jc.2006-0078. Epub 2006 May 2. |
| 41582811 | Derived | Leung AA, Padwal RS, Hundemer GL, Venos E, Campbell DJT, Holmes DT, Orton DJ, So CB, Przybojewski SJ, Caughlin CE, Pasieka JL, Rabi DM, Kline GA. Seated Saline Suppression Test for Lateralizing Primary Aldosteronism. Hypertension. 2026 May;83(5):e26008. doi: 10.1161/HYPERTENSIONAHA.125.26008. Epub 2026 Jan 26. |
| 40324193 | Derived | Leung AA, Padwal RS, Hundemer GL, Venos E, Campbell DJT, Holmes DT, Orton DJ, So CB, Przybojewski SJ, Caughlin CE, Pasieka JL, Rabi DM, Kline GA. Confirmatory Testing for Primary Aldosteronism : A Study of Diagnostic Test Accuracy. Ann Intern Med. 2025 Jul;178(7):948-956. doi: 10.7326/ANNALS-24-03153. Epub 2025 May 6. |