Predicting Reduction of Hypertension After Adrenalectomy for Primary Aldosteronism: a Multicenter Analysis

Characteristics Predicting Clinically Relevant Reduction of Hypertension Following Adrenalectomy for Primary Aldosteronism: a Multicenter Analysis

Primary aldosteronism (PA) is the excessive endogenous production of the mineralocorticoid aldosterone. Although various rare forms of PA exist, the vast majority of cases are accounted by either an aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. During the last decades the prevalence of PA has risen, predominantly due to better awareness of disease. Several studies estimated a prevalence of PA up to 17% in an unselected population of hypertensive patients. However, in a population with resistant hypertension the reported prevalence is even higher: 17-23%. This emphasizes the clinical impact of PA on morbidity and mortality due to high blood pressure. Since both hypertension and aldosteronism are independent risk factors for cardiovascular morbidity, the aim of treatment is curation or reduction of both.

After an adrenalectomy for APA normalization of biochemical abnormalities is achieved in almost all cases. Nevertheless, curation of hypertension (systolic blood pressure <140 and diastolic blood pressure <90 mmHg) without the need of antihypertensive medication is accomplished in only 35-45% of the cases. In 2008 the Aldosteronoma Resolution Score (ARS) was developed. This score predicts the likelihood of complete resolution of the hypertension in patients with an aldosteronoma and has been validated by other investigator groups.

Reduction of hypertension is also an important clinical outcome and is reported in 90-98% of the patients after surgery. In most studies reduction is defined as a certain decrease in blood pressure or antihypertensive medication. However, there is no consensus on the precise definition of reduction in these patients, which leads to incomparable results.

The aim of the proposed study is to determine the proportion of patients with clinically relevant reduction of hypertension after adrenalectomy in a large cohort. Furthermore, the investigators aim to determine the characteristics predicting this clinically relevant reduction. Additionally, the investigators evaluate the predictive value of the Aldosteronoma Resolution Score for clinically relevant reduction and aim to develop a scoring system to help clinicians predict the likelihood of reduction of hypertension after adrenalectomy so it can be used for patient counseling.

Study Overview

• Status: Completed
• Conditions: Primary Aldosteronism; Primary Aldosteronism Due to Aldosterone Producing Adenoma; Primary Aldosteronism Due to Conn Adenoma
• Intervention / Treatment: Procedure: Unilateral adrenalectomy

• Study Type: Observational
• Enrollment (Actual): 514

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • University of Sydney
• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • University Health Network Toronto
  • Quebec
    • Montréal, Quebec, Canada
      • Montreal General Hospital - McGill University
• Italy
  • Lazio
    • Rome, Lazio, Italy
      • Istituto di Semeiotica Chirurgica Roma
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
  • Limburg
    • Maastricht, Limburg, Netherlands
      • Maastricht University Medical Center
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands
      • Amsterdam University Medical Center
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Primary aldosteronism patients who underwent unilateral adrenalectomy between 2010 and 2016 for APA

Description

Inclusion Criteria:

• All patients who underwent unilateral adrenalectomy between 2010 and 2016 for APA.
• Patients with biochemical evidence of primary aldosteronism who underwent adrenalectomy on account of an aldosterone-producing adenoma(APA), proven by Computerized Tomography(CT) or Magnetic Resonance Imaging(MRI) or Adrenal Venous Sampling(AVS).

Exclusion Criteria:

• Age <18 years.
• Missing or incomplete data about preoperative blood pressure and number of antihypertensive drugs.
• Missing or incomplete follow-up data about postoperative blood pressure and number of antihypertensive drugs. We aim enter the blood pressure and number of antihypertensive drugs closest to 6 months after adrenalectomy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

16

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
University Medical Center Utrecht; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
University Medical Center Groningen; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Vu University Medical Center Amsterdam; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
University Medical Center Maastricht; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Academic Medical Center Amsterdam; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Istituto di Semeiotica Chirurgica Roma; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
University of California San Francisco; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Northwestern Memorial Hospital; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Weill Cornell Medical Center; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Columbia University Medical Center; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
University of Chicago Medical Center; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
M.D. Anderson Cancer Center; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Boston Medical Center; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
University Health Network Toronto; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
Montreal General Hospital - McGill University; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy
University of Sydney; Patients who underwent adrenalectomy for primary aldosteronism in case of an aldosterone-producing-adenoma	Procedure: Unilateral adrenalectomy; Other Names: Endoscopic posterior adrenalectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative blood pressure measurement	systolic and diastolic blood pressure via office blood pressure measurements	6 months postoperative
antihypertensive medication use	number of antihypertensives in defined daily dose	6 months postoperative (corresponding to the entered postoperative blood pressure)
resolution of hypertension	resolution of hypertension score via the PASO consensus criteria	6 months postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative serum potassium level	Serum potassium in mmol/l.	6 months postoperative
Postoperative plasma aldosterone level in lying and standing position	Plasma aldosterone in nmol/l.	6 months postoperative
Postoperative plasma renin activity in lying and standing position	Plasma renin activity in mg/L/u.	6 months postoperative
Postoperative aldosterone to renin ratio	Aldosterone to renin ratio using plasma aldosterone level and plasma renin activity	6 months postoperative
Postoperative plasma creatinine level	Plasma creatinine in mg/dL	6 months postoperative
Pathology	Final result of pathology after adrenalectomy	6 months postoperative

Collaborators and Investigators

• Sponsor: UMC Utrecht
• Collaborators: M.D. Anderson Cancer Center; University Health Network, Toronto; University of Chicago; Columbia University; University Medical Center Groningen; Maastricht University Medical Center; Weill Medical College of Cornell University; Boston Medical Center; University of California, San Francisco; Catholic University of the Sacred Heart; Amsterdam UMC, location VUmc; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); University of Sydney; Northwestern Memorial Hospital; Montreal General Hospital
• Investigators: Principal Investigator: Menno R Vriens, MD, UMC Utrecht; Study Director: Gerlof D Valk, MD, UMC Utrecht

Publications and helpful links

General Publications

• Williams TA, Lenders JWM, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young WF Jr, Gomez-Sanchez CE, Funder JW, Reincke M; Primary Aldosteronism Surgery Outcome (PASO) investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 2017 Sep;5(9):689-699. doi: 10.1016/S2213-8587(17)30135-3. Epub 2017 May 30.
• Zarnegar R, Young WF Jr, Lee J, Sweet MP, Kebebew E, Farley DR, Thompson GB, Grant CS, Clark OH, Duh QY. The aldosteronoma resolution score: predicting complete resolution of hypertension after adrenalectomy for aldosteronoma. Ann Surg. 2008 Mar;247(3):511-8. doi: 10.1097/SLA.0b013e318165c075.
• Utsumi T, Kawamura K, Imamoto T, Kamiya N, Komiya A, Suzuki S, Nagano H, Tanaka T, Nihei N, Naya Y, Suzuki H, Tatsuno I, Ichikawa T. High predictive accuracy of Aldosteronoma Resolution Score in Japanese patients with aldosterone-producing adenoma. Surgery. 2012 Mar;151(3):437-43. doi: 10.1016/j.surg.2011.08.001. Epub 2011 Oct 13.
• Aronova A, Gordon BL, Finnerty BM, Zarnegar R, Fahey TJ 3rd. Aldosteronoma resolution score predicts long-term resolution of hypertension. Surgery. 2014 Dec;156(6):1387-92; discussion 1392-3. doi: 10.1016/j.surg.2014.08.019. Epub 2014 Nov 11.
• Stowasser M, Gordon RD, Gunasekera TG, Cowley DC, Ward G, Archibald C, Smithers BM. High rate of detection of primary aldosteronism, including surgically treatable forms, after 'non-selective' screening of hypertensive patients. J Hypertens. 2003 Nov;21(11):2149-57. doi: 10.1097/00004872-200311000-00025.
• Vorselaars WMCM, Nell S, Postma EL, Zarnegar R, Drake FT, Duh QY, Talutis SD, McAneny DB, McManus C, Lee JA, Grant SB, Grogan RH, Romero Arenas MA, Perrier ND, Peipert BJ, Mongelli MN, Castelino T, Mitmaker EJ, Parente DN, Pasternak JD, Engelsman AF, Sywak M, D'Amato G, Raffaelli M, Schuermans V, Bouvy ND, Eker HH, Bonjer HJ, Vaarzon Morel NM, Nieveen van Dijkum EJM, Vrielink OM, Kruijff S, Spiering W, Borel Rinkes IHM, Valk GD, Vriens MR; International CONNsortium study group. Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism. JAMA Surg. 2019 Apr 1;154(4):e185842. doi: 10.1001/jamasurg.2018.5842. Epub 2019 Apr 17.
• Vorselaars WMCM, van Beek DJ, Postma EL, Spiering W, Borel Rinkes IHM, Valk GD, Vriens MR; International CONNsortium study group. Clinical outcomes after surgery for primary aldosteronism: Evaluation of the PASO-investigators' consensus criteria within a worldwide cohort of patients. Surgery. 2019 Jul;166(1):61-68. doi: 10.1016/j.surg.2019.01.031. Epub 2019 May 1.
• Vorselaars WMCM, van Beek DJ, Postma EL, Spiering W, Borel Rinkes IHM, Valk GD, Vriens MR; International CONNsortium Study Group. Validation of the Aldosteronoma Resolution Score Within Current Clinical Practice. World J Surg. 2019 Oct;43(10):2459-2468. doi: 10.1007/s00268-019-05074-z. Erratum In: World J Surg. 2019 Sep 5;:
• Vorselaars WMCM, van Beek DJ, Suurd DPD, Postma E, Spiering W, Borel Rinkes IHM, Valk GD, Vriens MR; International CONNsortium*. Adrenalectomy for Primary Aldosteronism: Significant Variability in Work-Up Strategies and Low Guideline Adherence in Worldwide Daily Clinical Practice. World J Surg. 2020 Jun;44(6):1905-1915. doi: 10.1007/s00268-020-05408-2.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2016
• Primary Completion (Actual): March 26, 2017
• Study Completion (Actual): March 26, 2017

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Actual): February 18, 2021
• Last Update Submitted That Met QC Criteria: February 17, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Blood Pressure; Hyperaldosteronism; Primary Aldosteronism; Adrenalectomy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Adrenal Cortex Diseases; Hypertension; Adenoma; Hyperaldosteronism; Adrenocortical Adenoma
• Other Study ID Numbers: 16-196/C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No