Characteristics Predicting Clinically Relevant Reduction of Hypertension Following Adrenalectomy for Primary Aldosteronism: a Multicenter Analysis
Conditions: Primary Aldosteronism Due to Aldosterone Producing Adenoma, Primary Aldosteronism, Primary Aldosteronism Due to Conn Adenoma
Sponsor: UMC Utrecht

Study Protocol  
Characteristics Predicting Clinically Relevant Reduction of 
Hypertension Following Adrenalectomy for Primary 
Aldosteronism: a Multicenter Analysis 
 
 
 
 
University Medical Center Utrecht, Cancer Center,  
The Netherlands 
Division of Surgical Oncology and Endocrine Surgery 
 
W.M.C.M. Vorselaars, MSc Student 
 
 
 
 
 
05-04-2016 
w.m.vorselaars@umcutrecht.nl 
 
M.R. Vriens, MD PhD, Prof. Endocrine Surgery 
mvriens@umcutrecht.nl 
 

Background 
Primary aldosteronism (PA) is the excessive endogenous production of the 
mineralocorticoid aldosterone1. 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, also described as idiopathic hyperaldosteronism (IHA)2, 3. 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 pressure4-7. Since both hypertension and 
aldosteronism are independent risk factors for cardiovascular morbidity, the aim of 
treatment is curation or reduction of both8.     
After an adrenalectomy for APA normalization of biochemical abnormalities is achieved in 
almost all cases. Nevertheless, curation of hypertension (SBP <140 and DBP <90 mmHg) 
without the need of antihypertensive medication is accomplished in only 35-45% of the 
cases9-11. In 2008 Zarnegar et al. developed the Aldosteronoma Resolution Score (ARS). 
This score predicts the likelihood of complete resolution of the hypertension in patients 
with an aldosteronoma and has been validated by others9-11. 
Reduction of hypertension is also an important clinical outcome and is reported in 90-98% 
of the patients after surgery9-11. 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. Up 
until now only one study has analyzed the characteristics predicting clinically relevant 
reduction of hypertension12. In a study by Worht et al. reduction was defined as: reduction 
of the number of antihypertensive drugs ≥ 33% with a systolic blood pressure ≤ 130mm 
Hg. They showed reduction in 72% of the cases(n=58). Preoperative systolic blood 
pressure and serum creatinine were significantly higher in patients showing no reduction 
of hypertension.  
 
 
 
 
 
 

Objectives 
Although complete resolution of hypertension is the primary goal of unilateral 
adrenalectomy, reduction of hypertension leads to a lifelong decrease of cardiovascular 
morbidity and mortality. Moreover, reduction of hypertension can lead to decrease of 
antihypertensive medication and thereby improve the quality of life of the patient. 
Therefore, reduction of hypertension is also a favorable result of adrenalectomy. 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, we aim to 
determine the characteristics predicting this clinically relevant reduction. Additionally, we 
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.    
 
Definitions/Outcome measures  
To evaluate differences between those patients who were cured versus who had reduction 
versus who had no reduction, patients will be stratified based on clinical response to 
adrenalectomy. Definitions are based on both American and European guidelines for the 
management of hypertension13, 14.  
Patients who were completely off antihypertensive drugs and had a postoperative systolic 
blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg are considered as 
‘’resolution of hypertension’’.  
‘’reduction of hypertension’’ is defined as: a decrease in the number of antihypertensive 
drugs for preoperative normotensive patients (SBP < 140 and DBP < 90 mm Hg) or a 
decrease of postoperative blood pressure (SBP < 140 and DBP < 90 mm Hg) with the same 
or less number of antihypertensive drugs for patients with preoperative resistant 
hypertension.  
Patients who are not meeting these endpoints are stratified as ‘’no reduction of 
hypertension’’. 
 
Research Design 
An international multicenter retrospective cohort study.  
 

 
Inclusion Criteria 
1. 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). 
2. Operated between 2010-2016 in your institution.  
 
Exclusion Criteria 
1. Missing or incomplete data about preoperative blood pressure and number of 
antihypertensive drugs. 
2. 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 Variables  
Patients demographics and preoperative disease characteristics will be queried, including 
age at time of operation, gender, history of cardiovascular events, BMI, mean preoperative 
systolic and diastolic blood pressure, preoperative number of antihypertensive drugs, 
duration of hypertension, family history of hypertension, smoking, hypercholesterolemia, 
diabetes and possible supplementation of potassium. The ARS will be calculated for each 
patient. Furthermore, results of imaging and AVS will be collected. Laboratory data 
collected include serum aldosterone, potassium and creatinine levels and plasma renin 
activity. The aldosterone to renin ratio will be calculated. Also operative characteristics 
(i.e., approach and tumor laterality) and pathologic diagnosis (i.e., aldosteronoma or 
hyperplasia and tumor size) will be reported.  
 
Study Outcomes 
The primary outcomes of this study are the postoperative mean systolic and diastolic blood 
pressure and the number of antihypertensive drugs. Secondary outcomes are 
postoperative serum aldosterone and potassium levels. Both primary and secondary 
outcomes will be measured at approximately 6 months after adrenalectomy(range 3-9 
months). 
 

Statistical analysis 
To determine characteristics predicting clinically relevant reduction univariate analysis 
will be conducted with Pearson’s chi-square test and Mann-Whitney U test. A P value of < 
0.05 will be considered statistically significant. Binary logistic regression modeling will be 
carried out on variables demonstrating statistical significance in univariate analysis. A P 
value of < 0.05 will be considered statistically significant. The predictive accuracy of the 
ARS for reduction of hypertension will be reported as the proportion of patients with 
reduction in each likelihood level of the ARS: low (ARS 0-1), medium (ARS 2-3), high (ARS 
4-5). When possible a new prediction model for reduction of hypertension after 
adrenalectomy will be developed by analyzing the receiver operator characteristics to 
determine the area under the curve.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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