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Section for Endocrine Surgery and Abdominal Sarcoma, Department of Surgery, Institute of Clinical Sciences, and 2 Section for Endocrinology,
Department of Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg,
Sweden
Correspondence to: Professor B. Wngberg, Department of Surgery, Bl Strket 5, 413 45 Gteborg, Sweden (e-mail: bo.wangberg@surgery.gu.se)
Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension. The
main aims of this paper were to review outcome after surgical versus medical treatment of PA and partial
versus total adrenalectomy in patients with PA.
Methods: Relevant medical literature from PubMed, the Cochrane Library and Embase OvidSP from
1985 to June 2014 was reviewed.
Results: Of 2036 records, 43 articles were included in the final analysis. Twenty-one addressed surgical
versus medical treatment of PA, four considered partial versus total adrenalectomy for unilateral PA,
and 18 series reported on surgical outcomes. Owing to the heterogeneity of protocols and reported
outcomes, only a qualitative analysis was performed. In six studies, surgical and medical treatment had
comparable outcomes concerning blood pressure, whereas six showed better outcome after surgery. No
differences were seen in cardiovascular complications, but surgery was associated with the use of fewer
antihypertensive medications after surgery, improved quality of life, and (possibly) lower all-cause mortality compared with medical treatment. Randomized studies indicate a role for partial adrenalectomy in
PA, but the high rate of multiple adenomas or adenoma combined with hyperplasia in localized disease
is disconcerting. Surgery for unilateral dominant PA normalized BP in a mean of 42 (range 2072) per
cent and the biochemical profile in 96100 per cent of patients. The mean complication rate in 1056
patients was 47 per cent.
Conclusion: Recommendations for treatment of PA are hampered by the lack of randomized trials,
but support surgical resection of unilateral disease. Partial adrenalectomy may be an option in selected
patients.
Cutting edge articles are invited by the BJS Editorial Team, and focus on how current research and
innovation will affect future clinical practice.
Paper accepted 11 November 2014
Published online 20 January 2015 in Wiley Online Library (www.bjs.co.uk). DOI: 10.1002/bjs.9744
Introduction
308
Records screened
n = 1351
Records excluded
n = 1283
Full-text articles assessed
for eligibility
n = 68
Full-text articles excluded n = 25
No relevant data n = 16
Outcomes not uniformly reported with regard to
treatment modality n = 7
Overlapping publication n = 2
Studies included in qualitative synthesis n = 43
Surgical versus medical treatment of PA n = 21
Total versus partial adrenalectomy n = 4
Surgical outcomes n = 18
Studies included in
quantitative synthesis
(meta-analysis)
n=0
Fig. 1
PRISMA flow diagram showing selection of articles for review. PA, primary aldosteronism
Methods
Table 1
309
Reference
Location
Design
Miyake et al.18
(2014)
Japan
(multicentre)
Retrospective
Zacharieva
et al.19
(2006)
Sofia, Bulgaria
Prospective
Catena et al.3
(2008)
Udine, Italy
Prospective
Mulatero et al.4
(2013)
Torino, Italy
Reincke et al.20
(2012)
Study
period
Screening/
confirmatory
test/subtype
evaluation
ADX
Medical
treatment
Follow-up
(years)
Main
outcome
variables
Main findings
20032007
n.a.
733
626; type of
treatment n.a.
n.a.
BP and K
A somewhat better
effect on BP and
hypokalaemia for
ADX
n.a.
ARR/none/PT
30
34; all
spironolactone
( 100 mg)
30 ADX; 05
medical
treatment
BP and K
Similar effect on BP
and hypokalaemia
in the two groups
19942001 ARR/SIT/AVS
(26%), NP-59
(87%)
24
31; all
spironolactone
( 100 mg)
74
Cardiovascular
outcome
CHD, cerebrovascular
events and
arrhythmias no
different between
groups
Retrospective
19922009 ARR/SIT/AVS
(33%)
57
213; all
spironolactone
(dose n.a.)
12
Cardiovascular
outcome
CHD, cerebrovascular
events and
arrhythmias no
different between
groups
Germany
(multicentre)
Cross-sectional
157
10
Cardiovascular
outcome
Increased
cardiovascular
mortality in PA;
all-cause mortality
increased in
medical treatment
group
Catena et al.21
(2007)
Udine, Italy
Prospective
24
30; all
spironolactone
( 100 mg)
64
Left ventricular
mass
Rossi et al.22
(2013)
Padua, Italy
Prospective
19922012 ARR/CST/AVS
(100%)
110
30
Left ventricular
mass
Giacchetti et al.23
(2007)
Padua, Italy
Prospective
20032004 ARR/SIT/AVS
(selective)
25
36; 27 MRA
(type and dose
n.a.)
29 ADX; 46
medical
treatment
Left ventricular
mass/glucose
metabolism
Glucose metabolism
improved and left
ventricular mass
decreased in both
groups
Catena et al.24
(2006)
Udine, Italy
Prospective
20
27; all
spironolactone
(50300 mg/day)
57
Glucose
metabolism
Fourkiotis et al.25
(2013)
Germany
(multicentre)
Prospective
86
83; 65
spironolactone
(64 6 mg/day),
18 eplerenone
(88 11 mg/day)
55
Renal function
Iwakura et al.26
(2014)
Sendai, Japan
Prospective
20072010 ARR/CST/AVS
(100%)
102
10 ADX; 07
medical
treatment
Renal function
Prevalence of chronic
kidney disease
increased, GFR and
albumin excretion
decreased to
comparable degree
in the two groups
Reincke et al.27
(2009)
Germany
(multicentre)
Casecontrol
51
63; all
spironolactone
(25150 mg/day)
n.a.
Renal function
Sechi et al.28
(2006)
Udine, Italy
Prospective
19942001 ARR/SIT/AVS
(24%), NP-59
(88%)
22
28; all
spironolactone
(50300 mg/day)
64
Renal function
n.a.
n.a.
ARR/SIT/AVS
(26%), NP-59
(87%)
ARR/SIT/AVS
and/or NP-59
(100%)
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310
Table 1
Continued
Reference
Location
Design
Sechi et al.29
(2009)
Udine, Italy
Prospective
Wu et al.30
(2011)
Taiwan
(multicentre)
Wu et al.31
(2011)
Study
period
n.a.
Screening/
confirmatory
test/subtype
evaluation
ADX
Medical
treatment
Follow-up
(years)
Main
outcome
variables
Main
findings
ARR/SIT/AVS
(22%), NP-59
(87%)
24
30; all
spironolactone
(50300 mg/day)
10
Renal function
Intrarenal vascular
resistance
increased and
urinary protein
losses decreased
similarly in the two
groups
Prospective
63
61; all
spironolactone
(50 mg/day)
10
Renal function
Taiwan
(multicentre)
Prospective
185
101; all
spironolactone
(dose n.a.)
20 ADX; 10
medical
treatment
Renal function
Ahmed et al.32
(2011)
Brisbane,
Australia
Prospective
20092010 ARR/FST/AVS
(100%)
22
21; 12
05
spironolactone
(12525 mg/day)
QoL
Kunzel et al.33
(2012)
Germany
(multicentre)
Prospective
20082009
49
56; 49
43 ADX; 54
spironolactone
medical
(15200 mg/day),
treatment
7 eplerenone
(25150 mg/day)
QoL
Apostolopoulou
et al.34
(2014)
Munich,
Germany
Cross-sectional
20082010 ARR/SIT or
FS/AVS (72%)
49
56; 49
43 ADX; 54
spironolactone
medical
(15200 mg/day),
treatment
7 eplerenone
(25150 mg/day)
Anxiety and
depression
Hanusch et al.35
(2014)
Germany
(multicentre)
Prospective and
cross-sectional
39
57; 39
53
spironolactone
(50240 mg/day),
13 eplerenone
(25200 mg/day)
Sleep
No difference in sleep
quality between the
groups
Kline et al.36
(2013)
Calgary, Canada
Retrospective
20052011 ARR/none/AVS
(96%)
38
Follow-up
time/visits
Follow-up time
shorter and clinical
visits fewer in ADX
n.a.
05 ADX; 11
medical
treatment
ADX, adrenalectomy; n.a., not available; K, potassium; ARR, aldosterone to renin ratio; PT, posture test; SIT, sodium infusion test; AVS, adrenal venous
sampling; NP-59, iodocholesterol scintigraphy; CHD, coronary heart disease; FST, fludrocortisone suppression test; CST, captopril suppression test;
MRA, mineralocorticoid receptor antagonist; PA, primary aldosteronism; OST, oral sodium loading test; GFR, glomerular filtration rate; QoL, quality of
life; FS, furosemide stimulation.
Statistical analysis
Outcome data were categorized (normalized ARR (yes
or no), normalized potassium (yes or no), normalized or
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Table 2
311
Reference
Location
Design
et al.37
Beijing,
China
212
RCT
Fu
(2011)
Nakada
et al.12
(1995)
Yamagata,
Japan
Walz et al.38
(2008)
Essen,
183
Germany
Ishidoya
et al.39
(2005)
Sendai,
Japan
48
92
RCT
Prospective
Screening/
confirmatory
test/subtype
evaluation
ARR/SIT/AVS
selectively
ARR/n.a./AVS
selectively,
NP-59 all
ARR/n.a./AVS
selectively
Retrospective n.a./n.a./AVS
selectively
Procedure
Total ADX
108
Partial ADX
104
Total ADX
22
Partial ADX
26
Hypertension
cured/
Normalized Follow-up
Normalized
K (%)
(years)
Comments
ARR (%) improved (%)
> 05
100
70/30
100
100
72/28
100
n.a.
n.a.
n.a.
n.a.
n.a.
n.a.
Total ADX
136
n.a.
22/63
n.a.
Partial ADX
47
Total ADX
63
n.a.
57/35
n.a.
100
n.a./100
n.a.
24
93
n.a./93
n.a.
52
Partial ADX
29
52
No blinding during
surgery or
follow-up
Details of
randomization not
provided. Similar
improvement with
regard to ARR, K
and hypertension.
Postop. response
to angiotensin II
infusion similar to
that in normal
subjects after
partial ADX,
blunted after total
ADX
49
Operations by 10
surgeons, 69%
multiple lesions in
partial
specimens, 27%
in total ADX
ARR, aldosterone to renin ratio; K, potassium; RCT, randomized clinical trial; SIT, sodium infusion test; AVS, adrenal venous sampling; ADX,
adrenalectomy; n.a., not available; NP-59, iodocholesterol scintigraphy.
Results
Data on surgical versus medical treatment of PA are summarized in Table 1. In six studies, five prospective3,19,22,29,35
and one retrospective36 , the effects on improvement
of BP and hypokalaemia were similar in surgically and
medically treated patients. In another six studies, four
prospective23,25,26,32 and two retrospective4,18 , the effects
on BP and hypokalaemia were better in surgically treated
patients, or they needed fewer antihypertensive drugs.
Reincke and colleagues20 reported reduced all-cause
mortality following adrenalectomy compared with medical
treatment. However, comparing medically and surgically treated patients with PA with regard to coronary
heart disease, cerebrovascular events and arrhythmias,
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312
Table 3
Reference
Screening/
confirmatory
test/subtype
evaluation
Normalized
ARR/K (%)
HT
cured/improved (%)
Mean
follow-up
(years)
n.a./n.a.
55/37
36
11
Mean normal/100
58/42
37
n.a.
n.a./n.a.
n.a.
n.a.
n.a.
ARR/n.a./AVS
selectively
ARR/CST/AVS all
n.a./96
30/57
49
99/n.a.
20/69
008
n.a.
ARR/sARR/AVS
selectively
ARR/SIT + CST/CT
100/n.a.
32/42
06
99/99
54/43
40
156
ARR/sARR/AVS
selectively
96/98
44/56
05
150
ARR/CST SIT/AVS
and NP-59
selectively
ARR/OST/AVS
selectively
ARR/SIT, CST,
FS/AVS and/or
NP-59 all
n.a.
n.a./n.a.
66/33
49
n.a./97
42/46
68
n.a.
100/n.a.
42/56
05
n.a./n.a.
59/41
30
n.a.
Factors predictive
of cure
Zhang et al.40
(2013)
Quillo et al.13
(2011)*
Meria et al.47
(2003)
Lin et al.48
(2007)
Walz et al 38
(2008)
Ishidoya et al.52
(2011)
Letavernier et al.50
(2008)
Jiang et al.51
(2014)
van der Linden
et al.44
(2012)
Wu et al.42
(2009)
376
Lim et al.49
(2014)*
Utsumi et al.45
(2014)
133
Zhang et al.53
( 2009)
Wang et al.43
(2012)
127
124
ARR/SIT/AVS
selectively
n.a./n.a.
55/35
49
Zarnegar et al.41
(2007)
Proye et al.46
(1998)
102
ARR/n.a./AVS
selectively
ARR/n.a./AVS and
NP-59 selectively
n.a./n.a.
39/38
05
100/100
56/44
54
Lumachi et al.55
(2005)
Ip et al.54
(2013)
98
100/100
72/24
67
n.a./n.a.
25/75
008
KCNJ5 mutation
ARR/SIT/AVS
selectively
ARR/OST/AVS
selectively
ARR/n.a./AVS
selectively
n.a.
215
212
195
183
174
168
164
132
100
83
ARR/OST/AVS and
NP-59 selectively
n.a.
*Overlapping series. Cure in 98 per cent defined as normalization of aldosterone and/or BP off all medications. Postoperative aldosterone to renin ratio
(ARR) available for 81 of 168 patients. Postoperative ARR available for 116 patients. Cure in 955 per cent defined as a combination of the
postoperative plasma aldosterone concentration, cure of hypokalaemia, and improvement or cure of hypertension; BP data based on 127 patients. K,
potassium; SIT, sodium infusion test; AVS, adrenal venous sampling; n.a., not available; HT, hypertension; OST, oral sodium loading test; APA,
aldosterone-producing adenoma; CST, captopril suppression test; sARR, supine aldosterone to renin ratio; NP-59, iodocholesterol scintigraphy; BMI,
body mass index; FS, furosemide stimulation.
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314
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13
14
15
16
17
18
19
20
21
22
23
24
315
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Supporting information
Additional supporting information may be found in the online version of this article:
Appendix S1 Search strategies (Word document)
Table S1 Details of outcome of surgery for primary aldosteronism (Word document)
Table S2 Complications after surgery for primary aldosteronism as reported in major case series (Word document)
Fig. S1 Suggested algorithm for diagnosis and treatment of primary aldosteronism (JPEG file)
Snapshot quiz
The answers to the above questions are found on p. 330 of this issue of BJS.
Karavokyros I, Moris D: First Department of Surgery, Laikon General Hospital, Athens 11527, Greece (dimmoris@yahoo.com)
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