Vol.1, No.4, 269-273 (200
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9) Health
Aldosteronoma causing Conn’s syndrome:
a case report and literature review
Hsin-Hui Shao1, Hock-Liew Eng2, Wen-Sheng Huang3, Joseph Nybo Lin4
1Department of Family Medicine, Mackay Memorial Hospital, Hsinchu Branch, Taiwan, China
2Department of Path o l o gy, Chang Gung Memorial Hospital, Taiwan, China
3Department of Nuclear Medicine, Tri-Service General Hospital, Taiwan, China
4Johns Hopkins University, Sc hool of Public Health, Baltimore, Maryland, USA; josephsimion@hotmail.com
Received 17 November 2009; revised 28 November 2009; accepted 29 November 2009.
We report a case of primary aldosteronism
caused by bilateral solitary aldosteronomas
occurring 6 months apart, the diagnosis being
confirmed by clinical features. Multiple aldos-
terone-pr oduc ing ade nom as can be u nilater al or
bilateral. If bilateral, most of them are found
simultaneously. Bilateral solitary aldosterono-
mas occurring at separate times are rarely re-
ported and the pathogenesis is still elusive. We
believe, from this case, the postoperative fol-
low-up in patients with primary aldosteronism is
Keywords: Adrenal Tumor; Aldosteronism; Bilateral
Aldosterone-Producing Adenomas; Aldosteronoma;
The most frequent causes of mineralocorticoid hyperten-
sion are primary hyperaldosteronism (Conn’s syndrome)
due to a solitary aldosterone-producing adenoma (APA)
and bilateral hyperplasia aldosteronism (BHA). Surgery
is the treatment of choice for APA [1,2], but not for BHA
[3 ]. Co rr ect manage ment depen ds o n the physi cia ns ’ ability
to tell the difference between these two diseases, and
several methods have been devised to aid this distinction
[4]. We report a rare case of bilateral solitary adrenocor-
tical adenomas causing primary hyperaldosteronism at
separate periods 6 months apart, the diagnosis confirmed
by clinical features, operation, and pathology.
The subject, a 40-year-old woman in 2000, visited our
endocrine outpatient clinic with the main complaint of
recurrent hypertension for four years after left total
adrenectomy about five years ago.
According to her past medical history, hypertension
(systolic BP 190 mmHg, diastolic BP 110 mmHg) and
hypokalemia (2.5 meq/l) were first recorded at a regional
tertiary hospital in 1995 . A morn ing ambulatory test was
done under the suspicion of hyperaldosteronism. Plasma
cortisol concentration, 17.2 ug/ml at 08:00 h (normal:
9-23 ug/dl) and 1.7 ug/ml at midnight, showed a normal
circadian drop throughout the test. Upright plasma al-
dosterone level was 703 pg/ml (normal: 40-310 pg/ml) at
08:00 h, and it decreased slightly after four hours of
walking (652 pg/ml). And the upright plasma aldoster-
one/plasma renin activity ratio was greater than 30.
Plasma renin level was still suppressed throughout the
test (data not shown). Abdomen computerized tomogra-
phy (CT) revealed a 1x1.5 cm hypodense mass over the
left adrenal gland (Figure 1), and controlateral adrenal
appearance was normal at CT scan. Adrenal vein sam-
pling analyses showed that the aldosterone level from the
left adrenal vein (743 pg/ml) greatly exceeded that from
the right adrenal vein (131 pg/ml). The diagnosis of pri-
mary aldosteronism due to an aldosterone-producing ade-
noma of the left adrenal gland was therefore confirm ed.
Figure 1. Abdomen CT with enhancement revealed a tumor in
left adrenal gland (black arrow).
H. H. Shao et al. / HEALTH 1 (2009) 269-273
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(a) (b) (c)
Abbreviations: (C) capsule, (G) zone glomerulosa, (F) zone fasciculata, (R) zone reticularis, (M) medulla, (A) adenoma.
Figure 2. (a) Normal part of left adrenal gland (H&E, x40); (b) A part of adenoma and adjacent normal tissue in left adrenal gland
(H&E, x40); (c) A part of adenoma of left adrenal gland (H&E, x100). Cells were large, clustered, and clear-lipid filled.
(a) (b)
Figure 3. (a) Abdomen CT with enhancement in June 1999 and (b) follow-up abdomen MRI in March 2002 both revealed a tu-
mor in right adrenal gland (black arr ows) and left adren al was absent.
(a) (b)
Figure 4. A part of adenoma. Right adrenal gland. (a) H&E, x40; (b) H&E, x100.
The patient underwent left side total adrenectomy in
May 1996. The pathology report showed a well-encap-
sulated nodule measuring 1.4x1.7x1.2 cm, composed mainly
of clear cells in cords and clusters, and the diagnosis of
adrenal cortical adenoma was favored. There was no
hyperplastic change or other adenoma noted in the adja-
H. H. Shao et al. / HEALTH 1 (2009) 269-273
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cent adrenal cortical tissue (Figure 2). One week after
operation, the serum potassium (K) level returned to
normal range (4.3 meq/l), and the sequential measurement
of her plasma aldosterone 43 pg/ml and plasma renin
10.1 uU/ml (normal: 7 to 76 uU/ml) revealed within nor-
mal limits.
Thereafter, her blood pressure (systolic BP 105-110
mmHg, diastolic BP 65-80 mmHg) and serum potassium
level (3.6-4.3 meq/l) remained normal after operation
without any medication. However, recurrence of hyper-
tension and hypokalemia developed after half a year, and
she was treated with amlodipine 5 mg once daily regu-
larly and potassium chloride tablet when needed. Her
blood press ure wa s not wel l c on trolled by the medicati on ,
and follow-up abdomen CT in June 1999 revealed a
small nodule about 1x1 cm over the right adrenal gland
(Figure 3(a)). She was then referred to our endocrine
clinic for further management in July 2000.
Physical examination revealed hypertension (168/109
mmHg) and tachycardia (108/min); the other findings
were unremarkable. There was no contributory family his-
tory of hypertensive disease. Laboratory data under am-
lodipine and potassium chloride treatment showed serum
sodium (Na) level of 142 meq/l (normal: 135-145 meq/l),
K 2.1 meq/l (normal: 3.6-4.8 meq/l), creatinine 0.6 mg/dl
(normal: 0.4-1.4 mg/dl), 08:00 h cortisol 10.1 ug/ml
(normal : 9-23 ug/dl), 08: 0 0 h ACTH 96.7 pg/ml (normal:
9-52 pg/ml), upright aldosterone 689 pg/ml (normal:
29-162 pg/ml), and the upright plasma aldostero ne/ pla sma
renin activity ratio was greater than 30. 24 hr urinary
vanillylmandelic acid excretion was normal. Recurrent
primary hyperaldosteronism was highly suspected. After
withdrawal of amlodipine and potassium chloride tablet,
131I-6-beta-iodomethyl-norcholesterol (NP-59) adrenal
scintiphotographic study under dexamethasone suppres-
sion (1 mg four times a day) revealed early visualization
of the right adrenal gland, suggesting hyperfunction of
the remaining right adrenal gland. Repeated laboratory
data during the examination of adrenal scintiphotogra-
phy showed Na 141 meq/l, K 2.7 meq/l, and aldosterone
567 pg/ml. Plasma renin level was also low throughout
the test (data not shown). Other endocrine hormone an aly -
ses remained within normal limits including prolactin
22.6 ng/ml, growth hormone 0.05 ng/ml, intact parathy-
roid hormone (iPTH) 7.2 pg/ml, fasting insulin 5.1 uI U/ml,
gastrin 49.1 pg/ml, calcitonine 2.3 pg/ml, and carcinoem-
bryonic anti ge n (C EA ) 1.8 pg/ml .
The patient was then placed on captopril 25mg twice
daily and spironolactone 50mg twice daily in December
2000. The following treatment course was smooth, and
her blood pressu re and serum K level returned to normal
range (systolic BP 110-120 mmHg, diastolic BP 70-80
mmHg, and K 3.5-4.1 meq/l) with regular medication
until March 2002, when higher blood pressure (systolic
BP 134-147 mmHg, diastolic BP 90-110 mmHg) re-
curred, and she began to feel fatigue again. Abdomen
magnetic resonance imaging (MRI) revealed a 1.5x1.2
cm mass over the right adrenal gland (Figure 3(b)), so
she underwent right retrop eritoneoscopic adrenal tumor
resection (partial adrenectomy) in April 2002. The pa-
thology report showed a cm mass com-
posed of nests of large lipid-rich cells and some lipid-
poor cells, and the diagnosis of adrenal cortical ade-
noma was favored (Figure 4).
Three days after operation, her aldosterone level was
below 25 pg/ml. Since the patient’s discharge, her blood
pressure and potassium level have remained normal
(systolic BP 90-120 mmHg, diastolic BP 60-80 mmHg,
K 4.0-4.3 meq/l) for more than one year without any
medication. Her plasma cortisol level has been within
normal limits after operation. Other endocrine hormone
analyses, including prolactin, growth hormone, iPTH,
fasting insulin, gastrin, calcitonine, and CEA, have re-
mained within normal limits throughout the course.
The primary function of aldosterone is regulation of ex-
tracellular volume and control of potassium homeostasis
[5]. Primary hyperaldosteronism, the cause of approxi-
mately 0.05% to 2.2% of all secondary hypertension, is
characterized by suppressed plasma renin activity and
hypokalemia [1]. Recognized etiologies include unilat-
eral APA, BHA, adrenocortical carcinoma, and glucocor-
ticoid-remediable aldosteronism (GRA). Solitary APA is
the most common cause of primary aldosteronism and
accounts for approximately 65% of cases; BHA accounts
for 30% to 35% and GRA fewer than 3% [6]. Bilateral
solitary aldosteronomas occurring separately and causing
primary hyperaldosteronism are rarely reported. From
literature, simultaneous presence of unilateral multiple
APA [7,8], a hyperfunctioning aldosteronoma with a
minimally functioning adenoma on the other side [9],
or simultaneous bilateral functioning aldosteronomas
[10] have been described. Furthermore, recurrence of
APA in the same adrenal gland [11] 9 years apart has
also been mentioned. The incidence of multiple APA
va rie d f r om 3.9 % to 10 % according to different reports
[7,8,12], suggesting the real incidence may be higher
than we expected.
The clinical pictures of our case were not very differ-
ent from a typical unilateral APA before her first opera-
tion. First, morning ambulation has been used to evalu-
ate the suppression of aldosterone by monitoring plasma
cortisol and aldosterone to upright ambulation [13]. In
patients with APA, aldosterone levels generally decline
in parallel with circadian secretion of cortisol [14]. In
contrast, in patients with BHA, there is usually an in-
crease in renin and aldosterone levels in response to up-
right posture. In our case, plasma cortisol concentration
showed a normal circadian drop throughout th e test. The
H. H. Shao et al. / HEALTH 1 (2009) 269-273
SciRes Copyright © 2009 Openly accessible at http://www.scirp.org/journal/HEALTH/
plasma aldosterone level was much higher at 08:00 h,
and had decreased slightly after four hours of walking.
Plasma renin level was suppressed throughout the test.
Image study for the differential diagnosis of a unilateral
adenoma or bilateral hyperplasia includes a CT scan or
MRI. The sensitivity of CT to distinguish solitary APA
and BHA has been reported at 85% [15] or higher [16].
In our case, the CT image in 1995 revealed a we ll -d ef i ne d
mass over the right adrenal gland and normal appearance
of the left adrenal gland. However, if the CT scan or
MRI is normal, or if bilateral nodular hyperplasia cannot
be ruled out, adrenal vein aldosterone sampling may be
considered as a next step. Adrenal vein sampling, having
the value of physiologic localization, has been one of the
first tests used to distinguish between APA and BHA
[17]. The aldosterone level from the left adrenal vein
was five times greater than that from the right adrenal
vein in our case. This result was compatible with the key
diagnostic feature of unilateral adenoma, which requires
a unilateral two to threefold elevation of aldosterone [18].
However, there was no further scintiphotography per-
formed in 1995 to evaluate the functional status of the
other adrenal gland.
In 1999, CT image in our case showed another
well-defined mass over the right adrenal gland. The
patient’s left adrenal had already been removed. What
we needed to do was to confirm the hyperfunctional
state of her remaining right adrenal gland, and it was
proved by the NP-59 adrenal scintiscan. NP-59 scintis-
can has been reported as a unique imaging technique
because it can depict the functional status of the ad-
renals in syndromes with hypersecretion of glucocor-
ticoid, mineralcorticoid or androgen hormones [19].
The diagnostic sensitivity of the NP-59 adrenal scintis-
can in the localization of aldosteronomas with ade-
quate dexamethasone suppression may be more than
80% to 97% [20-22].
Glucocorticoid-remediable aldosteronism (GRA) is
another rare form of hyperaldosteronism [23]. GRA is
usually associated with bilateral adrenal hyperplasia,
the plasma potassium concentration is normal in more
than half of all cases of GRA. The circadian rhythm of
aldosterone release in GRA is primary under the influ-
ence of ACTH release. Therefore, in our practice, we
used dexamethasone suppression test [24] to rule out
the possibility of GRA during the adrenalscintiphoto-
graphic study.
Surgical treatment is very effective in cases due to
APA [25], whereas surgery in BHA is seldom curative
[12]. Early normalization of blood pressure [7] and
potassium level [26] has been reported in the postop-
erative course of APA. Normalization may take up to
one month but is usually achieved within one week
after surgery. In our case, the patient’s laboratory data
improved within one week of operation, and she was
symptom-free without any medication after surgery for
at least half a year, suggesting that BHA is unlikely.
More importantly, three experienced pathologists con-
firmed that the normal adrenal tissue surrounding the
adenoma showed no hyperplasic changes, which is
present in typ ical BHA.
The underlying pathogenesis of bilateral solitary al-
dosteronoma occurring six months apart in our case is
still unknown, although we have formed several hypothe-
ses. First of all, it was possible that there was coexis-
tence of bilateral adenomas initially. The left adrenal
adenoma was well differentiated and secreted excess
aldosterone, while the right adrenal adenoma remained
in the stage of cell proliferation without hypersecretion.
This phenomenon has been observed in a patient with
ACTH-independent Cushing’s syndrome [27]. It is
therefore possible in our case that the right adrenal ade-
noma became autonomous and progressively enlarged
after removal of the left adrenal adenoma. Since we did
not perform functional scintiscan of the bilateral adrenal
glands before the first operation, there was no sufficient
data to support this hypothesis. Secondly, benign enlarge-
ment of the adrenal cortex has been found in about one
third of the cases of multiple endocrine neoplasia type 1
(MEN 1), and rarely an aldosterone-producing adenoma
has been described [28,29]. However, the other endo-
crine hormone analyses in our case, including plasma
parathyroid hormone, gastrin, insulin, or prolactin, re-
mained within normal limits, so early presentation of
MEN 1 was not likely at present. Thirdly, bilateral al-
dosteronoma secondary to long-term hyperreninemia has
been reported [30]. However, plasma renin level in our
case was low throughout the course, and there was no
evidence of renal artery stenosis or renal ischaemia in
our case. Finally, an increased prevalence of adrenal
lesions in patients with familial adenomatous polyposis
(FAP) has been reported [31]. Most of these lesions are
nonfunctioning adenomas, and some patients have hy-
percortisolism. A sporadic case of FAP with mineralo-
corticoid excess due to APA also has been reported [32].
In our case, there was no contributory family history of
hypertensive disease, and her occult blood test of routine
stool exam was negative.
In summary, although unilateral solitary APA is the
most common cause of primary aldosteronism, multi-
ple or bilateral hyperfunctioning adenomas may be
more frequent than previously thought. Postoperative
follow- up in patients with primary aldosteronism is
worth our attention. Long-term monitoring of blood
pressure and serum potassium level in these patients is
H. H. Shao et al. / HEALTH 1 (2009) 269-273
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