Emerg Radiol (2015) 22:533538
DOI 10.1007/s10140-015-1327-4
ORIGINAL ARTICLE
Value of the CT Bcapsular sign^ as a potential indicator
of acute adrenal ischemia
Marco Moschetta 1 & Michele Telegrafo 1 & Armando Pignatelli 1 &
Amato Antonio Stabile Ianora 1 & Giuseppe Angelelli 1
Received: 23 January 2015 / Accepted: 20 May 2015 / Published online: 27 May 2015
# American Society of Emergency Radiology 2015
Abstract Acute adrenal ischemia represents a rare cause of
adrenal insufficiency which should be promptly diagnosed in
order to preserve adrenal vitality and function. Our study aims
to retrospectively evaluate the diagnostic accuracy of the CT
capsular sign as an indicator of adrenal ischemia and its asso-
ciation with vascular involvement. Between January 2013 and
January 2014, 69 consecutive patients (47 men, 22 women;
mean age 46; range 2267) with suspected adrenal insufficien-
cy based on clinical and biochemical data underwent 320-row
CT examination in our Emergency Department. Written in-
formed consent was obtained for the CT examinations, and
the institutional review board approval was obtained for our
retrospective study. CT multi-planar images were retrospec-
tively and independently analyzed by two radiologists
searching for the patency of adrenal vessels, enlarged adre-
nals, the presence of the Bcapsular sign^ represented by a
peripheral subtle hyperdense line around a hypodense en-
larged adrenal, and the presence of any periadrenal inflamma-
tory changes. All CT findings were then compared with the
surgical findings (n=5), follow-up examinations (n=20), or
autopsy (n=4). Sensitivity, specificity, diagnostic accuracy
(DA), positive predictive value (PPV), and negative predictive
value (NPV) were calculated for the Bcapsular sign^ and were
further evaluated by ROC analysis. Acute adrenal ischemia
occurred in 29/69 patients (42 %), unilateral in 20, and bilat-
eral in 9. Forty of sixty-nine patients (58 %) had no evidence
of adrenal disease on CT. Thrombosis of the main adrenal vein
* Marco Moschetta
marco.moschetta@gmail.com
1
DIMInterdisciplinary Department of MedicineSection of
Diagnostic Imaging, Aldo Moro University of Bari Medical School,
Piazza Giulio Cesare 11, 70124 Bari, Italy
was found in 20/29 (69 %) and non-venous ischemia in 9/29
(31 %). The capsular sign was found in 24/29 patients (83 %).
Sensitivity, specificity, DA, PPV, and NPV values of 83, 100,
93, 100, and 89 %, respectively, were obtained. The capsular
sign represents a CT indicator of acute adrenal ischemia, with
a specificity of 100 % and leading to a prompt diagnosis in the
early phase of the disease.
Keywords Adrenal . Ischemia . CT . Capsular sign
Introduction
Adrenal insufficiency represents a rare clinical event with an
increasing prevalence. This condition could lead to adrenal
crisis, a life-threatening event requiring immediate glucocor-
ticoid administration and fluid substitution [1, 2].
The most frequent causes of adrenal insufficiency include
autoimmune, infiltrative, and genetic diseases, infections,
bleeding, trauma, surgery, and medications [3].
The clinical signs and symptoms are usually non-specific
and often cause a delay in diagnosis or even misdiagnosis [1].
They include orthostatic hypotension, fever, and abdominal
pain associated with hypoglycemia, hyponatremia,
hyperkalemia, anemia, mild eosinophilia, and lymphocytosis.
Hypercalcemia, increased liver transaminases, and acute renal
failure can also be present [3].
Therefore, the diagnosis of adrenal insufficiency is sug-
gested by non-specific clinical features and confirmed by bio-
chemical testing; however, it could be caused by acute adrenal
ischemia and represents a rare cause of acute abdominal pain.
Therefore, this event should be suspected in all patients pre-
senting with an acute abdominal syndrome with the corre-
sponding clinical and laboratory findings referred to a radio-
logical setting [4]. Rare cases are reported in the literature,
534
mainly associated with pregnancy and/or adrenal/renal vein
thrombosis, including patients with anti-phospholipid anti-
body syndrome [5].
Computed tomography (CT) is the most common imaging
examination performed in patients with acute abdominal pain,
and imaging signs of acute adrenal ischemia, usually
consisting of an enlarged hypodense adrenal without signifi-
cant enhancement after IV contrast material injection, have to
be considered in order to promptly diagnose this condition
[511]. In case of suspected acute adrenal ischemia, the dis-
tinction between non-traumatic adrenal hemorrhage and hy-
povolemic shock needs to be made in order to preserve adre-
nal function by implementing rapid and correct treatment,
although shock can also be a cause of adrenal ischemia and
infarction if not promptly treated [515].
However, to our knowledge, no other specific CT sign of
acute adrenal ischemia has been reported in the medical liter-
ature. We initially anecdotally identified a Bcapsular sign^ on
CT, in patients with adrenal ischemia, and wished to study it
more formally.
The purpose of our study was therefore to evaluate the
diagnostic accuracy of the CT capsular sign represented by a
peripheral subtle hyperdense line around a hypodense en-
larged adrenal, as an indicator of adrenal ischemia and its
association with vascular involvement.
Materials and methods
In the period between January 2013 and January 2014, 69
patients (47 men, 22 women; mean age 46; range 2267)
affected by a non-traumatic acute abdominal syndrome and
suspected of having adrenal insufficiency based on clinical
signs and biochemical tests underwent CT examination in
our Emergency Department. Clinical signs included orthostat-
ic hypotension, fever, and abdominal pain while biochemical
abnormalities included some combination of hypoglycemia,
hyponatremia, hyperkalemia, anemia, mild eosinophilia, lym-
phocytosis, hypercalcemia, and increased liver transaminases.
Written informed consent was obtained for CT examina-
tions. Institutional review board approval was obtained for our
retrospective study.
CT examinations were performed by using a 320-row mul-
tidetector system (Aquilion One, Toshiba Medical Systems,
Otawara, Japan), and the following acquisition parameters
were used: slice thickness 0.5 mm, and increment 0.5 mm,
rotation time 0.5 s; 120/200 kVp/mAs. An automatic dose
modulation system was used in all cases. In all cases, images
were acquired before and after intravenous injection of con-
trast material (Iomeron 400 Bracco, Milan, Italy) in a quantity
equal to 1.5 mL per kg of body weight up to a maximum of
120 mL at a flow rate of 3.5 mL per second. Scans were
performed in the arterial and portal venous phases, with a
Emerg Radiol (2015) 22:533538
mean delay of 3040 and 6070 s, respectively, from the be-
ginning of the contrast administration.
The obtained data were transferred to and analyzed on a
workstation (HP XW 8600) equipped with software dedicated
to image reconstruction (Vitrea FX 2.1, Vital Images,
Minneapolis, MN, USA). Multi-planar (MPR) and maximum
intensity projection (MIP) images were retrospectively and
independently analyzed by two radiologists with 10 years ex-
perience in abdominal CT using image reconstruction soft-
ware, searching for the following parameters based on the
aim of our study:
& Patency of adrenal arterial and venous vessels
& Adrenal morphology and density both on pre- and post-
contrast images
& Adrenal volume (normal values: maximum width perpen-
dicular to the long axis of the adrenal body, 0.7 cm; max-
imum width of the medial limb, 0.3 cm; maximum width
of the lateral limb, 0.3 cm as reported by Vincent et al. in
1994 [16])
& Presence of the Bcapsular sign^ represented by a periph-
eral subtle hyperdense line around an hypodense enlarged
adrenal, based on our preliminary prospective identifica-
tion and then respectively searched for in the examined
patient series
& Presence of peri-adrenal inflammatory changes
All other abdominal vascular structures and organs as well
as perfusion abnormalities were evaluated. The two radiolo-
gists were blinded to the original reports, specific patient his-
tories and final diagnoses. Post-processing time was approxi-
mately 15 min for each CT examination. All CT findings were
then compared with the surgical findings (n=5), CT follow-up
examinations performed within 2 months (n=20) or autopsy
(n=4).
In order to verify the Bcapsular^ sign validity, sensitivity,
specificity, diagnostic accuracy (DA), positive predictive val-
ue (PPV), and negative predictive value (NPV) were calculat-
ed and further evaluated by ROC analysis.
Cohens kappa (k) test was used to evaluate the inter-
observer agreement between the two radiologists and the di-
agnostic reliability of the adrenal capsular sign. A k value of
more than 0.81 was considered to represent near perfect agree-
ment, and values of 0.610.80 and 0.410.60 to represent
substantial and moderate agreement, respectively. All calcula-
tions were performed using NCSS2007 statistical software.
Results
Acute adrenal ischemia occurred in 29/69 patients (42 %)
(Fig. 1), unilateral in 20 (69 %), and bilateral in 9 (31 %).
The main clinical findings were orthostatic hypotension (n=
Emerg Radiol (2015) 22:533538
Fig. 1 Acute adrenal ischemia of the right adrenal in a 36-year-old man.
CT transverse scan in the portal venous phase. The capsular sign (arrow)
consists of an enlarged hypodense adrenal with subtle peripheral rim
enhancement after intravenous contrast material injection caused by
adrenal venous thrombosis
15), fever (n=8), and abdominal pain (n=29), while biochem-
ical disorders included hypoglycemia (n=18), hyponatremia
(n=21), hyperkalemia (n=14), anemia (n=12), mild eosino-
philia (n=6), lymphocytosis (n=22), hypercalcemia (n=14),
and increased liver transaminases (n=22).
The search for anti-phospholipid antibodies was negative
in all patients.
The remaining 40/69 patients (58 %) had no evidence
of adrenal disease on CT. The main clinical signs in-
cluded orthostatic hypotension (n = 11), fever (n = 18),
and abdominal pain (n=40), while biochemical abnor-
malities included hypoglycemia (n = 12), hyponatremia
(n=28), hyperkalemia (n=24), anemia (n=32), mild eo-
sinophilia (n=16), lymphocytosis (n=28), hypercalcemia
(n=21), and increased liver transaminases (n=38), and
18/40 (45 %) of patients were affected by urolithiasis,
12 (30 %) by acute appendicitis, and the reimaging 10
(25 %) were negative for any abdominal disease and
underwent clinical and biochemical follow-up.
With regard to adrenal volume, adrenal enlargement was
identified in all patients affected by adrenal ischemia (n=29),
with an average width perpendicular to the long axis of the
adrenal body of 1.3 cm (standard deviation 0.3), average
width of the medial limb, 0.6 cm (standard deviation 0.2),
and average width of the lateral limb, 0.6 cm (standard devi-
ation 0.3).
In the remaining 40 patients, normal adrenal volume
was found with an average width perpendicular to the
long axis of the adrenal body of 0.6 cm (standard de-
viation 0.2), average width of the medial limb, 0.3 cm
(standard deviation 0.3), and average width of the later-
al limb, 0.2 cm (standard deviation 0.1).
Among the 29 patients with adrenal ischemia, adrenal ve-
nous thrombosis was found in 20/29 (69 %) and non-venous
ischemia in 9/29 (31 %). No periadrenal inflammatory change
was detected. Four patients diagnosed with non-venous
535
adrenal ischemia died because of the onset of disseminated
intravascular coagulation (DIC). The autopsy examination
confirmed the adrenal ischemia in all cases. Five pa-
tients with non-venous adrenal ischemia underwent ad-
renal resection; in three out of five cases, splenic ische-
mia was associated, while in two cases abdominal aortic
aneurysm rupture occurred (Fig. 2). In the remaining 20
patients, the CT diagnosis of venous adrenal ischemia
was established (Fig. 3), and a CT examination after
anticoagulation therapy was performed within 2 months
(Figs. 4 and 5). Two out of 20 patients had undergone
cesarean section within the week before the CT exami-
nation. Complete adrenal reperfusion was obtained in all
cases of venous ischemia, with normal adrenal morphol-
ogy and venous vessel patency.
The CT capsular sign was found in 24/29 patients (83 %).
In particular, the sign occurred in all the 20 patients affected
by venous adrenal ischemia who underwent CT follow-up and
in four out of five patients with non-venous adrenal ischemia
who underwent surgical adrenal removal.
With regard to the CT capsular sign, sensitivity, spec-
ificity, DA, PPV, and NPV values of 83, 100, 93, 100,
and 89 %, respectively, were obtained for diagnosing
adrenal ischemia, as also represented by ROC analysis
(Fig. 6). Near perfect agreement between the two radi-
ologists was found (k=0.87) for the identification of the
CT capsular sign.
Discussion
The adrenal can be affected by different neoplastic and
non-neoplastic pathological conditions. Adrenal ischemia
represents a rare acute disease and an uncommon cause
of acute abdominal syndrome. CT is the preferred cross-
sectional imaging technique for diagnosing adrenal is-
chemia [69].
Magnetic resonance imaging (MRI) can be used to charac-
terize adrenal focal lesions due to its multi-planar and multi-
parametric diagnostic capacity, but it can be performed in the
setting of an acute abdominal syndrome in selected patients
[611].
Therefore, CT can be used to identify volumetric and den-
sitometric changes of the adrenal, especially in such an acute
setting as adrenal ischemia. Usually, adrenal ischemia diagno-
sis is based on the detection of an enlarged hypodense adrenal
on unenhanced CT images without significant enhancement
after IV contrast material injection [511]. Vincent et al. in
1994 established the size of normal adrenal considering the
maximum width perpendicular to the long axis of the adrenal
body and the maximum width of medial and lateral limbs. In
our experience, adrenal enlargement was found in all cases of
536
Fig. 2 Bilateral acute adrenal
ischemia in a 62-year-old man.
Coronal CT image in the portal
venous phase shows the bilateral
adrenal capsular sign and
abdominal aortic dissection
diagnosed as non-venous adrenal
ischemia
acute adrenal ischemia as compared to the threshold values
reported in the medical literature [16].
In addition to the volumetric changes, CT can also be used
to evaluate adrenal vessel patency when acute adrenal ische-
mia is suspected.
Differentiating non-traumatic adrenal hemorrhage
from adrenal ischemia from hypovolemic shock is nec-
essary [1118]. As reported by Kawashima et al. in
1999, adrenal hemorrhage can be caused by stress, co-
agulopathy, and underlying adrenal tumors and is dem-
onstrated as an enlarged gland with high attenuation
values on unenhanced CT scans, ranging from 50 to
90 Hounsfield Units (HU) and with no significant IV
contrast enhancement. Sacerdote et al. in 2012 described
six CT patterns of adrenal hemorrhage: a solid round or
oval mass, solid peripheral components with central flu-
id density, infiltrative appearance, adreniform enlarge-
ment, amorphous solid mass, and active bleeding.
Differential diagnosis could be difficult especially in
cases of solid round or oval mass pattern with a persistent
rim of enhancing normal adrenal tissue. However, high-
density pre-contrast CT scans are useful in order to distinguish
hemorrhage from ischemia [14].
In our CT protocol, unenhanced CT scans were acquired in
all cases due to the emergency setting of the examinations. In
fact, as reported in the medical literature, unenhanced scans
Fig. 3 Acute ischemia of the right adrenal in a 42-year-old man. CT
transverse scan in the portal venous phase shows a thrombus within the
main adrenal vein protruding into the inferior vena cava (a, arrow) and
Emerg Radiol (2015) 22:533538
are useful in cases of acute abdominal syndrome in order to
recognize hematic collections, calcifications, and bowel
perforations.
In contrast, hypovolemic shock is characterized by bilateral
persistent adrenal contrast enhancement without adrenal en-
largement [14]. This could represent a useful criterion for
differential diagnosis with adrenal ischemia.
Besides, in our CT protocol, a triple-phase technique was
used in all cases in order to evaluate the adrenal vessel patency
and the adrenal enhancement for characterizing any focal or
diffuse enlargement of the adrenal.
In fact, this kind of CT protocol allowed to easily differen-
tiate adrenal ischemia which appeared as a hypodense en-
larged adrenal from focal benign or malignant lesions; be-
sides, the portal venous phase provided useful information
regarding the venous etiology of the ischemia, as occurred in
69 % of our cases, and usually it is used to characterize adrenal
lesions based on their enhancement degree as compared with
the unenhanced CT scans.
To our knowledge, few cases of acute adrenal ischemia
have been reported in the medical literature. Fox in 1976 re-
ported 32 cases of venous adrenal infarction; Hoen et al. in
2011 reported two cases of unilateral adrenal ischemia during
the third trimester of pregnancy, and also in our series, two
cases of adrenal ischemia occurred within a week after cesar-
ean section [6, 12].
right adrenal ischemia with the capsular sign (b, arrow). CT image
reconstructed in the coronal plane shows the right adrenal ischemia
with the capsular sign (c, arrow)
Emerg Radiol (2015) 22:533538
Fig. 4 CT transverse (a) and
coronal (b) images in the portal
venous phase show complete
resolution of the right adrenal
ischemia (arrows) after 1 month
of anticoagulation therapy in the
same patient as in Fig. 3
In our retrospective study, 69 patients with adrenal insuffi-
ciency based on clinical and biochemical data have been in-
cluded and only 29 had a CT diagnosis of adrenal ischemia.
Probably, the high number of the suspected cases of adrenal
ischemia in our series was due to a potential bias of searching
adrenal disease among a group of patients with clinical and
biochemical setting of adrenal insufficiency and not in the
general population, as it happens in the clinical practice.
Besides, as a further potential selection bias, we initially
anecdotally identified a capsular sign on CT in patients with
adrenal ischemia, and in order to study it more formally, we
retrospectively searched for this pathological condition in all
patients with adrenal insufficiency.
However, the actual number of the diagnosed adrenal is-
chemia reported in our study is concordant with such other
series reported in the medical literature as the 32 cases de-
scribed by Fox in 1976 [12].
Usually, bilateral adrenal ischemia has been reported in
cases of anti-phospholipid antibody and Waterhouse-
Friderichson Syndromes, while unilateral ischemia has been
associated to V Leiden Factor mutation [6]. In our series,
bilateral ischemia was detected in 69 % of cases while unilat-
eral in 31 %. However, no case of such syndromes occurred in
our series, to our knowledge.
With regard to the CT findings, no other specific sign of
acute adrenal ischemia has been reported in the medical
literature.
Fig. 5 Acute adrenal ischemia of
the right adrenal in a 46-year-old
man. CT coronal images in the
portal venous phase show right
adrenal ischemia with the
capsular sign caused by venous
etiology (a, arrow), and the
subsequent complete resolution
after 2 months of anticoagulation
therapy (b, arrow)
537
In our series, we examined 69 patients suspected of having
adrenal ischemia, and a new CT sign named capsular sign was
detected in the 83 % of the affected patients. The proposed
sign consists of an enlarged hypodense adrenal with a subtle
peripheral rim enhancement after intravenous contrast materi-
al injection, which probably is due to residual perfusion within
the adrenal capsular veins of the ischemic gland. The
sensitivity and diagnostic accuracy of 93 % were found
in our series for the capsular sign. Therefore, based on
our preliminary results, the presence of a capsular sign
correlated to acute ischemia with a 100 % specificity,
and when it was not found, the probability of a non-
ischemic condition was 89 %.
Moreover, we also noticed that this CT feature occurred in
all cases of reversible venous ischemia with a good prognosis
and only in four cases of non-reversible ischemia with no CT
sign of venous thrombosis. Therefore, it could suggest an
early and still reversible phase of ischemia, usually caused
by vein thrombosis and could lead to a prompt therapeutic
approach in order to preserve adrenal vitality especially in
the cases of venous ischemia.
The proposed CT sign could be determined by the main
adrenal vein thrombosis with a patency of the peripheral cap-
sular veins, which allow a residual adrenal rim perfusion. The
associated gland enlargement could be explained by the ede-
ma due to local fluid stasis. Therefore, the capsular sign could
represent an early phase of adrenal ischemia mainly associated
538
Fig. 6 ROC curve as obtained by comparing the CT capsular sign with
the reference standard represented by histological examination after
surgical removal (n=4), autopsy examination (n=5), and CT follow-up
examination within 2 months from diagnosis (n=20)
with venous thrombosis occurring before adrenal hemorrhage
and when the capsular veins are still patent.
Finally, the proposed sign also showed a high reliability as
suggested by the high inter-observer agreement found in our
series. However, further experience is needed to validate our
preliminary data.
Our study has some limitations, primarily the rela-
tively small number of patients, the retrospective nature
of the study, the limited statistical evaluation, the poten-
tial selection bias represented by the inclusion of pa-
tients with clinical and biochemical suspect of adrenal
insufficiency, and the absence of pathologic proof in
most patients and of a clear pathogenesis of non-
venous adrenal ischemia.
In conclusion, the capsular sign, represented by a peripher-
al subtle hyperdense line around a hypodense enlarged adre-
nal, can be a CT indicator of adrenal ischemia. Its presence
correlated with acute ischemia in all cases in our study,
reflecting an early phase of adrenal ischemia and usually cor-
related with reversible venous thrombosis and a good
prognosis.
Emerg Radiol (2015) 22:533538
Conflict of interest All authors have no conflicts of interest nor finan-
cial or personal relationships regarding this paper.
References
1. Hahner S, Allolio B (2005) Management of adrenal insufficiency in
different clinical settings. Expert Opin Pharmacother 6(14):2407
17
2. Brando Neto RA, de Carvalho JF (2014) Diagnosis and classifi-
cation of Addisons disease (autoimmune adrenalitis). Autoimmun
Rev 13(45):40811
3. Quinkler M (2012) Addisons disease. Med Klin Intensivmed
Notfmed 107(6):4549
4. Husebye ES, Allolio B, Arlt W et al (2014) Consensus statement on
the diagnosis, treatment and follow-up of patients with primary
adrenal insufficiency. J Intern Med 275(2):10415
5. Nieman LK (2003) Dynamic evaluation of adrenal hypofunction. J
Endocrinol Invest 26(7 Suppl):7482
6. Hoen N, Ziane G, Grange C, Raudrant D, Dupuis O (2011)
Unilateral adrenal ischemia during third trimester of pregnancy:
about two cases. Gynecol Obstet Fertil 39(5):e736
7. Taylor GA, Me F, Eichelberger MR (1987) Hypovolemic shock in
children: abdominal CT manifestation. Radiology 164:479481
8. Sivit CJ, Taylor GA, Bulas DI, Kushner DC, Potter BM, Eichelberger
MR (1992) Post-traumatic shock in children: CT findings associated
with hemodynamic instability. Radiology 182:723726
9. Shin MS, Berland LL, Kang-Jey H (1990) Small aorta: detection
and clinical significance. J Comput Assist Tomogr 14:102103
10. OHara SM, Donnelly LF (1999) Intense contrast enhancement of
the adrenal gland; another abdominal CT finding associated with
hypoperfusion complex in children. AJR 173:995998
11. Nuutinen P, Kivisaari L, Lehtola A (1986) Hypovolemic shock and
contrast enhanced computed tomography of the pancreas. Scand J
Gastroenterol 21:483486
12. Fox B (1976) Venous infarction of the adrenal glands. J Pathol 119:
6589
13. Sinelnikov AO, Abujudeh HH, Chan D, Novelline RA (2007) CT
manifestations of adrenal trauma: experience with 73 cases. Emerg
Radiol 13:313318
14. Sacerdote MG, Johnson PT, Fishman EK (2012) CT of the adrenal
gland: the many faces of adrenal hemorrhage. Emerg Radiol 19(1):
5360
15. Bollen TL, van Santvoort HC, Besselink MG et al (2007) Intense
adrenal enhancement in patients with acute pancreatitis and early
organ failure. Emerg Radiol 14(5):31722
16. Vincent JM, Morrison ID, Armstrong P, Reznek RH (1994) The
size of normal adrenal glands on computed tomography. Clin
Radiol 49(7):4535
17. Jordan E, Poder L, Courtier J, Sai V, Jung A, Coakley FV (2012)
Imaging of nontraumatic adrenal hemorrhage. AJR 199(1):W918
18. Kawashima A, Sandler CM, Ernst RD et al (1999) Imaging of
nontraumatic hemorrhage of the adrenal gland. Radiographics
19(4):94963