AJR 2004; 183:220-222
© American Roentgen Ray Society
Sequential Adrenal Infarction Without MRI-Detectable Hemorrhage in Primary Antiphospholipid-Antibody Syndrome
A. M. Riddell1 and
K. Khalili
1 Both authors: Department of Medical Imaging, Toronto General Hospital,
University Health Network, 200 Elizabeth St., Toronto, ON M5G 2C4,
Canada.
Received August 26, 2003;
accepted after revision November 20, 2003.
Address correspondence to K. Khalili
(Korosh.Khalili{at}uhn.on.ca).
Introduction
Antiphospholipid-antibody syndrome manifests clinically as recurrent venous
or arterial thrombosis, thrombocytopenia, or recurrent fetal loss
[1]. It is associated with
elevated titers of IgG anticardiolipin antibody with or without lupus
anticoagulant. Adrenal infarction is a rare complication of
antiphospholipid-antibody syndrome and either is due to thrombosis of the main
adrenal vein or is secondary to microvascular thrombosis in the parenchyma. It
is most often accompanied by adrenal hemorrhage
[2] either subsequent to
ischemic necrosis or as a result of anticoagulant therapy. Previous reports of
adrenal infarction in patients with antiphospholipid-antibody syndrome have
been associated with or attributed to adrenal hemorrhage.
We describe a case of a 42-year-old man with a known diagnosis of
antiphospholipid-antibody syndrome, who, within 1 week, developed sequential
adrenal infarcts with no evidence of adrenal hemorrhage. After extensive
review of the literature, we believe this is the first case showing adrenal
infarction with no associated hemorrhage visualized on both CT and MRI. The
clinical relevance of showing adrenal hemorrhage relates to adjustments that
may be required in the anticoagulation therapy of patients with
antiphospholipid-antibody syndrome.
Case Report
A 42-year-old man presented to the emergency department in January 2002
with acute onset of left flank pain. He had been diagnosed with
antiphospholipid-antibody syndrome 12 years earlier after developing recurrent
deep vein thromboses and was initially treated with warfarin sodium (Coumadin,
Bristol-Myers Squibb Pharma). In December 2001, his treatment was changed
because of erratic international normalized ratio values. At the time of his
admission, he was being treated once daily with 18,000 U of
low-molecular-weight heparin dalteparin sodium (Fragmin, Pfizer) and 75 mg per
day of clopidogrel bisulfate (Plavix, Bristol-Myers Squibb Pharma).
Hematologic investigations showed hemoglobin levels of 144 g/L and a platelet
count of 130 x 109/L. His activated partial thromboplastin
time was greater than 150 sec, and his international normalized ratio was
1.35. His serology was positive for anticardiolipin antibodies and DNA
antinuclear antibodies.
The patient was given a provisional diagnosis of left-sided renal colic and
was initially scanned with unenhanced CT. The study was negative for renal
tract calculi but showed enlargement of the left adrenal gland with mild
inflammatory changes in the adjacent fat
(Fig. 1A). Given the patient's
history of antiphospholipid-antibody syndrome, the possibility of adrenal
infarction was raised, and an MRI of the adrenal glands was arranged to look
specifically for the presence of hemorrhage in the gland. The images confirmed
left adrenal infarction, with some edema in the periphery of the gland. No
high-signal areas were identified on the fast spoiled gradient-recalled echo
T1-weighted images to suggest hemorrhage
(Fig. 1B), and also no evidence
of parenchymal enhancement was found (Fig.
1C). At this stage, the right adrenal gland was normal. One day
after admission, his platelet count fell to 112 x 109/L, and
it was thought that he was developing heparin-induced thrombocytopenia because
the result of his immunoassay was positive. As a consequence, his
anticoagulation regime was changed to 2,500 U twice a day of danaparoid sodium
(Orgaran, Orgaran).
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Fig. 1A. —42-year-old man who presented with left flank pain and was
given provisional diagnosis of renal colic. Unenhanced CT scan shows enlarged
left adrenal gland (arrow), which is of normal attenuation. Note mild
inflammatory change in surrounding fat.
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Fig. 1B. —42-year-old man who presented with left flank pain and was
given provisional diagnosis of renal colic. Fast spoiled gradient-recalled
echo coronal out-of-phase T1-weighted MR image obtained 2 days after A
shows homogeneous intermediate signal intensity (arrow) throughout
enlarged left adrenal gland. Note normal contralateral adrenal gland.
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Fig. 1C. —42-year-old man who presented with left flank pain and was
given provisional diagnosis of renal colic. Coronal T1-weighted
gadolinium-enhanced MR image depicts capsular but no parenchymal enhancement
(arrow) in infarcted left adrenal gland.
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Four days after his admission, he developed new right-sided flank and back
pain. At this stage, his activated partial thromboplastin time was 128 sec. CT
confirmed mild, diffuse thickening of the right adrenal gland, similar to the
left-sided changes of his initial CT, highly suspicious for developing right
adrenal infarction. MRI of the adrenal glands performed 8 days after his
admission confirmed bilateral adrenal infarction with no evidence of
hemorrhage (Figs. 1 D and
1E).
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Fig. 1D. —42-year-old man who presented with left flank pain and was
given provisional diagnosis of renal colic. Repeated fast spoiled
gradient-recalled echo axial out-of-phase T1-weighted MR image, obtained 4
days after first presentation (A) due to contralateral pain, confirms
thickening of right adrenal gland (arrow), which is of homogeneous
intermediate signal, together with previously shown swollen left adrenal gland
(A and B). No evidence of hemorrhage is seen in either
gland.
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Fig. 1E. —42-year-old man who presented with left flank pain and was
given provisional diagnosis of renal colic. Axial T1-weighted
gadolinium-enhanced image shows lack of contrast enhancement in both adrenal
glands consistent with infarction. Note that degree of capsular enhancement in
left adrenal gland is now less than that on previous MR image (C) and
is less than that in right adrenal gland (arrow).
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The patient has subsequently developed adrenal insufficiency secondary to
the infarction. Results of his cosyntropin (Cortrosyn, Organan) stimulation
test showed a maximal cortisol level of 85 nmol/L (normal range, 170–660
nmol/L), and he is currently requiring cortisone replacement. A recent CT scan
obtained for other complications related to his underlying condition confirms
that now both adrenal glands are severely atrophic
(Fig. 1F).
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Fig. 1F. —42-year-old man who presented with left flank pain and was
given provisional diagnosis of renal colic. Follow-up CT scan obtained 4
months after first admission (A) shows that left adrenal gland
(arrow) is now atrophic, and only small nodule of tissue in right
adrenal gland (arrowhead) remains.
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Discussion
Our aim in presenting this case report is threefold: to highlight this
rare, but potentially lethal complication of antiphospholipid-antibody
syndrome; to present an illustrated example of progression of the disease
process; and to show that gross hemorrhage need not occur with the infarction.
The latter fact has therapeutic implications.
Adrenal infarction or hemorrhage should be considered as a potential cause
of back or abdominal pain in patients with an underlying hypercoagulable state
along with other conditions such as mesenteric infarction. In a recent review
article of patients with antiphospholipid-antibody syndrome who had adrenal
involvement, abdominal pain was described in 55% of patients at the time of
presentation and adrenal insufficiency was the first manifestation of
antiphospholipid-antibody syndrome in 31 of the 86 patients
[2]. Unlike the general
population, in which up to 80% of adrenal failure is secondary to autoimmune
adrenalitis, the pathogenesis of adrenal gland failure in patients with
antiphospholipid-antibody syndrome is most commonly hemorrhagic infarction
secondary to thrombosis in the adrenal vein
[3]. Adrenal hemorrhage can
also occur as a direct consequence of anticoagulant treatment for the
underlying condition [4].
There has been controversy in the literature for several decades as to the
underlying cause of adrenal infarction and hemorrhage and as to whether
hemorrhage results from infarction or precedes it. The most detailed ex vivo
study was published in 1976 [5]
and concluded that venous thrombosis was likely to be the antecedent to
hemorrhage in the gland and that this could occur at a microvascular level or
in the main adrenal vein. The gland has a rich arterial supply from branches
of the inferior phrenic artery, the aorta, and the renal artery, forming a
plexus around the outer zona glomerulosa. There is however a single draining
vein and therefore an abrupt change in flow dynamics in the medullary
sinusoids draining into the adrenal vein. This change may predispose the gland
to microvascular thrombosis in situations of procoagulable states and during
episodes of hypotension, leading to infarction. It is at the time of
reperfusion through these necrotic vessels that hemorrhage is thought to
occur, especially in situations of prolonged anticoagulation therapy
[6].
Heparin-induced thrombocytopenia is also a recognized cause of bilateral
adrenal swelling due to hemorrhage. The cause of the hemorrhage is again
thought to be secondary to microvascular thrombosis and subsequent ischemic
damage to the vascular endothelium
[6]. The lack of hemorrhage on
MRI performed in our patient indicates that although the patient was thought
to have heparin-induced thrombocytopenia, it is unlikely to have been the
cause for the sequential adrenal enlargement.
The abdominal pain has mainly been ascribed to hemorrhage within the gland,
but a recent article [7]
disputes this cause, suggesting that it is more likely to be due to ischemic
necrosis and associated inflammatory swelling. The findings in our patient
would support the latter view. In our extensive literature review, we found
five cases in which the adrenal glands on CT scans were swollen but of normal
density on an unenhanced study. This finding would suggest infarction with no
associated hemorrhage.
In one of these cases, it was postulated that there could have been
hemorrhage that was of normal density on CT
[8]; on the basis of the
experience with our patient, we believe this finding is unlikely. In none of
these other cases was MRI performed after CT. MRI provides a highly sensitive
method of detecting hemorrhage, and as we have shown, offers exquisite detail
of the adrenal glands. Gradient-echo T1-weighted images show hyperintense
areas corresponding to methemoglobin and hypointense regions in the more
chronic stage due to hemosiderin. T2-weighted images show edematous change
related to the inflammatory swelling of the adrenal gland. The fact that
relatively few cases of pure adrenal infarction have been reported is likely,
to some degree, to reflect the fact that MRI is not often performed in such
cases. The absence of blood products is not fully appreciated on CT.
The importance of showing the presence or absence of macroscopic adrenal
hemorrhage is related to future treatment of the underlying condition of these
patients. A risk of recurrent hemorrhage always exists if anticoagulation
therapy is restarted, although the risk of thrombosis in a patient with
untreated antiphospholipid-antibody syndrome has to be weighed against the
potential for recurrent adrenal hemorrhage. After macroscopic hemorrhage, the
anticoagulant regime may well be altered or stopped entirely, depending on the
clinical history. If pure infarction is shown, as with our patient,
anticoagulation therapy does not offer such a potential increased risk, and
the regime is unlikely to be changed.
We conclude that adrenal infarction is a rare complication of
antiphospholipid-antibody syndrome but should be considered in the
differential diagnosis for causes of acute abdominal pain in patients with
underlying hypercoagulable conditions. MRI may be used to assess underlying
hemorrhage in the adrenal glands if this is not apparent on the initial
CT.
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Introduction
Case Report
