British Journal of Radiology (2003) 76, 566-569
© 2003 British Institute of Radiology
doi: 10.1259/bjr/29409091
MRI diagnosis of bilateral adrenal vein thrombosis
M F Ryan, BSc, MB, FFR RCSI, FRCR1,
J P Murphy, FFR RCSI, FRCR, FRCPC2,
R Jay, MD, FRCPC3,
J Callum, MD, FRCPC3 and
D MacDonald, MD, FRCPC4
1 Department of Clinical Radiology, Mayo General Hospital, Castlebar, Co. Mayo, Ireland, Departments of 2 Medical Imaging, 3 Medicine and 4 Clinical Pathology, Sunnybrook and Women's College Health Sciences Centre and the University of Toronto, Toronto, Ontario, Canada
Correspondence: Max F Ryan
 |
Abstract
|
|---|
We report a case of bilateral adrenal vein thrombosis in an adult female who had a history of breast cancer. The patient does not have clinical, serological or imaging evidence of metastatic disease 14 months from the initial diagnosis. Adrenal vein thrombosis is a rare entity. There have been no previous reports specifically stating an association between adrenal vein thrombosis and hypercoaguability, but there are many cases in the literature documenting venous thrombosis elsewhere within the body in patients with hypercoaguable states. Laboratory testing performed to exclude a hypercoaguable state, revealed heterozygosity for the Factor V Leiden mutation/activated protein C resistance and elevated factor VIII levels [3660 IU l-1 (<1500)]. This is the first reported case of bilateral metachronous adrenal vein thrombosis in which MRI established the diagnosis.
|
Introduction
|
|---|
Bilateral primary adrenal haemorrhage owing to adrenal vein thrombosis is a rare cause of flank pain. Flank pain is a non-specific clinical symptom, nevertheless in a patient with a history of malignancy, metastatic disease should be considered in the differential diagnosis. We report a case of recurring adrenal vein thrombosis, by which the diagnosis was confirmed by MRI.
|
Case report
|
|---|
A 67-year-old woman presented with a 3-day history of acute severe right flank pain and fever. The patient 3 years earlier, had invasive ductal breast carcinoma treated by mastectomy, radiation and chemotherapy. There were no clinical signs of local tumour recurrence, or metastatic disease and the patient was not presently on chemotherapy.
On admission the patient had mild pancytopenia; haemoglobin 60 (120–160) g l-1, haematocrit 0.188 (0.370–0.490) L/l, mean corpuscular volume 111 (80–100) fl, red blood cell (RBC) count 1.69 (4–5.5 x 1012/l), white cell count (WCC) 1.2 (4–11 x 109/l), platelet count 141 (150–400 x 109/l), mean platelet volume 10.7 (5–15) fl. Bone marrow examination revealed trilineage dysplasia consistent with secondary myelodysplastic syndrome, presumed secondary to FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for breast cancer. Liver function tests were normal. The patient's anaemia was treated with blood transfusions.
Ultrasound (US) showed a 3.0 x 2.1 x 1.3 cm non-specific hypoechoic nodule in the right adrenal gland (Figure 1
). Non contrast-enhanced CT scan initially performed to exclude renal colic showed an ill-defined, heterogeneous, low attenuating (34 HU) nodule in the right adrenal gland associated with stranding of the periadrenal fat. A contrast enhanced scan performed at the same time demonstrated periadrenal connective stranding on the left side (Figure 2). These findings were reported as suggesting bilateral adrenal haemorrhage.
View larger version (122K):
[in this window]
[in a new window]
|
Figure 1. Sagittal ultrasound of the right upper quadrant, showing an enlarged heterogeneous hypoechoic right adrenal mass (arrow). The appearances were non-specific and the differential diagnosis included primary benign of malignant tumour, metastases and infection.
|
|
View larger version (131K):
[in this window]
[in a new window]
|
Figure 2. Contrast enhanced CT scan shows an ill defined, heterogeneous, low attenuating (30 HU) nodule representing haemorrhagic infarction in the media limb of the right adrenal gland (straight arrow) and stranding in the periadrenal fat. Increased stranding is evident in the periadrenal connective tissue fat of the left adrenal gland (curved arrow).
|
|
A pre- and post-contrast enhanced MR scan (with fat saturation) showed a mass within the body and medial limb of the right adrenal gland (Figure 3). This mass returned a signal isointense with the remainder of the gland on SPGR (spoiled gradient recalled acquisition in the steady state) T1 weighted and T2 weighted sequences consistent with deoxyhaemoglobin. The mass did not enhance following intravenous gadolinium contrast administration. The adrenal mass was continuous with a non-enhancing filling defect that followed the expected course of the right adrenal vein. The findings were consistent with thrombosis of the right adrenal vein and measured 3 mm in the intracaval portion (Figure 4).
View larger version (111K):
[in this window]
[in a new window]
|
Figure 3. Contrast enhanced axial SPGR (spoiled gradient recalled acquisition in the steady state) T1 weighted MR scan with fat saturation, shows a non-enhancing low signal intensity mass representing deoxyhaemoglobin in the right adrenal gland (arrow).
|
|
View larger version (104K):
[in this window]
[in a new window]
|
Figure 4. Contrast enhanced axial SPGR (spoiled gradient recalled acquisition in the steady state) T1 weighted MR scan with fat saturation, shows a filling defect that extends from the upper pole of the right adrenal gland into the inferior vena cava (curved arrow), following the expected course of the right adrenal vein. The lesion was of low signal intensity on both T1 weighted and T2 weighted sequences consistent with deoxyhaemoglobin.
|
|
Laboratory testing performed to exclude a hypercoaguable state, revealed heterozygosity for the Factor V Leiden mutation/activated protein C resistance and elevated factor VIII levels [3660 IU l-1 (<1500)]. Several other serological tests for a hypercoaguable state were performed. Plasma levels of Protein C, Protein S, antithrombin III and homocysteine were normal. Antiphospholipid and anticardiolipin antibodies were not detected and genotyping for Factor II variant and methyl tetrahydrofolate reductase revealed no mutations. Immunophenotyping with flow cytometry revealed normal expression of CD-55 and CD-59 excluding paroxysmal noctural haemoglobinuria as a cause for thrombosis. Serological tests for adrenal insufficiency (serum adrenocorticotrophin 4 (2–16) pmol l-1, cortisol 309 (190–690) mmol l-1) were negative. All other laboratory and imaging investigations including a CT scan of the chest, abdomen and pelvis, and an isotope bone scan were unremarkable, thereby virtually excluding metastatic disease. The patient was managed conservatively at this stage.
2 months later, the patient presented with a right lower limb deep venous thrombosis and was treated with low molecular weight heparin. 2 weeks later, while adequately anticoagulated (normal therapeutic Anti-Xa range of 0.5 to 1.0 u ml-1) the patient re-presented with left flank pain. CT scan showed diffuse enlargement of the left adrenal gland associated with periadrenal stranding (Figure 5). The right adrenal mass had resolved, but minimal periadrenal stranding persisted. Repeat MR scan showed complete resolution of the right adrenal mass and the adrenal vein thrombus. However, the left adrenal gland was now enlarged and associated with periadrenal stranding consistent with acute venous thrombosis (Figure 6).
View larger version (136K):
[in this window]
[in a new window]
|
Figure 5. Contrast enhanced CT scan shows diffuse enlargement of the left adrenal gland (arrow) and increased periadrenal connective tissue stranding of the adjacent fat. The right adrenal mass lesion had resolved, but minimal periadrenal stranding persists.
|
|
View larger version (140K):
[in this window]
[in a new window]
|
Figure 6. Axial SPGR (spoiled gradient recalled acquisition in the steady state) T1 weighted MR scan demonstrates periadrenal connective stranding evident on the left side (arrow). Complete resolution of the right adrenal mass and periadrenal connective tissue stranding was noted (not shown).
|
|
The patient remains free from evidence of metastatic carcinoma, 14 months from the initial diagnosis. The patient remains on anticoagulation therapy.
|
Discussion
|
|---|
Metachronous adrenal vein thrombosis has not been previously reported. The clinical presentation was attributable to secondary adrenal haemorrhage.
Persistently elevated Factor VIII levels (>1500 IU l-1) have been associated with a four- to eight-fold increased thrombotic risk over baseline. It is thought that the risk increases in a dose dependent fashion [1, 2]. This is a relatively newly observed thrombophilia and the clinical associations for this are still somewhat unclear. In the normal population approximately 10% of patients have elevated Factor VIII levels (>1500 IU l-1) and 5% are heterozygous for Factor V Leiden in Caucasian populations [3]. The combination of Factor V Leiden and elevated Factor VIII levels may constitute a significantly strong risk to account for this unusual presentation.
Interestingly, despite continuous and adequate anticoagulation therapy, contralateral adrenal vein thrombosis occurred. Screening tests for heparin induced thrombosis-thrombocytopenia syndrome (HITTS), in which thrombosis may occur in any vascular bed were negative [4].
Some authors consider that paradoxical central vein thrombosis a result of haemorrhage rather than the cause, whereas others conclude the opposite [4].
There are several predisposing factors in adrenal vein thrombosis that include stress and age-related capillary fragility [4]. Other causes include, metastatic disease, trauma, the Waterhouse-Fredrickson syndrome, inferior vena cava (IVC) or renal vein thrombosis, severe infections, chronic respiratory diseases, hypothermia, disseminated intravascular coagulation and hypercoagulable states [4, 5]. Iatrogenic causes include surgical procedures and following adrenal venography [6, 7].
The histological changes are of infarction that may be patchy, in which case there is variable central haemorrhage and ischaemic necrosis [6].
The mechanisms of adrenal vein thrombosis include damage to adrenal sinusoids by exotoxins, endotoxins or by stasis with anoxia. Injury to vessel wall endothelium results in deposition of fibrin and thrombosis [6]. In addition, the structure of thrombi within adrenal veins is abundant in platelets and fibrin, which would suggest that platelets also play an important role [6]. Localization of thrombus to the adrenal vein is thought to be due to its unique anatomical structure and physiological function, which under certain circumstances, such as turbulence or wall irregularity, may cause local stasis of blood flow and platelet thrombosis [6].
Documented complications of adrenal vein thrombosis include adrenal haemorrhage, infarction, adrenal insufficiency and potential risk of subsequent pulmonary emboli [8].
Adrenal veins cannot be identified on CT or US but haemorrhagic venous infarction of the adrenal glands occurring as a consequence of adrenal vein thrombosis can be visualized by these imaging modalities. On US an enlarged, hypoechoic mass that becomes cystic on follow-up examinations suggests the diagnosis [9]. CT may show the different stages of secondary haemorrhage [9, 10]. Early in its course, haemorrhage causes gland enlargement and attenuation values of 40–90 HU are typical. Streaky changes of the periadrenal tissues also occur. Eventually cystic resorption and calcification occurs [9].
The MRI features of adrenal vein thrombosis have not been previously reported. The MR features were diagnostic, showing an adrenal mass and a non-enhancing filling defect that extended into the IVC and later into the contralateral adrenal and renal vein. These findings in a patient with known malignant disease must always raise the possibility of metastases. However, the imaging findings did not support a diagnosis of malignancy, as the lesions were small, they did not enhance and decreased in size over time.
MRI is specific in the diagnosis of adrenal haemorrhagic infarction, a complication of adrenal vein thrombosis [10]. A heterogeneous mass with variable signal intensity on both T1 weighted and T2 weighted images depending on its stage of evolution is typical [11]. In acute haemorrhagic infarction (1–3 days), deoxyhaemoglobin may appear as low signal intensity on both T1 weighted and T2 weighted images. In the early subacute phase (>3 days), intracellular methaemoglobin may appear as high signal intensity on T1 weighted and low signal intensity on T2 weighted images. In the late subacute phase (>7 days) extracellular methaemoglobin should appear as high signal on both T1 weighted and T2 weighted images. Secondary signs such as increased signal intensity within the periadrenal fat on T2 weighted images, and absence of enhancement should suggest the diagnosis [10, 11]. Follow-up examinations demonstrate a decrease in size of the haemorrhagic infarct and signal intensity changes such as an increase centrally and decrease peripherally support the diagnosis [11].
In summary, adrenal vein thrombosis is a rare cause of flank pain. The diagnosis of a hypercoaguagulable state causing venous thrombosis is one of exclusion, in particular those patients with a known primary malignancy. The superior contrast resolution of MRI makes it useful in establishing the diagnosis.
Received for publication April 8, 2002.
Revision received September 23, 2002.
Accepted for publication November 20, 2002.
|
References
|
|---|
- Kraaijenhagen RA, in't Anker PS, Koopman MM, Reitsma PH, Prins MH, van den Ende A, et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost 2000;83:5–9.[Medline]
- Kyrle PA, Minar E, Hirschl M, Bialonczyk C, Stain M, Schneider B, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med 2000;343:457–62.[Abstract/Free Full Text]
- Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001;344:1222–31.[Free Full Text]
- Granry JC, Houet JF, Delhumeau A. Hematoma of the adrenal glands and heparin. Ann Fr Anesth Reanim 1989;8:650–5.[Medline]
- Arnason JA, Graziano FM. Adrenal insufficiency in the antiphospholipid antibody syndrome. Semin Arthritis Rheum 1995;25:109–16.[CrossRef][Medline]
- Fox B. Venous infarction of the adrenal glands. J Pathol 1976;119:65–89.[CrossRef][Medline]
- Davidson JK, Morley P, Hurley GD, Holford NG. Adrenal venography and ultrasound in the investigation of the adrenal gland: an analysis of 58 cases. Br J Radiol 1975;48:435–50.[Abstract]
- Kawashima A, Sandler CM, Ernst RD, Takahashi N, Roubidoux MA, Goldman SM, et al. Imaging of nontraumatic hemorrhage of the adrenal gland. Radiographics 1999;19:949–63.[Abstract/Free Full Text]
- Zirinsky K, Auh YH, Rubenstein WA, Morrison HS, Sherman SJ, Kazam E. Computed tomography appearance of adrenal vein thrombosis. J Comput Tomogr 1987;11:216–8.[CrossRef][Medline]
- Provenzale JM, Ortel TL, Nelson RC. Adrenal hemorrhage in patients with primary antiphospholipid syndrome: imaging findings. AJR Am J Roentgenol 1995;165:361–4.[Abstract/Free Full Text]
- Hoeffel C, Legmann P, Luton JP, Chapuis Y, Fayet-Bonnin P. Spontaneous unilateral adrenal hemorrhage: computerized tomography and magnetic resonance imaging findings in 8 cases. J Urol 1995;154:1647–51.[CrossRef][Medline]
Top
Abstract
Introduction
