Adrenal hemorrhage and hemorrhagic masses; diagnostic workup and imaging findings

Abstract

Adrenal hemorrhage (AH) is a rare condition. It can be traumatic or non-traumatic. Most common causes are septicemia, coagulopathy or bleeding diathesis, and underlying neoplasms. Other reported less common causes of AH are COVID-19 and neonatal stress. Clinical diagnosis of AH is challenging due to its non-specific presentation and occurrence in the setting of acute medical illness. Therefore, most cases are diagnosed incidentally on imaging. Having high clinical suspicion in the proper clinical setting for AH is crucial to avoid life-threatening adrenal insufficiency that occurs in 16–50% of patients with bilateral AH. We discuss the clinical situations that predispose to AH, review the imaging features on different imaging modalities, highlight a variety of clinical cases, imaging features that should be concerning for an underlying neoplasm, and outline the potential role of interventional radiology in management of AH.

Introduction

Adrenal hemorrhage (AH) is a rare condition, with a reported prevalence of 0.14 and 1.8% in post-mortem studies.^1,2 AH can be caused by a variety of etiologic factors, including trauma, bleeding disorders, infection, stress, and bleeding related to an adrenal tumor. While traumatic AH is often unilateral, most systemic conditions causing spontaneous AH tend to result in bilateral hemorrhaging.³

The clinical diagnosis of AH is challenging, as patients may be asymptomatic or have a nonspecific clinical presentation (e.g. abdominal pain, hypotension, confusion, fever, decreased hemoglobin level [by 1.5 g dl⁻¹ or more]).⁴ Acute adrenal insufficiency is a life-threatening complication⁵ caused by massive bilateral adrenal hemorrhage that destroys more than 90% of the adrenal cortex.⁶ Manifestations of adrenal crisis are non-specific and can be misdiagnosed in patients with coexisting diseases or masked by ongoing supportive treatment.⁷ Therefore, historically the diagnosis of AH is most often made in post-mortem studies. However, with the increasing use of CT and MRI, many cases of AH are diagnosed incidentally during evaluation for other reasons.⁸ Early diagnosis of AH may alter the clinical outcome and allow timely intervention to prevent a rare but possible life-threatening decompensation.⁹ Our objective was to review the pathophysiology, etiology, imaging features on different modalities, and management of AH.

Pathophysiology

The unique blood supply of adrenal glands may be an important predisposing factor for the development of AH. Each adrenal gland has three arterial feeding vessels and a single draining vein.¹⁰ The sharp transition from the arteries to the capillaries around the zona reticularis of the gland is known as a “vascular dam” network.¹¹ This increases the susceptibility of the adrenal gland to hemorrhage and increases intraglandular blood pressure, particularly if the vein becomes thrombosed.¹¹ Stress and subsequent dramatic rise in catecholamines increase the vascularity and jeopardizes this vulnerable network.¹² Moreover, epinephrine is present in high concentrations at the adrenal vein, which leads to platelet aggregation and vasoconstriction.¹² Therefore, conditions of stress and coagulopathy can easily lead to AH.

Diagnostic work-up and utility of various imaging modalities

Plain radiography

Abdominal radiography is not indicated in the evaluation of AH. This modality rarely shows any abnormality in non-traumatic cases, unless egg shell or curvilinear calcifications, which imply chronicity, are present.⁷ In traumatic AH, radiographs may demonstrate pelvic, spine, or rib fractures.¹³

Ultrasonography

Ultrasonography is the imaging modality of choice in pediatric population because of their small body size, reduced volume of retroperitoneal fat, and relatively large adrenal glands,^14,15 in addition to avoiding early exposure to ionizing radiation. In neonates, normal adrenal glands appear as a hypoechoic cortex and echogenic medulla.

In the early stages of AH in neonates, the glands enlarge, develop irregular margins and a triangular appearance, and become hyperechoic.¹⁵ Typically, the bleeding is limited to the capsule, but if it ruptures, hemorrhage is seen in the retroperitoneal space and may extend inferiorly to scrotal sac resulting in scrotal hematoma.¹⁶ Color Doppler reveals an avascular structure. Over time, liquefaction occurs and a central hypoechoic area is formed that gradually increases in size. Follow-up ultrasonography will show shrinkage of the hematoma (Figure 1). Calcification may appear as early as 1 or 2 weeks after event onset.¹⁵ Resolution is expected within 3–9 months.¹⁷

Figure 1.

Longitudinal (A) grayscale ultrasound image of a 1-month-old newborn baby (36 week premature infant who was born via C-section). The baby was diagnosed with an adrenal cyst in utero. The images show a heterogeneous mass that measures up to 2.7 cm (arrow in a). The mass shows significant decrease in size in multiple follow-ups with near complete resolution after 1 year (arrow in b).

Although sonographic differentiation between AH and suprarenal masses in neonates may be difficult, serial ultrasonography and color Doppler can be helpful in making the correct diagnosis.¹⁵ Serial ultrasonography can show a decrease in size, change in echogenicity, and resolution of AH with development of calcification in longstanding cases. Additionally, color Doppler demonstrates no vascularity in AH compared to increased vascularity in neuroblastoma.¹⁵ A high level of urinary catecholamine is also an indicator of neuroblastoma.¹⁸

The kidneys should be carefully evaluated to exclude potential possibility of underlying renal vein thrombosis (RVT), which is commonly associated with the setting of AH in neonates.¹⁹ In such setting, the hemoconcentration and hypoperfusion lead to interlobular venous thrombosis in the renal cortex that extends into larger veins. The kidney would be swollen, with increased echogenicity of the renal parenchyma and interlobular vessels.¹⁵ Although the association of AH and RVT is not common in adults, detection of an adrenal mass in the setting of RVT should raise the suspicion of adrenal hemorrhage.²⁰ Medullary adrenal vein thrombosis secondary to RVT may be a more important etiological factor in this adult population.²⁰

Computed tomography

CT is the imaging modality of choice for evaluating adrenal crises in severely ill patients.²¹ CT protocols can vary and usually depend on the patient’s clinical presentation. In acutely ill patients, an unenhanced CT is usually sufficient without need for a dedicated adrenal washout protocol. This technique is often reserved for differentiating metastasis from lipid-poor adenoma.²² In acute hemorrhage, the gland enlarges to a rounded or ovoid shape, with high or mixed attenuation. The attenuation value of AH is greater than that of simple fluid (50–70 HU).¹⁰ Usually, no appreciable contrast enhancement is noted (Figure 2). In its mildest form, AH results in a train track appearance of the gland, with central hypoattenuation and preserved peripheral enhancement.¹ Periadrenal infiltration and retroperitoneal bleeding may be seen.

Figure 2.

Axial CT image without i.v. contrast (a) and multiple post-contrast axial CT images (b, c) showing a heterogeneous left adrenal mass with high attenuation areas within in the pre contrast image (arrow), with adjacent left retroperitoneal enhancement. The lesion shows no significant enhancement in post-contrast images (b, c). The mass was surgically resected and was pathologically proven to represent adrenal adenoma with hemorrhage.

In chronic AH, the volume of hemorrhage shrinks over time, and its CT attenuation decreases to the level of fluid attenuation in chronic cases. On follow-up imaging, complete resolution and absence of enhancement exclude the possibility of underlying neoplasms.¹⁰ Later, the adrenal hemorrhage may appear as an atrophied isoattenuating gland or non-enhancing pseudocyst, which often calcifies after 1 year (Figure 3).¹ Follow-up imaging is recommended to ensure resolution and exclude underlying neoplastic masses.

Figure 3.

A mass is present within the left adrenal gland (a) with peripheral curvilinear wall calcifications. This demonstrates fluid attenuation, with wall calcification; features of typical pseudocyst. CT and MR images in a different patient: Axial contrast enhanced CT (b) demonstrates a large heterogeneous predominately hypoattenuating mass with a focus of peripheral calcification (curved arrow). Axial T₁ weighted (c) and coronal T₂ weighted (d) MR images demonstrate high signal intensity on T₁WI and heterogeneous mixed signal intensity on T₂WIs, consistent with internal hemorrhage. Based on the large size and heterogeneous appearance of this mass, this was prospectively diagnosed as adrenocortical carcinoma. This mass was surgically resected and was pathologically proven to represent hemorrhagic pseudocyst.

Dual-energy CT (DECT) can be used to accurately diagnose acute AH from a single post-contrast acquisition with no need for true non-contrast phase, delayed phase, or further imaging work-up. Virtual non-contrast imaging in DECT demonstrates hyperdensity with no active uptake in the iodine overly imaging confirming AH. DECT has a higher contrast resolution than conventional CT that enables dose reduction of injected contrast material. Moreover, it precludes phases from CT protocol performed for gastrointestinal bleeding cases leading to dose reduction by up to 30%. Finally, several studies show that DECT images are more accurate than conventional CT images in acute gastrointestinal bleeding.²³

Magnetic resonance imaging

Although MRI is more sensitive than CT in diagnosing AH,²⁴ it is not routinely used. MRI can identify low-level enhancement of underlying neoplastic masses, which may be masked on CT owing to the presence of acute bleeding. MRI can also be performed to avoid ionizing radiation, as in the case of pregnancy and neoplasms of childhood. The MRI protocol includes a coronal localizer using single-shot spin echo to offer an anatomic overview of the abdomen. T₂ weighted gradient echo (in-phase and out-of-phase) sequences are used, with the longer duration assigned to the in-phase echo for detection of intravoxel fat in adrenal nodules. Fat-suppressed T₂ weighted images are used to detect hyperintensity of pseudocysts, cysts, and the light bulb sign of some pheochromocytomas. Subtraction MR imaging can be vital for the assessment of post-contrast enhancement of atypical adrenal lesions, and it can be used in the evaluation of underlying neoplasms.²⁵ The subtraction technique will remove any signal from simple blood products, as they do not contain an enhancing element, and will highlight the presence of an underlying mass. Contrast-enhanced imaging is also useful in lesions suspicious for adrenocortical carcinomas to determine the presence of vascular invasion.²⁶

MRI can precisely determine the age of blood products; if imaging is performed less than 7 days after onset (acute phase), blood will be hyperintense on T₁ weighted and hypointense on T₂ weighted images. Between 7 days and 7 weeks (subacute phase), the hypointense signal on T₂ weighted images gradually changes to a hyperintense signal. After 7 weeks (chronic hematoma), both T₁- and T₂ weighted images show a hypointense signal for blood products.^10,27 In chronic AH, the glands appear as cystic lesions with heterogenous signal intensity. Moreover, due to hemosiderin deposition, gradient echo imaging can be helpful in showing the blooming effect. Calcifications are not well appreciated on MRI, but loss of signal intensity may be seen at the periphery of the lesion (Figure 4).^1,27

Figure 4.

Multiple CT (a) and MR (b, c) images in a 39-year-old female with incidentally discovered left adrenal lesion. The lesion has wall calcifications (arrow in a), without post-contrast enhancement, this calcification appears hypointense on T₂ weighted image (arrow in c). Imaging features are consistent with an adrenal cyst with calcifications, possible related to old hemorrhage.

Positron emission tomography/CT

PET/CT is not indicated in AH but may be helpful in diagnosing an underlying neoplastic lesion. Fludeoxyglucose (FDG) uptake in adrenal lesions can be useful for differentiating benign from malignant lesions. A meta-analysis that included patients with incidentally discovered adrenal lesions and those with known cancers showed that FDG PET/CT had 97% sensitivity and 91% specificity for differentiating malignant from benign adrenal lesions.²⁸

Normal adrenal glands show relatively low FDG uptake that is similar to or slightly lower than background activity in the liver, whereas an adrenal lesion-to-liver ratio of more than one indicates malignancy.²⁹ PET/CT imaging findings that favor underlying tumor include a metabolic active lesion with increased FDG uptake (Figure 5) and intralesional calcification in the setting of acute AH. An underlying hemorrhagic tumor must always be considered in the differential diagnosis, particularly in the presence of known malignancy and in the absence of other AH risk factors.³⁰ False-positive PET/CT results have been reported for adenomas, myelolipomas, and adrenal hyperplasia; on the other hand, false-negative results have been described for small lesions, those with large necrotic components, and metastasis from neuroendocrine tumors and bronchoalveolar carcinomas, as those malignancies are known for their low FDG activity.²⁹

Figure 5.

53-year-old man with intermittent abdominal pain radiating to the back. Axial T₁ FS image (a) shows large bilateral adrenal hemorrhagic masses. PET/CT images (b) demonstrate necrotic bilateral adrenal masses with FDG avid peripheral foci (straight arrow). Additionally, there is a large RP FDG avid mass (curved arrow). Other images show large bilateral adrenal hemorrhagic masses without significant enhancement. Surgical pathology consistent with bilateral adrenal hemorrhagic metastases, likely from a retroperitoneal high-grade leiomyosarcoma. FDG, fludeoxyglucose; PET, positron emmision tomography; RP, retroperitoneal.

Etiology

Trauma

Traumatic adrenal gland injury was first described in 1863.³¹ It occurs in less than 5% of blunt force abdominal injury cases.^32,33 Trauma is the most common cause of unilateral AH³⁴ and mostly occurs on the right side.¹³ This right-sided predisposition may be secondary to the risk of the right adrenal gland being crushed between the liver and spine leading to deceleration forces that can shear the adrenal arterioles, and to the inferior vena cava compression that raises intra-adrenal venous pressure acutely in the right adrenal gland.³⁵

Isolated traumatic injury to the adrenal gland without any other injuries has been reported.^36,37 However, injuries to the liver and right kidney often accompany right adrenal gland injury, and left adrenal injuries are frequently associated with splenic or pancreatic trauma.¹³ Although most traumatic AH cases involve severe abdominal pain,^36,37 occasionally they may be associated with only mild abdominal pain.³⁵ Adrenal injury frequently indicates increased of trauma severity; patients with adrenal injury have a mortality rate 2- to 5-times higher than that of those who experience trauma without an adrenal injury.^34,38 A recent study has been published showed no increase in mortality among patients with blunt abdominal injury however, around 98% of patients in the studied database experienced just adrenal contusion or cortical laceration.

Ultrasonography is insufficiently for evaluating AH in adult population.¹³ CT with contrast is therefore the investigation of choice. In the acute setting of abdominal trauma, the portal venous phase is best to detect parenchymal organ injury.³⁹ Non-contrast CT can be used in patients with acute kidney injury. Moreover, multiplanar sagittal and coronal reconstruction help in image post-processing.

The main CT findings indicative of AH after abdominal trauma are adrenal enlargement, with a reported mean diameter of 2.8 cm, periadrenal fat stranding of up to 89%, and adjacent organ injuries.^33,40 On non-enhanced CT, acute bleeding shows high attenuation relative to muscles (50–90 HU). Although hematoma usually presents on the initial imaging scan, adrenal enlargement that progresses to adrenal hematoma on the following day has been identified.³⁴ Traumatic AH was noted in 1% of children who presented to a trauma unit over a decade; in most of those cases, thickening of one limb of the adrenal gland was visualized.⁴¹

The American Association of Trauma and Surgery has published the following grading system for adrenal gland injury: Grade 1: contusion and adrenal enlargement; Grade 2: injury limited to the cortex area (<2 cm); Grade 3: injury extended to the medulla (>2 cm); Grade 4: injury involving more than 50% of the gland; and Grade 5: injury involving all of the gland or occurrence of avascular avulsion.

Due to the possibility of bleeding into a preexisting adrenal neoplasm,⁸ CT follow-up may be recommended to rule out an enhancing mass.³⁵ Resolution of the hemorrhage occurs with time. Therefore, most cases of traumatic AH are treated conservatively.³⁵

MRI is not routinely used in the acute setting of trauma, but it is used in non-emergent cases to evaluate the age of a hematoma and the presence of an underlying lesion.

Heparin-induced thrombocytopenia after anticoagulants

AH is a rare complication of anticoagulant therapy.⁴² Heparin-induced thrombocytopenia (HIT) can be identified as the cause of AH when HIT antibodies are present; however, AH can also be associated with a negative HIT antibody test.⁴³ High clinical suspicion is required for those who have non-specific symptoms such as abdominal distress, fatigue, or fever on day 4–12 after starting anticoagulant therapy.^43,44 To avoid the occurrence of adrenal insufficiency, these symptoms should not be ignored.⁴⁴ The single draining adrenal vein makes the gland susceptible to outflow obstruction, which may facilitate thrombosis, raising the intra adrenal venous pressure and causing a subsequent AH.⁴⁴

Pregnancy

Studies report that AH is seen in 0.14–1.1% of pregnancies.⁴⁵ Although AH is rare during pregnancy, a high index of clinical suspicion is needed because AH can be life threatening for both mother and fetus.⁴⁶ The most common clinical symptoms are fever (42%) and abdominal pain (43%). Most of the cases present in the last trimester and appear as unilateral AH on imaging evaluation.⁴⁷ AH during pregnancy is believed to occur because adrenal hyperplasia in pregnancy increases the arterial blood supply to the gland, which combined with limited venous drainage and the hypercoagulable state during pregnancy leads to venous congestion and subsequent hemorrhage.⁴⁸ Drop of hemoglobin level is the most common laboratory abnormality. In one study, 69% of patients had a drop in their total hemoglobin level of over 1.5 g dl⁻¹.⁴⁹ The platelet count and coagulation profile are usually within normal limits.⁴⁶

Although ultrasonography is the initial imaging study in pregnancy, as its safety is well established, other imaging modalities is also required to confirm the diagnosis and to identify potential underlying neoplasms.⁴⁶ MRI is the most appropriate imaging modality for AH during pregnancy. The main advantages of MRI over other modalities are that it has the highest sensitivity and specificity among these imaging modalities, does not require ionizing radiation, and is not operator-dependent.⁴⁹ The American College of Radiology affirms the appropriateness of non-contrast MRI in the setting of acute abdominopelvic pain in pregnancy when a non-gynecological cause is suspected.⁵⁰ Gadolinium contrast use is not recommended at any stage of pregnancy unless the potential benefits clearly justify the possible risks.^51,52 The MRI protocol for adrenal gland imaging includes heavy T₂ weighting, T2 with fat suppression, and T1 gradient echo acquisition in-phase and out-of-phase. Since the treatment of AH during pregnancy is usually conservative, a follow-up MRI or CT is recommended to confirm the resolution of hematoma.⁴⁶ Preterm delivery may be indicated if AH is associated with eclampsia or pre-eclampsia or if the patient’s condition is unstable or worsening.⁵³ Close monitoring of the fetus is warranted, and vaginal delivery can be undertaken safely if the patient’s condition is stable.⁴⁶

Systemic lupus erythematosus and antiphospholipid syndrome

Systemic lupus erythematosus and antiphospholipid syndrome have been associated with AH due to venous thrombosis.^6,54 A study that followed up on the outcomes of patients with bilateral AH for an average of 3.5 years (range, 0.3–28.1 years) suggested a relatively good prognosis for patients with antiphospholipid syndrome who survived the acute stage of AH (Figure 6).⁵⁵ The rate of recurrent thrombosis in that study was estimated to be around 2.9% per patient/year.⁵⁵ Since recurrence of thrombosis in patient with antiphospholipid syndrome is a major predictor of morbidity and mortality, the recommendation is to set the international normalized ratio above 3.⁵⁶

Figure 6.

57-year-old male with non-traumatic bilateral adrenal hemorrhagic lesions. The patient has anti-phospholipid syndrome with anticoagulation. Axial CT image without contrast shows near symmetric enlargement of the bilateral adrenal glands with high attenuation lesions without significant enhancement (a). The lesions have homogenous low T2 signal (c), and heterogenous intermediate bright T1 signal with high signal of the periphery (d).

Initial Imaging can help predict the likelihood of functional recovery. If imaging shows areas of normal morphology within their adrenal glands, patients are likely to experience a partial functional recovery of their adrenocortical activity.⁵⁵ On the other hand, severely atrophic glands may lead to irreversible adrenal failure.⁵⁵

COVID-19 disease

The pandemic caused by COVID-19 is an emerging challenge. Several studies show the association between coagulopathy and COVID-19.⁵⁷ Reports have shown that patients infected with COVID-19 are at risk of coagulation activation, resultant thrombosis and disseminated intravascular coagulation after consumption of coagulation factors.⁵⁸ This coagulation disorder may cause thrombosis of the adrenal vein that leads to AH.⁵⁹ A few case reports have shown bilateral AH and signs of adrenal insufficiency in patients who presented with COVID-19.^59,60 Four cases of antiphospholipid syndrome have been described in which the patients developed bilateral AH after presenting with COVID-19.⁶¹ All of these patients were between 60 and 70 years old; three were in critical condition with a history of cerebral infarctions, while the fourth was in stable condition and developed primary adrenal insufficiency.⁶¹

The symptoms of AH are similar to those of COVID-19 (nausea, fatigue, malaise, and fever), so they could go unnoticed in patients with COVID-19 and require a high degree of clinical suspicion. A complete autopsy study of patients who died with severe COVID-19 showed that around 42% of patients, mostly males, had adrenal lesions. Most of the adrenal lesions detected in the autopsies were identified as cortical lipid degeneration, necrosis, focal inflammation, or hemorrhage.⁶² Damage to the adrenals due to COVID-19 may compromise the body’s ability to control the inflammatory response. This may explain the efficacy of corticosteroids against COVID-19, as shown in recent trials.⁶³ In published case reports, patients showed improvement with supportive treatment and glucocorticoid replacement.^60,64

Sepsis

Waterhouse-Friderichsen syndrome was originally described in 1911 as massive adrenal hemorrhage related to sepsis (Figure 7).⁶⁵ The bacterial endotoxins release pro-inflammatory cytokines that can induce intravascular changes in the adrenal vein and result in parenchymal adrenal hemorrhage.⁶⁶ Neisseria meningitidis is the most common bacterial pathogen associated with Waterhouse-Friderichsen syndrome. Other bacterial pathogens that have been reported include Pseudomonas aeruginosa, Neisseria gonorrhoeae, Haemophilus influenzae, and Escherichia coli.⁶⁷ Viral infections such as cytomegalovirus, Epstein Barr virus, and parvovirus B19 have also been reported to cause bilateral AH. Heitz and colleagues described a rare case of bilateral AH as a complication of primary varicella zoster infection in an adult.⁶⁸

Figure 7.

67-year-old male patient with 2 weeks of pneumonia. There are bilateral adrenal masses (Straight arrows in a). Enhanced Axial CT performed after 2 weeks (b) demonstrated resolution of the previously noted adrenal masses (curved arrows) indicative sepsis-related bilateral adrenal hemorrhages (Waterhouse-Friedrickson syndrome).

The prognosis of Waterhouse-Friderichsen syndrome depends on the timeliness of the diagnosis and severity of the disease. The mortality rate is around 15% in patients with acute bilateral adrenal bleeding and rises to 50% when the diagnosis is delayed.⁶⁹ Of the patients who have recovered, some have needed continuous replacement of their mineralocorticoid and glucocorticoid hormones, whereas a few patients have not needed permanent hormone replacement.⁷⁰

Neonatal stress

AH is more common in neonates than in adults. One possible explanation is that the adrenal glands are relatively larger and more vascularized in neonates than in adults.⁷¹ Risk factors for AH in infants include diabetic mother, difficult labor, asphyxia, and fetal acidemia.¹⁵

AH is more common in males, possibly because of their higher birth weight.¹⁵ Almost 70% of neonatal AH cases occur on the right side, as this side is more affected by changes in venous pressure, while only 10% of neonatal AH cases are bilateral.⁷²

Clinical manifestations are variable and in some cases are totally absent.¹⁵ Unexplained jaundice is the most common presentation and has been reported in 75% of cases according to a prior retrospective study.⁷¹ In cases of patent processus virginals, retroperitoneal hemorrhage may present as a scrotal hematoma.⁷³ This hematoma is reported in the absence of history of trauma.¹⁶

Ultrasonography is the investigation of choice in cases of neonatal AH.⁷⁴ The differential diagnosis includes neuroblastoma and suprarenal masses.

Neonatal adrenal hemorrhage is usually self-limited and typically resolves within 90 days.^15,71

Neoplastic masses

Both benign and malignant neoplasms involving the adrenal gland can lead to AH. In patients without a known risk factor for AH, it is necessary to exclude an underlying neoplastic process.²⁵ Evaluation for areas of enhancement on imaging is critical as this raises the suspicion for an underlying mass.

Pheochromocytoma

Pheochromocytoma is the most common cause of AH due to underlying primary adrenal tumor.²⁵ AH within pheochromocytoma has been recognized as a rare but highly lethal event. Around 50 cases have been reported in the literature, including one case with massive bleeding.⁷⁵ Pheochromocytoma commonly presents with hypertension, episodic palpitation, and perspiration.⁷⁶ These tumors have low attenuation on CT (36 ± 10 HU). On unenhanced CT image, the sensitivity of excluding pheochromocytoma is around 99% for lesions with attenuation value below 10 HU.⁷⁷ Pheochromocytomas enhance during the portal venous phase more than during the arterial phase. On MRI, pheochromocytomas typically demonstrate marked hyperintensity on T₂ weighted MR images (light bulb sign); however, a third of the cases do not demonstrate increased signal intensity. Moreover, on out-of-phase MRI, no signal loss is noted because pheochromocytoma does not contain a large portion of intracellular fat.⁷⁸ After gadolinium administration, pheochromocytoma shows a prolonged heterogeneous enhancement. Histologically, a malignant pattern is present in 10% of cases²⁵ (Figure 8).

Figure 8.

Multiple MR images before and after contrast. There is a 6.5 cm heterogeneously T2 hyperintense (a, straight arrow) right adrenal mass with multiple foci of T1 hyperintensity (b) compatible with intralesional hemorrhage. Peripheral enhancement of the right adrenal mass in post contrast images. Filling defect within the IVC (c, arrow head) adjacent to the right adrenal mass consistent with thrombus, possibly tumor thrombus. Patient underwent right adrenalectomy with en bloc IVC wall resection and reconstruction. The adrenal mass proved to be pheochromocytoma and the IVC filling defect turned out to be an organized bland thrombus. IVC, inferior vena cava.

Adrenocortical carcinoma

Adrenocortical carcinoma is an uncommon cause of AH, representing around 1.8% of all cases.⁷⁹ Adrenocortical carcinomas are aggressive masses that are usually larger than 6 cm. They show heterogeneous enhancement on CT with relative contrast retention on delayed phases of enhanced CT (<40% washout). Adrenocortical carcinomas have central areas of hemorrhage and necrosis that lead to variable signal intensity on CT and MRI.²⁵ Therefore, suspicion for AH due to adrenocortical carcinoma should be elevated if a patient presents with a large adrenal lesion with areas of enhancement, especially if there is invasion of the venous system or adrenocortical hyperfunction.

Among tumors that radiologically simulate adrenal cortical carcinomas is papillary endothelial hyperplasia; which is a benign vascular proliferation that is accompanied by endovascular thrombosis. It shares CT characteristics of adrenal carcinoma mandating surgical resection and pathological evaluation⁸⁰ (Figure 9). Similarly, angiosarcoma is a rare malignant tumor that arises from the vascular endothelium with radiographic features resembling that of adrenal carcinoma (Figure 10). Diagnosing of primary adrenal angiosarcoma is challenging for pathologists, however obtaining a wide immunohistochemicial studies can help to reach the definitive diagnosis.⁸¹

Figure 9.

Axial CT image post-i.v. contrast administration showing a heterogeneous left adrenal mass with attenuation value of 35 HU. The mass showed progressively enhancing peripheral nodularity (white arrow). Surgical pathology showed a hematoma with secondary papillary endothelial hyperplasia. HU, Hounsfield unit.

Figure 10.

59-year-old patient presenting with acute left flank pain. Axial unenhanced and post-contrast CT images (a, b) demonstrate a large heterogeneous predominately hypoattenuating mass involving the left adrenal gland. This mass demonstrates hyperdense foci of presumably hemorrhage and/or calcification (a, arrows). There is a layering fluid in the left retroperitoneum (b, arrow). This appearance was interpreted by the radiologist to represent an adrenal hemorrhage. 6 months follow-up CT (c) demonstrates interval enlargement of the mass which mandated surgical resection. On surgery, this was found to represent adrenal angiosarcoma with intratumoral hemorrhage.

Metastases

The most common adrenal hemorrhagic neoplasms are metastases,⁷⁹ which represent around 20% of these tumors.⁸ These metastases are frequently secondary to bronchogenic carcinoma (Figure 11), renal carcinoma, breast carcinoma, and melanoma.²⁵ Bilateral metastases are most common, but unilateral metastasis has also been noted. On CT, adrenal metastases show higher density (>10 HU) of unenhanced attenuation and prolonged enhancement during the venous phase.⁸² Moreover, they are characterized by extensive necrosis and delayed contrast washout, which distinguishes metastasis from adrenal adenoma.⁸³ On MRI, metastases are hypointense on T₁ weighted and hyperintense on T₂ weighted images, although melanoma metastases may demonstrate hyperintense signal on T₁ weighted images.⁸² The ability to differentiate between adenoma and adrenal metastasis is an important feature of MRI. This differentiation can be appreciated through the lack of a signal drop on out-of-phase MR images. Functional imaging, such as positron emission tomography (PET), is helpful in distinguishing benign adrenal masses from distant metastasis.⁸⁴ It can also act as a second-stage imaging modality for the assessment of indeterminate adrenal lesions.⁸²

Figure 11.

61-year-old male with history of lung cancer presenting with abdominal pain and dropped hemoglobin level. Color Doppler ultrasound image (a) shows a large heterogeneous metastatic mass in the right adrenal fossa without significant Doppler flow. Axial (b) and coronal (c) post-contrast CT images show a 10.5 cm heterogeneous right adrenal mass (curved arrow) causing inferolateral displacement of the right kidney. Additionally, there is right retroperitoneal hemorrhage extending medially inferior to the right kidney.

Myelolipoma

Myelolipoma is a benign neoplasm that is incidentally discovered in less than 1% of the population.⁸⁵ Prior studies have reported the occurrence of a large myelolipoma associated with retroperitoneal hemorrhage.^85,86 The presence of macroscopic fat within the adrenal hemorrhage is diagnostic of bleeding myelolipoma (Figure 12). Myelolipomas typically appear hyperechoic on ultrasonography because of the presence of macroscopic fat.⁷² On CT, lesions show negative attenuation characteristic of macroscopic fat (−30 HU) combined with higher attenuation in areas with myeloid cells.⁷³.⁶⁹ As stated earlier in this article bleeding complicating myelolipoma has characteristic imaging appearance of various stages of blood degradation products. Conservative managment is recommended for small myelolipomas, while lesions larger than 4 cm or those that increase in size should be treated with surgical intervention to avoid complications.⁸⁵ Interventional radiology has a role in the treatment of retroperitoneal hemorrhage due to adrenal myelolipoma (Figure 12). Intraarterial embolization has been performed to control bleeding before elective excision of the myelolipoma is carried out.⁸⁷ Table 1 summarizes the neoplastic and non-neoplastic causes of AH with the important features of each cause.

Figure 12.

Large right retroperitoneal, predominantly fat-containing mass (a, straight arrow) in the right suprarenal fossa measuring up to 13 cm. The mass demonstrates high attenuation foci of active internal hemorrhage within (curved arrow). There is associated moderate retroperitoneal and perinephric hematoma. Selective catheterization of the vessels in the mass (c) showing a small aneurysm in the superior aspect of the mass (white circle). This vessel was super selectively catheterized and coil embolization was performed with no flow in the post embolization images (d, arrow). Images to another 51-year-old male with right bleeding adrenal myelolipoma (e). Axial CT image without contrast demonstrates a large heterogeneous lesion with fat (straight arrow) and high attenuation contents (curved arrow) content denoting intralesional hemorrhage. No significant post-contrast enhancement noted (f).

Table 1.

Causes of adrenal hemorrhage.

Neoplastic causes
Pheochromocytoma	Commonly is associated with hypertension and palpitation, mostly around (36±10 HU) on CT, and hyperintense on T2WI.
Adrenocortical carcinoma	Uncommon, usually masses are larger than 6 cm with heterogeneous enhancement
Papillary endothelial hyperplasia and adrenal angiosarcoma	Very rare, resemble adrenocortical carcinoma, and require pathological evaluation.
Metastasis	Extensive necrosis with delayed washout, lack of signal drop on out-of-phase MR images.
Myelolipoma	Presence of macroscopic fat.
Non-neoplastic causes
Trauma	Unilateral, mostly on the right side, usually other organs are injured.
Heparin-induced thrombocytopenia	Rare, usually 4–12 days after starting anticoagulation.
In pregnancy	Rare, usually unilateral in the last trimester, drop of hemoglobin is common.
Systemic lupus erythematosus and antiphospholipid syndrome	Accompanied with a history of recurrent venous thrombosis.
COVID-19	Usually old age, critical condition after COVID-19 infection, more in males.
Sepsis	Neisseria meningitidis is the most common pathogen.
Neonatal stress	Diabetic mother, difficult labor, asphyxia, and fetal academia. Often occurs unilaterally on the right side.

Management of adrenal hemorrhage

Clinical evaluation

A thorough clinical history and physical examination are important to rule out the presence of a primary tumor or metastasis to the adrenal gland. Hematocrit levels and blood pressure should be closely followed to detect persistent bleeding. Patient medications (e.g. anticoagulants) should be evaluated and their continuation or discontinuation discussed with the integrated care teams.⁸ Moreover, serum catecholamines should be measured to rule out functioning tumors like pheochromocytoma. This would help to avoid hypertensive crisis resulting from surgical intervention in an occult active tumor.⁸⁸ Although normally stressed patients may show high catecholamine levels, we can measure adrenocorticotrophic hormones (ACTH) to distinguish physiologically stressed patients (high ACTH) from those with an underlying adrenal tumor (low ACTH level).⁸⁹ Adrenal insufficiency should be evaluated in case of bilateral adrenal hemorrhage to avoid adrenal crisis.⁹⁰

Conservative vs surgical treatment

Conservative therapy should be considered in cases of bilateral AH and in patients with known risk factors for surgery such as septicemia and anticoagulant therapy. Interval imaging is recommended in patients who have no biochemical evidence of a functional tumor. Resolution of hematoma on serial imaging confirms the absence of neoplastic factors and can prevent surgical treatment.⁸

Endovascular embolization may be lifesaving in cases of AH that are refractory to red blood cell transfusion.⁹¹ Additionally, it is the preferred initial therapy for ruptured pheochromocytoma, as the emergent surgery has a 45% rate of mortality.⁸ Patients with unstable hemodynamic conditions, suspicion of bleeding from a neoplastic lesion, or massive retroperitoneal hemorrhage that does not respond to transfusion are candidates for transarterial intervention.⁹² which may offer better outcomes than surgical laparotomy.⁹³ Moreover, transarterial embolization is often used for pain relief, oncological palliation, and to decrease vascularity and tumor bulk before the surgical intervention.⁹⁴

If interventional capabilities are not available or the patient is hemodynamically unstable, exploratory laparotomy is the next step. Surgery is the definitive treatment for adrenocortical carcinoma and pheochromocytoma, and it should be considered in particular if the size of the mass is greater than 6 cm.¹⁰

Conclusion

Adrenal hemorrhage is a rare condition that can be caused by a variety of traumatic and non-traumatic conditions. Imaging modalities play a pivotal role in the diagnosis and management of adrenal hemorrhage. Imaging characteristics depend on the age of the hematoma and the presence of an underlying adrenal lesion. Radiologists should be familiar with the imaging features, differential considerations, and management options for adrenal hemorrhage.