Hemorrhage in Bilateral Adrenal Metastases: A Unique Presentation of Non-Small Cell Lung Cancer

A 63-year-old man was admitted to the emergency department with left flank pain radiating into his chest. He had initially presented to an outside hospital and was transferred after 24 hours of observation and trending of the patient’s complete blood count, which remained stable.

History. The patient had a past medical history significant for chronic obstructive pulmonary disorder, significant tobacco use (45 pack-years), hypertension, and benign prostatic hyperplasia. His family history was significant for colon cancer in his father, who died at age 52 years, and brain cancer in his mother, who died at age 57 years.

His vital signs were stable on admission and his laboratory work, including hemoglobin, was unremarkable (Table).

Diagnostic testing. The computed tomography (CT) angiography aortic dissection protocol revealed a lobulated 3 cm mass with irregular margins in the right lung with an enlarged right hilar lymph node (Figure 1), which was not seen on a prior CT scan of the chest taken 3 years earlier. Additionally, a 6.6 x 3.6 cm heterogeneously hyperdense mass with irregular margins in the left adrenal gland was observed (Figures 2 & 3), along with a new 1.7 x 1.2 cm nodularity on the right adrenal gland not seen on previous imaging. The left adrenal mass had surrounding fat stranding and haziness due to hemorrhage. A non-contrast head CT showed no acute intracranial abnormality.

Figure 1. Lobulated mass with irregular margins in right lung (yellow star) causing narrowing of the right main bronchus with enlarged lymph node in right hilum (yellow arrow).

Figure 2. Non-contrast portion of the aortic dissection protocol CT scans showing a heterogenous lesion (yellow star) in the left adrenal gland which is predominantly hyperdense, suggestive of hemorrhage. Surrounding fat stranding and haziness is also seen (yellow arrow).

Figure 3. Heterogenous hemorrhagic mass involving the left adrenal gland (yellow star) with surrounding hemorrhage (yellow arrow) on CT aortic dissection protocol.

Differential diagnoses. The differential for the large left adrenal mass included adrenal metastasis, adrenocortical carcinoma (ACC), pheochromocytoma, adenoma, and adrenal hemorrhage.

An ACC was considered unlikely due to several factors such as the interval development over 3 years and a lack of calcifications. The adrenal masses did not have the degree of hypervascularity that would be seen in a classical pheochromocytoma as this case had 37 Hounsfield units (HU), whereas pheochromocytoma would be expected to be 110-120 HU. The large size of the left adrenal mass, heterogenous appearance, and density above 10 HU on unenhanced images excluded possibility of an adenoma. Concomitant presence of a new suspicious appearing lung mass and this being a new lesion from the 3-year-old prior scan made a hemorrhaging metastatic lesion the most likely possibility.

Treatment and management. The patient was discharged home with pain management and an outpatient follow-up was scheduled, which included an MRI of the abdomen for a potential interventional radiology biopsy, follow-up with a pulmonology specialist, positron emission tomography scans, and pulmonary function tests.

However, he presented again a week later, this time with right-sided flank pain and back pain described as identical to the previous encounter. A repeat CT scan of the abdomen and pelvis showed significant interval enlargement of the right adrenal gland, now 5.8 x 3.3 cm, a component of which was likely hemorrhage due to the density and surrounding fat stranding and haziness (Figure 4). The mass on the left had grown to 7.4 x 4.3 cm with some interval resolution of the bleeding.

Figure 4. Repeat scans taken 7 days later shows interval significant enlargement of right adrenal gland (yellow star) due to hemorrhage. There is hemorrhagic fluid between the liver and right adrenal gland (yellow arrow). Only a small mass lesion was seen on the right adrenal gland on the initial CT.

Pulmonology and oncology specialists were consulted. An endobronchial ultrasound was performed which showed tumor compression of the bronchus intermedius. A biopsy was obtained, and pathology showed a poorly differentiated non-small cell lung carcinoma. The patient was diagnosed with severe bilateral adrenal hemorrhages caused by metastatic lesions to the adrenal glands from a primary lung tumor.

Outcome and follow-up. Staging imaging was completed and biopsy results were finalized, which showed non-small cell lung cancer stage IV. The patient transitioned care to another facility where he completed 2 cycles of carboplatin, pemetrexed, and pembrolizumab. The pembrolizumab was then discontinued due to colitis. The patient completed a 3rd cycle of carboplatin and pemetrexed and received 2000 cGy in 5 fractions of 400 cGy/fraction via volumetric modulated arc therapy (VMAT) with imaging guidance.

Discussion. Non-traumatic adrenal hemorrhage is a rare phenomenon that can be caused by several factors, including coagulopathies such as disseminated intravascular coagulation, Waterhouse-Friderichsen syndrome caused by bacterial infection, adrenal neoplasm, and sepsis.^1,2,3 These conditions can cause massive retroperitoneal hemorrhage from the adrenal glands, which can cause life threatening adrenal insufficiency. Clinical features of adrenal hemorrhage include a sudden, precipitous drop in hematocrit, electrolyte imbalances, fever, and abdominal and flank pain.⁴ Aside from the abdominal and flank pain, none of these findings were seen in this case. The patient also had no evidence of coagulopathy or sepsis based on laboratory studies or vitals.

Waterhouse-Friderichsen syndrome is commonly caused by meningococcemia, for which this patient had no clinical evidence to suggest this as the cause of adrenal hemorrhage.³ Given the concomitant new mass in his lung, the most likely cause of this patient’s adrenal hemorrhage was determined to be hemorrhagic metastases from a primary lung tumor. Further studies of this patient with non-contrast head CT and brain magnetic resonance imaging with and without contrast showed no evidence of intracranial metastasis.

Primary adrenal masses or secondary metastasis can cause hemorrhage into the retroperitoneum. Commonly seen adrenal masses include pheochromocytoma, adrenocortical carcinoma, benign adenoma, and metastatic lesions.⁵ Adenomas are usually small (< 3 cm), homogeneous, and low density on CT due to high lipid content.⁵ ACC is an aggressive primary adrenal tumor that is often seen to be heterogenous and calcified on CT, with peripheral contrast enhancement.⁶ Pheochromocytoma is often seen to enhance avidly with contrast on CT.⁷ The adrenal masses in this case did not have these features making these diagnoses unlikely.

Both pheochromocytoma and ACC are more likely to present as unilateral masses than as bilateral masses. Pheochromocytoma, which normally presents as a slow growing, unilateral mass, was also unlikely given the presence of hemorrhage and absence of intense enhancement.⁷ While ACC can be extremely fast growing, especially when in association with multiple endocrine neoplasia type 1,⁸ these lesions were deemed more likely to be metastatic disease from the lung, considering the biopsy-proven presence of non-small cell lung cancer, bilateral adrenal lesions not previously seen on imaging 3 years prior, and hemorrhage.

The adrenal glands are a common site of metastases, with lung and breast cancers being the most common, followed by melanoma, stomach, and colon cancer.^9,10 While a common site of metastasis, clinical signs of adrenal metastatic disease are quite rare, and often only present when significant portions of the gland have been destroyed.^9,10

While metastases to the adrenal glands have been frequently found from a variety of neoplastic diseases – such as lung, stomach, and breast cancers, as well as melanoma –they are often only noticed incidentally and are rarely seen to cause clinically significant disease.¹⁰ Hemorrhage can also be seen in ACC, but hemorrhage from ACC is often small.⁶ While there is evidence of lung cancers metastasizing to the adrenal glands and idiopathic bilateral adrenal hemorrhage has been reported, bilateral hemorrhagic adrenal metastases are quite a rare phenomenon.^11,12,13

Conclusion. Hemorrhage from adrenal metastases secondary to primary lung tumors are uncommon. Bilateral hemorrhagic adrenal metastases from primary lung cancer are an even rarer phenomenon. Here we present a case of a patient presenting with bilateral adrenal hemorrhages occurring a week apart because of metastases from stage IV non-small cell lung cancer.

AFFILIATIONS:
¹Marian University College of Osteopathic Medicine, Indianapolis, IN
²Department of Radiology, MetroHealth Medical Center, Cleveland, OH

CITATION:
Tatineni V, Baughman WC, O’Connell K, Jain V. Hemorrhage in bilateral adrenal metastases: a unique presentation of non-small cell lung cancer. Consultant. 2023;63(7):e5. doi:10.25270/con.2023.06.000004.
Received October 19, 2022. Accepted February 21, 2023. Published online June 29, 2023.

DISCLOSURES:
The authors report no relevant financial relationships.

ACKNOWLEDGEMENTS:
None.

CORRESPONDENCE:
Vivekanand Tatineni, Marian University College of Osteopathic Medicine, 3200 Cold Spring Road, Indianapolis, IN 46222 (vtatineni010@marian.edu)

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