P2904 - Severe Cholestasis as a Paraneoplastic Phenomenon Associated With Adrenocortical Carcinoma

Tuesday, October 26, 2021

10:30 AM – 4:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Award: Presidential Poster Award

Presenting Author(s)

Abdullah Muftah, MD

Baylor College of Medicine
Houston, TX, United States

Award: Presidential Poster Award

Abdullah Muftah, MD¹, Lan Wang, MD², Hao Chi Zhang, MD³
¹Baylor College of Medicine, Houston, TX; ²MD Anderson Cancer Center, Houston, TX; ³University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: Cholestasis with conjugated hyperbilirubinemia in patients with underlying malignancy bears a wide differential diagnosis including infiltrative disease, biliary obstruction, treatment-related toxicities, and, rarely, paraneoplastic effects. Adrenocortical carcinoma can have multiple systemic effects dependent on the type of hormone being secreted, but no related paraneoplastic jaundice or cholestatic liver disease is recorded. We report a case of cholestatic hepatitis related to a paraneoplastic effect secondary to adrenocortical carcinoma.

Case Description/Methods: A 38-year-old man with a history of alcohol use disorder in remission and hereditary spherocytosis was evaluated for new-onset intractable pruritus, jaundice, dark urine, and acholic stools. A 20-cm adrenal mass was identified on computed tomography (CT), concerning for adrenocortical carcinoma, due to elevated DHEAS, gynecomastia, and erectile dysfunction. Lab results showed total bilirubin of 8.7 mg/dL, direct bilirubin 7.0 mg/dL, ALT 79 U/L, alkaline phosphatase (ALP) 294 U/L, negative results for acute viral hepatitis, and elevated estradiol level. Autoimmune markers including anti-mitochondrial antibody were negative. Repeat abdominopelvic CT showed a 20.3-cm heterogeneously enhancing left suprarenal mass, without biliary ductal dilatation. Liver biopsy demonstrated non-specific cholestasis, bile duct injury, and canalicular bile plugs, without cirrhosis. Surgical resection was initially deferred. However, due to progressive deep jaundice, despite ursodiol, with a peak bilirubin of 29 mg/dL and concern for liver failure, the patient ultimately underwent urgent surgical resection (en bloc left adrenalectomy, left nephrectomy, and liver wedge resection). Post-operatively, hyperbilirubinemia resolved, and liver enzymes significantly improved, with clinical remission.

Discussion: Deep jaundice and severe cholestasis were attributed to paraneoplastic effects of an adrenocortical carcinoma due to their resolution after tumor resection. This specific context has yet to be described in the literature. Paraneoplastic cholestasis has been reported in renal cell carcinoma and non-Hodgkin’s lymphoma, but no hormones or antibodies have been identified. In this case, estradiol was elevated, and the tumor was secreting substantial amounts of DHEAS and metanephrines, but their relationship to inducing cholestasis remains unclear. Since conservative measures failed, surgical resection yielded successful definitive treatment in this case.

Figure: (A) and (B): Coronal and axial images from abdominopelvic computed tomography demonstrating a 20.3 cm x 16.5 cm x 18.8 cm heterogeneously enhancing mass in the left suprarenal region, not separate from the left adrenal gland, suspicious for the known large adrenal mass; the mass displaces the left kidney inferiorly; there is indentation of the left renal upper pole cortex and abutment of the anterior renal cortex by the mass without separate fat plane; the left renal vein is splayed along the inferior and medial aspect of the mass, and splenic vein is splayed along the superomedial aspect of the mass. (C) and (D): Parenchymal liver biopsy (H&E) histology demonstrating chronic cholestasis, canalicular bile plugs (arrows in Panel C), and bile ductular proliferation with bile duct injury (arrow in Panel D). (E) Chronological representation of the clinical course in relation to liver enzyme levels and the total bilirubin level before and after surgical management. (Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase)

Days from initial presentation	ALT (U/L)	AST (U/L)	ALP (U/L)	Total bilirubin (mg/dL)	Direct bilirubin (mg/dL)
-67	140	58	206	0.8	-
0	79	85	294	8.7	7.0
15	114	112	331	14.3	12.4
23	150	149	348	17.3	14.3
34	125	140	391	15.8	14.2
37	79	88	243	24.0	19.0
40	63	74	182	29.0	19.0
52	62	185	337	26.4	-
53	44	94	162	17.0	12.2
59	53	52	104	15.0	-
86	74	59	332	4.4	2.2
129	65	38	104	0.9	0.4

Table: Table delineating chronological liver biochemistry values in relation to time of initial clinical presentation of jaundice. Surgery (en bloc left adrenalectomy, left nephrectomy, and segment III wedge resection of liver) was performed on Day 53. (Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase)

Disclosures:

Abdullah Muftah indicated no relevant financial relationships.

Lan Wang indicated no relevant financial relationships.

Hao Chi Zhang indicated no relevant financial relationships.

Abdullah Muftah, MD¹, Lan Wang, MD², Hao Chi Zhang, MD³. P2904 - Severe Cholestasis as a Paraneoplastic Phenomenon Associated With Adrenocortical Carcinoma, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.