A giant non-functional adrenocortical carcinoma presenting with acute kidney injury
Yu-Chen Tseng . Seng-Tang Wu . Tai-Kuang Chao . Ching-Jiunn Wu . Tom Chau . Sung-Sen Yang
Received: 16 September 2013/ Accepted: 10 December 2013/Published online: 29 December 2013 @ Springer Science+Business Media Dordrecht 2013
Abstract Hormonally inactive adrenocortical carcinoma (ACC) is a rare disease where abdominal discomfort and back pain are common presenting symptoms due to mass effect from a large tumor. Acute kidney injury (AKI) from retroperitoneal tumors has rarely been reported. The most common etiologies include venous thrombosis, ureteral compression, or both. Here, we described a man who presented with AKI from a large retroperitoneal tumor, which was finally diagnosed as a non-functional ACC. The inferior vena cava (IVC) was nearly com- pletely compressed by the large retroperitoneal tumor leading to venous outflow obstruction and AKI. After surgical resection, his urine output increased and renal function recovered. Unfortunately, AKI recurred 2 months later due to recurrence of the tumor. Treatment with a tyrosine kinase inhibitor stabilized his tumor size, and hemodialysis was started. IVC-compression-
Electronic supplementary material The online version of this article (doi: 10.1007/s11255-013-0629-2) contains supplementary material, which is available to authorized users.
Y .- C. Tseng . S .- S. Yang Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec2, Cheng-gong Rd., Neihu District, Taipei 114, Taiwan, ROC
e-mail: sungsenyang@hotmail.com
S .- T. Wu
Division of Urology, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
T .- K. Chao Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
associated AKI can be the presenting scenario for ACC, a rare but prognostically important aggressive neoplasm.
Keywords Acute kidney injury . Adrenocortical carcinoma · Hemodialysis · Inferior vena cava
Abbreviations
ACC Adrenocortical carcinoma
AKI Acute kidney injury
CT Computed tomography
IVC Inferior vena cava MRI Magnetic resonance imaging
Introduction
With widespread use of computed tomography (CT) and magnetic resonance imaging (MRI), incidental adrenal masses are increasingly being found [1]. The majority are adrenocortical adenomas, while adrenocortical carcinomas
C .- J. Wu Division of Genitourinary, Department of Radiology,
Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
T. Chau Department of Medicine, Providence St. Vincent Medical Center, Portland, OR, USA
S .- S. Yang Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
(A)
(B)
>
| Unit | Reference range | ||
|---|---|---|---|
| Serum | |||
| ACTH | 51.5 | pg/ml | 0.1-46.0 |
| Cortisol | 15.58 | µg/dl | 5.0-23.0 |
| (06:00) | |||
| 17.09 | 3.0-16.0 | ||
| (16:00) | |||
| PRA | 1.37 | ng/ml/h | 0.15-2.33 (supine) |
| Aldosterone | 105.7 | pg/ml | 12-150 (supine) |
| Testosterone | 415 | ng/dl | 241-827 |
| Urine (catecholamines) | |||
| Dopamine | 20.9 (l) | ug/day | 138.0-540.0 |
| Norepinephrine | 4.8 (l) | µg/day | 10.0-80.0 |
| Epinephrine | <2.0 | µg/day | 0-20.0 |
| 17-OHCS (urine) | 2.7 (l) | mg/day | 5.0-23.0 |
| VMA (urine) | 3.9 | mg/day | 1.0-7.5 |
(ACC) are rare, with an estimated incidence of one to two new cases per million per year [2]. The age distribution of ACC is reportedly bimodal with a first peak in childhood and a second higher peak in the fourth to fifth decades of life [2].
It also seems to occur more frequently in women than in men (ratio 1.5:1) [2]. Patients present with evidence of excess adrenal hormones in approximately 60 % of cases, with Cushing’s syndrome being the most common presentation [3]. Other symptoms, depending on the effected hormone, include hirsutism, virilization, male pattern baldness, oli- gomenorrhea in females, and gynecomastia and testicular atrophy in males. In patients with hormonally inactive ACC, abdominal discomfort or back pain are common presenting symptoms due to mass effect from a large tumor [3].
Herein, we report on a man who presented with volume overload and acute kidney injury (AKI). Diag- nostic workup revealed a large right adrenal tumor compressing the inferior vena cava (IVC). The patient’s condition improved after surgical resection, and histo- logical examination revealed a well-differentiated ACC. However, recurrence of the giant tumor with IVC com- pression leads to recurrent AKI.
Case report
A 56-year-old man with a history of hepatitis B virus carrier, diet-controlled hypertension, and prediabetes
(A)
. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
(B)
(C)
presented to the emergency department with general mal- aise, shortness of breath, and decreased urination of 1-week duration. Upon arrival, his vital signs were temperature 37.0 ℃, blood pressure 150/93 mmHg, and pulse rate 88/min. Physical examination revealed pale conjunctiva,
diminished breath sounds and rales over bilateral lung fields, ovoid abdomen with hepatomegaly (4 fingertips below the lower rib at the mid-clavicular line), diffuse abdominal tympani to percussion, no lymphadenopathy, and pitting edema of the lower extremities. Blood tests revealed metabolic acidosis (pH 7.048; PaCO2 10.9; HCO3- 2.9 mmol/l), hyperkalemia (K+ 6.5 mmol/l), ele- vated liver transaminases (sGOT/sGPT 1,886/1,195 U/l), and renal insufficiency (BUN/Cr 147/14.6 mg/dl). The urine sediment was bland. The chest radiograph showed cardiomegaly and pulmonary trunk engorgement. He was diagnosed with AKI with electrolyte imbalances, metabolic acidosis, and pulmonary edema and underwent emergent hemodialysis. The abdominal ultrasound was negative for hydronephrosis but showed a 16-cm heteroechogenic lesion in the right upper abdomen. Due to the patient’s chronic hepatitis B carrier status, hepatocellular carcinoma was considered. CT of the abdomen revealed a huge lob- ulated mass over the right suprarenal region; the inferior vena cava and the right adrenal gland could not be clearly identified (Fig. 1a). Bilateral renal arteries were patent and free from tumor compression (Figure S1A). Because the mass may have arisen from the adrenal, he underwent hormone testing. All of his endocrine assessments were negative (Table 1). The patient underwent whole-body bone scan which revealed no metastatic lesions. Finally, the patient had an open adrenalectomy with en masse resection of a bulky adrenal tumor measuring 24 × 18 × 11 cm in size and weighed 1.49 kilograms (Fig. 2a). At surgery, the surgeon noted IVC wall attach- ment by the mass but no compression of either renal artery. Adrenal cortical carcinoma was diagnosed by pathological examination. Microscopically, tumor cells revealed a broad trabecular pattern with anastomosing cord of cells, marked nuclear anaplasia, a mitotic rate of more than 5 of per 50 high-power fields (Fig. 2b), and positive immunostaining for melan-A (Fig. 2c). The histopathologic findings and immunohistochemical stain were consistent with well-dif- ferentiated primary ACC. The surgical margins were free of tumor, and no lymphovascular invasion was identified. Thus, a diagnosis of stage III ACC (AJCC pT3cN0M0) was made. The patient then received salvage radiotherapy without obvious side effects. His physical function improved, as did his liver function (sGOT/sGPT 27/25 U/l) and renal function (BUN/Cr 21/2.5 mg/dl).
At his 2-months follow-up, his renal function was noted to be deteriorating (BUN/Cr 59/6.0 mg/dl) with a soft tis- sue bulge in his right lateral abdomen and progressive lower leg edema. MRI of the abdomen revealed another large lobulated mass in the right suprarenal space, highly suggestive of recurrent ACC, with the compression of the IVC superior to the anastomoses of the renal veins (Fig. 1b). Color Doppler renal ultrasonography showed
150
15
120
surgery
12
BUN (mg/dL)
90
9
Cr (mg/dL)
60
6
30
3
HD
HD
0
| 0 Day | 0 | 1 | 3 | 30 | 35 | 40 | 70 | 90 | 125 | 150 |
| BUN | 147 | 104 | 76 | 31 | 67 | 83 | 21 | 59 | 75 | 85 |
| Cr | 14.6 | 11.2 | 9.6 | 4.1 | 4.7 | 5.4 | 2.5 | 6 | 6.5 | 6.8 |
elevation of the resistive index in both kidneys (0.77, 0.85 in the right kidney and 0.90, 0.91 in the left kidney), suggesting poor intra-renal blood flow and prognosis for kidney function. Treatment with sunitinib, a tyrosine kinase inhibitor, has stabilized his general condition. A follow-up CT of the abdomen showed stable tumor size and bilateral renal arteries far from the ACC (Figure S1B). However, he continues on maintenance hemodialysis due to persistent renal insufficiency (Fig. 3).
Discussion
The size and appearance of retroperitoneal tumors on imaging give insight into their biologic behavior [4]. Tumors more than 6 cm in diameter, irregular borders, internal heterogeneity, and calcifications are risk predictors of malignancy and require appropriate management [4]. Our patient was noted to have a giant, heterogeneous, retroperitoneal tumor near 20 cm in diameter. It was dif- ficult to further characterize its location of origin and other features due to its tremendous size. Ultimately, surgical pathology made the diagnosis of non-functional ACC.
Overall, ACC is more frequently seen in females and present with an endocrine syndrome. Male patients tend to be older and have a worse prognosis. However, non-func- tional ACC is estimated to comprise <40 % of all cases, and its incidence is equally divided between the sexes [5, 6]. ACC is potentially lethal although timely adrenalec- tomy can improve survival [3]. Complete resection of ACC offers a chance for cure, although the rate of local recur- rence or distant metastasis is estimated to be more than 70 % [2, 5]. As far as we know, there is nothing in the literature regarding the timeframe of recurrence. Our patient appeared to have a particularly aggressive
neoplasm, as he recurred with another giant tumor only 2 months after his initial surgical resection. The rapidity of the tumor’s growth probably did not allow time for col- lateral vessels to form. Patients with non-functional or hormonally inactive ACC have protean clinical manifes- tations, such as abdominal fullness, indigestion, vomiting, and back pain. In these cases, the tumors are frequently more than 10 cm and exert mass effects [6]. The mass effect of the giant tumor in our patient manifested through kidney injury and its sequela.
The cause of AKI in cancer patients is often multi-fac- torial, but is clinically useful to classify among three mechanisms: prerenal, intrinsic, and postrenal [7]. Com- pared to intrinsic AKI, timely reversion of prerenal or postrenal causes usually results in recovery of function, but delayed correction can lead to long-term kidney damage [8]. There have only been a few reports of AKI secondary to retroperitoneal tumors or solid masses in the genitouri- nary system. These include (A) vascular invasion, such as renal artery/vein or IVC invasion/thrombosis [9-11]; (B) renal pelvis or ureteral compression or encasing [10, 12]; and (C) renal parenchyma metastases [13]. It has been reported that a patient with a giant left side non-functional ACC presented with varicocele and AKI after developing thrombus in the left renal vein and IVC [9]. In our patient, direct compression from a right-sided giant retroperitoneal mass caused near-total obstruction of the IVC, which lies right of midline. After tumor resection, his urine output and renal function recovered, only to worsen again, along with lower limb pitting edema, when the large tumor recurred 2 months later. The time course relating his pitting edema and renal function to his giant ACC highly suggests IVC compression as the cause of his AKI. Obstruction of the IVC is a well-recognized cause of decreased glomerular filtration rate and postrenal kidney injury, as in the present
case. In addition to CT or MRI, inferior vena cava venography may be used to confirm the diagnosis of IVC compression or encasement. To the best of our knowledge, this is the first reported case of AKI caused by IVC com- pression without thrombosis by a large retroperitoneal tumor.
Conclusions
In conclusion, ACC is a rare and usually aggressive, poor prognostic retroperitoneal tumor with frequent recurrence. Non-functional ACC with IVC compression presenting as AKI is uncommon, but prompt diagnosis and management of renal insufficiency is vital to both improving kidney function and supporting patients for further oncologic treatment. Clinician should be suspicious of retroperitoneal malignancies with IVC compression in patients with abdominal masses and AKI.
Conflict of interest None.
Consent Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.
References
1. Nieman LK (2010) Approach to the patient with an adrenal incidentaloma. J Clin Endocrinol Metab 95(9):4106-4113
2. Berruti A, Baudin E, Gelderblom H, Haak HR, Porpiglia F, Fassnacht M, Pentheroudakis G, Group EGW (2012) Adrenal
cancer: ESMO Clinical Practice Guidelines for diagnosis, treat- ment and follow-up. Ann Oncol 23(Suppl 7):vii131-vii138. doi: 10.1093/annonc/mds231
3. Allolio B, Fassnacht M (2006) Clinical review: adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab 91(6):2027- 2037
4. Boland GW, Blake MA, Hahn PF, Mayo-Smith WW (2008) Incidental adrenal lesions: principles, techniques, and algorithms for imaging characterization. Radiology 249(3):756-775
5. Phan AT (2007) Adrenal cortical carcinoma-review of current knowledge and treatment practices. Hematol Oncol Clin North Am 21 (3):489-507; viii-ix
6. Zini L, Porpiglia F, Fassnacht M (2011) Contemporary man- agement of adrenocortical carcinoma. Eur Urol 60(5):1055-1065
7. Humphreys BD, Soiffer RJ, Magee CC (2005) Renal failure associated with cancer and its treatment: an update. J Am Soc Nephrol 16(1):151-161
8. Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kel- lum JA, Liu KD, Mehta RL, Pannu N, Van Biesen W, Vanholder R (2013) Acute kidney injury: an increasing global concern. Lancet 382(9887):170-179
9. Cheungpasitporn W, Horne JM, Howarth CB (2011) Adreno- cortical carcinoma presenting as varicocele and renal vein thrombosis: a case report. J Med Case Rep 5:337
10. Gasparis AP, Kokkosis A, Labropoulos N, Tassiopoulos AK, Ricotta JJ (2009) Venous outflow obstruction with retroperitoneal Kaposi’s sarcoma and treatment with inferior vena cava stenting. Vasc Endovasc Surg 43(3):295-300
11. Gupta A, Pacha O, Skaria R, Huynh T, Truong L, Abdellatif A (2012) Retroperitoneal sarcoma presenting as acute renal failure, secondary to bilateral renal artery invasion. Clin Nephrol 78(2):164-168
12. Spector DA, Katz RS, Fuller H, Cristiano LM, Vitalis S, Jarrow J (1989) Acute non-dilating obstructive renal failure in a patient with AIDS. Am J Nephrol 9(2):129-132
13. Manning EC, Belenko MI, Frauenhoffer EE, Ahsan N (1996) Acute renal failure secondary to solid tumor renal metastases: case report and review of the literature. Am J Kidney Dis 27(2):284-291