Adrenocortical carcinoma

Adrenal masses are often found on abdominal imaging studies that were performed to evaluate other diagnoses or nonspecific symptoms. Various opinions on the workup and treatment of these adrenal incidentalomas are readily found in the literature. We report a case of a young woman whose workup for symptoms of biliary colic led to the discovery of such a mass. The mass was found to be an adrenal cortical carcinoma with no evidence of lymphatic or capsular invasion.

Introduction

The decision about what to do with incidentally discovered adrenal masses is not an uncommon situation for today's surgeon. Over the last 20 years, multiple reports in the literature place the prevalence of adrenal incidentalomas on computed tomographic scans at 1 to 3%, which also correlates with autopsy studies. Many variables are present in each case that can guide the surgeon toward the best treatment option. Among these variables are: size, age, medical condition of the patient, appearance of the mass on imaging studies, and functional status of the mass. There are many algorithms that incorporate these different aspects into a flowchart that can provide a good framework for the initial evaluation of these patients.1 This case illustrates that significant adrenal pathology can exist in otherwise healthy young patients and the need for vigilant workup followed by appropriate intervention or observation.

Case Report

The surgery service was consulted for a 31-year-old female trainee with complaints of right upper quadrant pain and nausea. Her symptoms had started 2 weeks previously and had become progressively worse. She was unable to complete her training because of pain. She admitted to similar pain in the distant past, but she had not had pain for years. Initial laboratory values were unremarkable with a normal white blood cell count (8,300/mm^sup 3^) and normal liver function test. Calcifications were visible in the right upper quadrant on abdominal flat plate. Right upper quadrant ultrasound was obtained, which showed cholelithiasis with dilated intrahepatic ducts and a common bile duct that was dilated to the level of the ampulla vater (maximal dilation, 10.3 mm). These findings, as well as new scierai icterus on physical examination, prompted repeat liver function studies. The repeated studies 2 days later showed a bilirubin of 3.7 mg/dL, [gamma]-glutamyl transferase of 330 U/L, alanine aminotransferase of 991 U/L, and normal amylase and lipase. The radiologist recommended computed axial tomographic (CAT) scan to evaluate the head of the pancreas. The CAT scan showed cholelithiasis with intrahepatic and common bile duct dilation and a 7.0-cm solid mass in the left adrenal gland (Fig. 1). Gastroenterology was consulted for endoscopie retrograde cholangiopancreograghy. Endoscopic retrograde cholangiopancreograghy showed no stone or mass in the common bile duct or ampulla vater and normal pancreatogram. Plasma levels of aldosterone and renin were obtained revealing a slightly elevated renin level. Twenty-four-hour urine was collected showing normal catecholamines and metanephrines. Urinary cortisol and [alpha]-ketosteroids were elevated at 26.5 mg/24 hours and 197 mg/24 hours, respectively.

The patient was taken to the operating room, and the gallbladder and left adrenal mass were removed through an extended left subcostal incision. The adrenal mass was approached through the lesser sac by mobilizing the inferior border of the pancreatic body and tail. There was no local tumor invasion or lymph node involvement noted intraoperatively. Intravenous hydrocortisone was started as prophylaxis against Addisonian crisis. She did well postoperatively and was discharged from the hospital on the eighth postoperative day. Gross pathologic investigation revealed a 6.0 x 7.0 x 8.0-cm well-encapsulated solid mass. Some mitotic figures and pleomorphic nuclei were found on histologic examination, suggesting an adrenal cortical carcinoma (Fig. 2). No invasion was noted into the capsule.

The patient had recovered well and had no major complaints on follow-up examination 6 weeks later. A repeat CAT scan of the abdomen and pelvis showed no evidence of metastatic disease or recurrence. The oncologist recommended follow-up CAT scans every 3 to 6 months for at least 3 years. It was also the opinion of the oncologists that there was no benefit to adjuvant chemotherapy for preventing recurrence or metastasis. She was medically discharged from active duty with plans for continued care from her civilian private medical doctor.

Discussion

Adrenal incidentalomas are adrenal masses discovered on imaging studies performed for unrelated reasons. The prevalence of adrenal incidentalomas range from 1% to 4%.2 The differential diagnosis of these adrenal masses include: cortical adenomas, pheochromocytoma, aldosteronomas, metastatic lesions, adrenal cortical carcinomas, and a host of non-neoplastic lesions.3 Nonfunctioning adrenal cortical adenomas account for the majority of incidental masses. Adrenal cortical carcinomas are some of the rarest adrenal lesions.4

Clinical evaluation of adrenal masses always begins with history and physical examination. The majority of adrenal masses do not present with any clinical manifestation of hormone excess. Only 10% of masses exhibit evidence of hormone over activity. Patients who have these clinically evident adrenal masses may have vague signs and symptoms.1 Truncal obesity, hypertension, and diabetes can be seen in patients with adrenocortical tumors. Hypertension is a key feature in patients with aldosteronoma and pheochromocytoma.5

Surgically treatable causes of hypertension should be suspected in patients with acute onset of malignant hypertension and young patients found to have hypertension. A CAT scan is usually adequate for characterization of most adrenal masses, but magnetic resonance imaging or ultrasound may be helpful in selected cases. The CAT scan will accurately determine adrenal size as well as the presence of local invasion or metastatic spread.6

A variety of serum and urinary studies must be obtained before attempting resection of an adrenal incidentaloma. Preclinical Cushing's syndrome is a condition seen in patients with cortisol-secreting tumors but lack the physical signs of Cushing's syndrome. These patients usually have normal plasma concentrations and 24-hour urinary secretion of cortisol. A dexamethasone suppression test can be done to evaluate for the presence of this occult form of Cushing's syndrome. Patient's found to have preclinical Cushing's syndrome should be given prophylactic perioperative intravenous steroid therapy to prevent postoperative Addisonian crisis.4 Aldosteronoma is suspected in patients who present with hypertension and hypokalemia. Plasma aldosterone and renin levels should be obtained. Elevated aldoserone to renin ratio strongly suggests an aldosterone-secreting tumor.2 The possibility of a pheochromocytoma must be excluded in every patient who presents with an adrenal mass, even if the patient is normotensive. The biochemical investigation of these adrenal masses must also include: catecholamine, metanephrine, and vanillylmandelic acid levels drawn preoperatively. Twenty-four-hour urinary secretion of these substances provides the most sensitive quantification.7 The routine use of ^sup 131^I- metaiodobenzylguanidine scanning is advocated by many authors when there is biochemical evidence of a pheochromocytoma.2,3 When metastasis to the adrenal gland is suspected, fine needle aspiration (either CAT scan or ultrasound guided) can provide a tissue diagnosis, sparing the patient from an invasive procedure. However, pheochromocytoma must be ruled out before fine needle aspiration of the adrenal gland is attempted.4

Differentiating adrenal cortical adenoma from carcinoma is a very difficult task even for the pathologist. Size is an important factor since 90% of adrenal cortical carcinomas are greater than 6 cm in diameter.4 Elevated plasma levels of dehydroediandrostenedione are also associated with adrenal cortical carcinoma.6 In this case, a large left adrenal mass was discovered on CAT scan, and the mass was found to be an adrenal cortical carcinoma. Adrenal cortical carcinomas are rare lesions with an incidence of only two per million per year.8 The average 5-year survival for adrenal cortical carcinoma is 34%, with a mean survival time of 35 months for early stage lesions.9,10 Early stage lesions (stage I and stage II lesions) can theoretically be cured with surgery alone. Complete surgical resection of tumor remains the cornerstone of therapy, and need for adjuvant therapy for early stage lesions is controversial.11 Adjuvant therapy with Mitotane (1,1-dichlorodiphenyldichloroethane) has shown modest benefit but is most often used in the palliation of endocrine-related symptoms.12 Protocols using cisplatin-based regimen in combination with Mitotane are showing some promise; however, the prognosis for adrenal cortical carcinoma remains bleak.13 Our patient had stage II adrenocortical carcinoma (T^sub 2^N^sub 0^M^sub 0^, lesion >5 cm with no local or lymphatic invasion), and no adjuvant therapy was recommended by the oncologist. She will be followed for recurrence with serial CAT scans.

Acknowledgments

The authors thank David Lipsi, MD FACS, Barbara Tarsoly, RN OCN, MAJ Frederick Swiger, MC USA, MAJ Richard Cheng, MC USA, Stephen Leap, and George Mensch for their assistance in completing this manuscript.

References

1. Schteingart DE: Management approaches to adrenal incidentalomas: a view from Ann Arbor, Michigan. Endocrinol Metab Clin North Am 2000; 29: 127-39

2. Bertherat J, et al: Adrenal incidentalomas. Opin Oncol 2001; 14: 58-63.

3. Porcaro AB, Novella G, Curti P, et al: Adrenal incidentalomas: surgical treatment in 28 patients and update of the literature. Int Urol Nephol 2001; 32: 295-302.

4. Brunt LM, Moley JF: Adrenal incidentaloma. World J Surg 2001; 25: 905-13.

5. Linos DA: Management approaches to adrenal incidentalomas: a view from Athens, Greece. Endocrinol Metab Clin North Am 2000; 29: 141-58.

6. Murai M, Baba S, et al: Management of incidentally discovered adrenal masses. World J Urol 1999; 17: 9-14.

7. Patel HR, Harris AM, Lennard TW: Adrenal masses: investigation and management of adrenal incidentalomas. Ann R Coll Surg Engl 2001; 83: 250-1.

8. Schteingart DE: Conventional and novel strategies in the treatment of adrenocortical cancer. Braz J Med Biol Res 2000; 33: 1197-200.

9. Kopf D, Goretzi PE, Lehnert H: Clinical management of malignant adrenal tumors. J Cancer Res Clin Oncol 2001; 127: 143-55.

10. Dackiw AP, et al: Adrenal corlical carcinoma. World J Surg 2001; 25: 914-26.

11. Pommier RF, Brennan MF: An eleven-year experience with adrenocortical carcinoma. Surgery 1992; 112: 963-71.

12. Luton JP, et al: Clinical features of adrenocortical carcinoma, prognostic factors, and effect of mitotane therapy. N Engl J Med 1990; 332: 1195-201.

13. Williamson SK: Phase II evaluation of cisplatin and etoposide followed by mitotane at disease progression in patients with locally advanced or metastatic adrenocortical carcinoma: a Southwest Oncology Group study. Cancer 2000; 88: 1159-65.

Guarantor: MAJ Booker T. King, MC USA

Contributors: MAJ Booker T. King, MC USA; CPT Todd J. Lucas, MC USA

Moncrief Army Community Hospital, Surgery Clinic, 4500 Stuart Avenue, Fort Jackson, SC 29207.

This manuscript was received for review in May 2002. The revised manuscript was accepted for publication in August 2002.

Reprint & Copyright (C) by Association of Military Surgeons of U.S., 2003.

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