Functioning and nonfunctioning cysts of the adrenal cortex and medulla

Functioning and

Medulla

Nonfunctioning Cysts of the Adrenal Cortex and

Gary P. Kearney, MD, Boston, Massachusetts

Edward M. Mahoney, MD, Boston, Massachusetts

Ellen Maher, MD, Boston, Massachusetts

J. Hartwell Harrison, MD, Boston, Massachusetts

This report reviews the literature and discusses briefly the etiology, pathology, clinical features, diagnosis, and management of cysts of the adrenal cortex and medulla. Eleven surgically proved cases of benign adrenal cysts seen in our institutions over

the past twenty years are analyzed and newer technics that aid in making a definitive diagnosis, espe-

cially differentiating the benign adrenal cyst from a malignant suprarenal mass, are emphasized.

Materials and Methods

Eleven patients (4 male, 7 female) with proved adrenal cysts were managed between 1951 and 1975. (Table I.) Surgical removal of the cyst was carried out in all patients and the pathologic specimen was reviewed. The ages ranged between twenty-seven and seventy-two years (mean, 50 years). Seven cysts occurred in the right adrenal and four in the left. There was a wide range of nonspecific constitutional symptoms. In those patients with large cysts, abdominal discomfort and gastrointestinal symptoms were common. Four patients had a palpable abdominal mass. Two of three patients (MB and GH) with cystic pheochromocytoma presented without characteristic symptoms of vasomotor instability such as flushing, restlessness, and sweating. Hypertension was present in four patients, and blood pressure reverted to within normal limits in two after operation (KW and PH). No renal vein renin studies were performed. Six of eleven patients showed the typical peripheral laminar calcification in a plain film (1 of 3 with cystic pheochromocytoma, 4 of 6 with fibrous wall pseudocysts, and 1 of 2 with hemorrhagic pseudocysts). There appears to be no relationship between the histopathologic features in the presence or absence of calcification.

On intravenous urography the kidney was displaced to a lower position in four and medially deviated in two, which

From the Department of Surgery, Division of Urology, Pet&w Bent Brigham Hospital, Harvard Medical School, and The Carney Hospital, Boston, Mas- sachusetts.

Reprint requests should be addressed to Gary P. Kearney. MO, 1101 Beacon Street, Brookline. Massachusetts 02146.

Read at the Annual Meeting of the American Urology Association, Las Vegas, Nevada, May 1976.

correlated well with large adrenal cysts. Ultrasonography was performed in two patients, and diagnosis was con- firmed in one (AB) by cyst puncture. Barium studies of the stomach and small bowel, gallbladder series, and liver scan were noncontributory when performed. In all patients studied by aortography and renal and adrenal arteriography and in one patient with adrenal venography, an avascular mass with stretching and splaying of vessels was noted. Two of three patients (GH and MB) with cystic pheochromocytomas had essentially negative biochemical determinations, including 24 hour urine for VMA, catecholamine, and metanephrines. No evidence of glucocorticoid excess could be demonstrated in any patient.

All patients were explored through either a transcostal eleventh rib extrapleural incision (5 patients), lumbar twelfth rib incision (5), or transabdominal incision (1). Complications encountered include two myocardial in- farctions, transient hydronephrosis which resolved, a wound infection, and intraoperative rupture of cyst without morbidity.

Pathologic examination revealed all specimens to be a variation of pseudocyst. There were three cystic pheochromocytoma and six fibrous wall and two hemorrhagic cysts within a normal gland. The sizes of the cysts ranged from 3 cm in diameter to one measuring 12 X 22 cm. (Table I.)

Clinical Aspects

Doran [I] described the first adrenal cyst found by Griselius from Vienna in 1670. A ruptured adrenal cyst was removed at autopsy in a forty-five year old male. Prior to 1947, only fifty cases of adrenal cysts had been recorded in the world literature [2]. In 1959, Abeshouse, Goldstein, and Abeshouse [3] reviewed the entire world literature and collected over 155 cases by autopsy (88) and operation (67). Foster [4] brought the total to 220 cases in 1966. Isolated case reports and our proved cases bring the total to approximately 250 [5].

Wahl [6] found an incidence of 0.06 per cent in a series of 14,000 autopsies. There appears to be equal frequency of occurrence on the right and left. Bilat- eral adrenal cysts have been reported, although

Volume 134, September 1977 363

Kearney et al

TABLE I Adrenal Pseudocysts

Patient Year Age (yr)/Sex Side Size(cm) Hypertension Pathology Complications

1. EKF 1950 53/F L 6 x 4.5 x 4.5 - Fibrous Cyst rupture 2. HS 1951 57/M L 7.5 x 5 + Fibrous

3. GH 1958 27/M R 8X8 - Pheochromocytoma Wound infection 4. AB [27]‘ 1959 49/M R 22x 12 - Fibrous 5. AF 1981 50/M R 5x5 + Fibrous

6. KW 1987 48/F R 13 x 10 + Pheochromocytoma Myocardial infarction;

7. MJ 8. PH

1988 29/F 1968 42/F

pneumonia R 18 X 13 Hemorrhagic Hydronephrosis L 6X6 Fibrous Mvocardial infarction

9. cat 1972 68/F L 9 X 8.2 X 5 - 10. MB 1975 72/F R 5x4 11. AD 1975 64/F R 9X8X5

Note: Our thanks to A. A. Borsky’ and J. Todd+ for contributing these cases.

Hemorrhagic Pheochromocytoma Fibrous

rarely, and most commonly in children [5,7]. Women are affected more often than men, at a rate of two to one, with all age groups being reported. Peak incidence appears between the third and the fifth decade [8]. Adrenal cysts may be unilocular or multilocular, ranging in size from microscopic to those containing several liters of fluid [9]. There is no agreement re- garding the etiology of this disorder. We prefer the following classifications proposed by Terrier and Lecene [IO] in 1906 and modified by Abeshouse, Goldstein, and Abeshouse [3] and Barron and Em- anuel [II]. (The percentages in each category indicate the occurrence as demonstrated in the analysis of 155 cases by Abeshouse, Goldstein, and Abeshouse

131.1

small cysts are multiple, vary from 1 to 15 mm in diameter, and contain clear or milky fluid, possessing a smooth, flattened endothelial lining as opposed to the proliferating endothelium of lymphangiomatous tumors. Conversely, they may attain massive pro- portions. The angiomatous cysts are believed to arise from dilated capillaries or sinusoids between columns of adrenal cells.

Parasitic cysts (7per cent) are quite rare. They are usually a part of a generalized disease process and are incidental findings at autopsy. These cysts are thick-walled, with or without calcification, and have parasites demonstrable within the wall of the cyst.

Epithelial cysts (9 per cent) are most commonly cystic adenomas. The degeneration within these adenomas is generally minimal or of moderate de- gree. Occasionally a cyst of this type may attain considerable size, and it may be difficult to distinguish this group from the pseudocyst formation, secondary to hemorrhage and necrosis within the adenoma. True glandular retention cysts are believed to be a misnomer by many, as adrenal cells form no true acini within a central lumen from which a fol- licular cyst could develop.

Pseudocysts (39per cent) are the most commonly recognized group of adrenal cyst found at exploration. All eleven in our series were of this group. They are generally small to moderate in size, containing a thick, reddish-brown fluid, with a regular pigmented lining without an endothelial wall. The dense fibrous wall frequently contains areas of calcification and may be hyalinized. Hemorrhage is postulated to occur within a normal or a pathologic gland such as pheochromocytoma, with extravasation, liquifaction, absorption, and encapsulation forming a thick fibrous wall. Adrenal hemorrhage has been reported in association with birth trauma and hemorrhagic disease of the newborn [12] as well as a wide variety of other pathologic conditions such as acute trauma, crush injuries, burns, shock, toxemia of pregnancy, syphilis, leukemia, and incompatible blood transfu- sions. The ability to develop degenerative necrosis with cyst formation within tumors, benign and malignant, with or without endocrine function, is a principal concern to the practicing urologist.

Endothelial cysts (45 per cent), the most common variety of all adrenal cysts, comprise two groups: lymphangiomatous and angiomatous. Lymphan- giomatous cysts (42 per cent) are far more frequently encountered than angiomatous cysts (3 per cent). The lymphatic group is either secondary to faulty development, lymphangiectasis of minute lymph spaces, or cystic degeneration of a hamartoma. The

The vast majority of adrenal cysts are asymptomatic because of their small size. Symptoms occur with large cysts because of displacement of normal organs. A dull, localizing lumbar pain may be present; vague gastrointestinal symptoms may occur such as gastric distress, eructation, occasional nausea, and vomiting, related to compression and displacement of bowel contents and liver. A palpable abdominal mass may be present when cysts are of massive pro- portions.

364 The American Journal of Surgery

Cysts of Adrenal Cortex and Medulla

Brindley and Chisholm [13] reported on two patients with clinical features of Cushing’s syndrome who at adrenalectomy were found to have benign adrenal cysts. Thbre have been no reports of patients with adrenal cysts who appeared normal and were found to have chemical evidence of glucocorticoid hypersecretion. Spontaneous remission of hypertension following cyst removal does occur (PH). The reason for this remains unclear. Renal vein renin studies have not been performed; it has been postulated that pressure on the renal vein from an ob- structing adrenal cyst may cause local renal ischemia with release of pressor substances [7]. All patients with adrenal cysts should be questioned for findings suggestive of an intermittently secreting pheochromocytoma, with or without hypertension.

Diagnosis

Distinguishing the malignant suprarenal mass from the benign adrenal cyst is an important re- sponsibility. Studies that help in this regard include plain abdominal films, nephrotomography, ultrasonography, aortography with renal and adrenal arteriography and venography, selective biochemical. studies, and occasionally gastrointestinal studies, oral cholecystography and liver scan. The differential diagnoses include cysts of the liver, spleen, pancreas and mesentery, benign and malignant tumors of the kidney and adrenal, aneurysms of the aorta and iliac, celiac, and splenic arteries, pathologic lymph nodes, hydronephrosis of an upper renal segment, gastric fundus, hepatosplenomegaly, and hydrops of the gallbladder.

Plain film of the abdomen may be helpful, especially in the presence of peripheral or eggshell calci- fications. [14]. (Figure 1A.) Six of our eleven patients with adrenal pseudocysts demonstrated this finding. Intravenous pyelography with nephrotomograms and oblique views should distinguish the adrenal mass to be separate from the kidney. When the cyst is large, the kidney will generally be displaced inferiorly with medial deviation. Ultrasound examination of the suprarenal area is a benign, noninvasive procedure that may give a clue as to the contents of the mass. A cyst containing clear fluid would be echo-free (Figure 2B); a nonhomogeneous cyst should produce a com- plex pattern as distinct from the solid pattern of most adrenal and renal tumors.

Aortography with selective renal and adrenal arteriography and venography can be of great help. Adrenal arteriography may demonstrate tumor vessels in an adrenal carcinoma, whereas stretching and bowing of arteries over an avascular mass

suggests the presence of a cyst. (Figure 2C.) The variability of adrenal arterial blood supply makes catheterization of the appropriate feeding adrenal branch difficult and delineation sometimes impos- sible. The value of this technic is closely related to the skill of the arteriographer performing the study.

Adrenal venography can be quite useful and accurate in the delineation of adrenal disorders [15,16]. Generally, a single central vein drains the right adrenal vein into the inferior vena cava, and the left adrenal vein into the corresponding renal vein. Catheterization of these veins is technically more difficult on the right side because of variability in position and shortness of the adrenal vein. Retro- grade venography can provide excellent architectural delineation of the entire gland, even with lesions less than 1 cm in size. This technic has been used in the differentiation of adrenal hyperplasia, aldosteronoma and cortical adenoma, adrenal carcinoma, and pheochromocytoma. Adrenal venography, however, has been associated with significant complications, including infarction of the adrenal gland, and for this reason is not always recommended [17,18].

Selective biochemical studies should be carried out to identify a cystic pheochromocytoma and functioning adrenal carcinoma and to rule out the presence of glucocorticoid excess or deficiency. Morning and afternoon cortisol determinations will assess diurnal variation. Overnight dexamethasone suppression test will rule out autonomous secretions in borderline cases. Multiple urinary biochemical determinations of VMA, metanephrine, and catecholamine should be performed. A glucagon stimulation test can be carried out in patients with high index of clinical suspicion and, when positive, indicates a pheochromocytoma, as false-positive results have not been reported [19]. Despite negative urinary determinations for pheochromocytoma, nitroprusside or phentolamine (Regitine@) in addition to propranolol (Inderal@) should be available for parenteral use during arteriography and surgical exploration in the event that a functioning tumor is encountered (case I). Upper gastrointestinal series, liver scan, barium enema, and gallbladder series in the presence of large adrenal cysts may demonstrate bowel and liver displacement, as well as rule out gallbladder disease. Retroperitoneal air insufflation is of historic interest and endoscopic procedures, including retrograde pyelography, are generally noncontributory but may reveal deviation of the ureter if the collecting system has not been adequately defined by standard intravenous urography. In children, vena cavography with simultaneous intravenous urography may be performed through a saphenous vein cannulation. In the

V0lumeJ134,s4pt~r1877 365

Kearney et al

Figure 1. A, intravenous pyelogram showing peripheral calciiication, primarily upper and lower pole, with displacement of the kidney. 6, selective renal arterlogram demonstrating relationship of the kidney separate from avascular suprarenal mass. C, left selective lumbar arteriogram without neovascularity demonstrated.

neonatal period, a patent umbilical artery may provide access for these studies. Cystic masses in children can frequently be transilluminated with high intensity fiberoptic light source.

Two cases are presented to illustrate clinical features and diagnostic approach. Case I illustrates the clinical silence of a cystic pheochromocytoma despite careful preoperative evaluation and case II illustrates typical calcification in adrenal pseudocyst as well as the displacement of the kidney.

Case I. MB, a seventy-two year old female, was referred for dysuria and nocturia. At age thirty-three years she underwent anterior colporrhaphy, followed by a second recent repair including vaginal hysterectomy. A suprapubic cystostomy was placed during surgery and the bladder left on drainage. On removal of the suprapubic tube, she con- tinued to have symptoms of urgency, frequency, and left suprapubic discomfort. Her urinalysis revealed microscopic hematuria, and her cultures were negative. There was a history of occasional weakness and anxiety of one month’s duration, especially on awakening. She denies palpitations, angina, claudication, flushing, or history of hypertension. Physical examination revealed a healthy-appearing elderly female. Her blood pressure ranged from 118 to 130 systolic over 80 to 90 diastolic. Cardiac examination revealed a grade II systolic ejection murmur consistent with mild mitral insufficiency. Her abdominal examination revealed no masses and a 1 cm cystotomy scar, which was well healed. Pelvic examination was unremarkable. Urinalysis revealed a few red cells per high-powered field. Laboratory data included an intravenous pyelogram, which revealed a right suprarenal mass measuring approximately 3 cm in diameter. (Figure 2A.) Twenty-four hour urinary VMA was 5.39,5.4, and 10.6 mg per 24 hours (normal, less than 10). Multiple 24 hour urinary metanephrine and catecholamine determinations were normal. Plasma AM and PM cortisol levels revealed normal diurnal variation and, with 1 mg dexamethasone administered at midnight, revealed normal

suppression without evidence of autonomous secretion. Adrenocorticotropic hormone stimulation, 80 units given parenterally, revealed a normal fourfold increase. Complete blood count and renal function studies were normal. B- mode ultrasound examination of the right kidney and suprarenal area with longitudinal and transverse scan de- lineated a 2.5 X 3 cm homogeneous cystic anechoic suprarenal mass. (Figure 2B.) Aortography with selective right middle adrenal arteriography revealed a thick-walled avascular mass. (Figure 2C.) Observation cystoscopy for microscopic hematuria was negative. On September 30, 1975, the patient was taken to the operating room for right adrenal exploration, with anesthesia preparation for an occult pheochromocytoma. A right adrenalectomy was carried out via eleventh rib extrapleural incision. During surgery, hypertension developed when the right adrenal mass was approached, and blood pressure increased to 180/110 and spontaneously resolved on removal of the adrenal gland. With intravascular expansion, no postoperative hypotension was encountered and her course was unremarkable. Pathologic examination revealed a 4 cm cystic pheochromocytoma. This most likely represented cystic degeneration with pseudocyst formation rather than true epithelial cystic adenoma. The patient has remained asymptomatic since surgery and has lost her mild symptoms of nervousness and fatigue.

Case II. AD, a sixty-four year old female, had dull left flank pain of seven years’ duration. She had urinary frequency secondary to ingestion of Lasix@, taken for peripheral edema without hypertension. She denied sweats, vasomotor symptoms, and headaches. A screening intravenous pyelogram proved abnormal. Past medical history included a tonsillectomy and appendectomy. Physical examination revealed a healty-appearing middle-aged woman. Her blood pressure was 130/80. There were no positive findings such as a palpable abdominal mass. Laboratory data included blood count and renal function studies within normal limits. Determination of urinary

366 The American Journal of Surgery

Figure 2. A, nephrotomogram revealing right upper pole mass, approximately 3 cm in diameter. B, B-mode nephrosonogram, Iongttudinal scan, 3 cm suprarenal cystic anechoic mass. C, selective right middle adrenal arteriogram demonstrating avascular 3 cm right adrenal mass.

metanephrine, catecholamine, VMA, and 17-hydroxy and ketosteroids were, within normal limits. Plain film of the abdomen revealed a calcified suprarenal mass measuring 9 X 8 X 5 cm. Intravenous pyelography revealed a normal right kidney and collecting system. The left kidney was displaced inferiorly and medially by a large suprarenal mass. (Figure IA.) Abdominal aortography and selective left renal angiography revealed displacement of the renal artery and kidney inferiorly and medially. The mass appeared to be separate from the kidney. Selective injection of the renal artery revealed a normal-appearing left kidney without neovascularity. (Figure 1B.) Selective injection of the third lumbar artery was performed and no abnormal vascularity was noted (Figure 1C); the adrenal vessels could not be cannulated. The patient was explored through a twelfth rib incision, and the adrenal and suprarenal mass was removed in its entirety without complication. Patho- logic examination revealed a fibrous wall cyst containing necrotic material consistent with organized hematoma. No tumor was found and her postoperative course was un- complicated.

Management

Surgical exploration is recommended for accurate diagnosis in almost all patients. The possibility of a malignant or functioning tumor is real, and the burden of proof is with the surgeon. Surgery is fur- ther indicated for the relief of pressure symptoms or when related to hypertension. In selected poor risk patients in whom studies indicate a high level of confidence in the diagnosis of adrenal cyst, conser- vative management may occasionally be warranted. No case in the literature could be found in which a malignant tumor arose from the wall of an adrenal cyst.

The operative goal is complete removal of the cyst with preservation of the kidney and, if possible, the remaining adrenal gland. Various approaches, including transabdominal, combined lumbar and transperitoneal lumbar, with or without rib incision,

Volume 134, September 1977

and transthoracic technics have been utilized. We prefer the extrapleural, extraperitoneal flank incision in small cysts, and the transabdominal approach for larger ones. Surgery should be planned to provide adequate and safe exposure, depending on the size and location of the lesion. Great care must be taken on removal of the cyst wall, for it has been described to be adherent to diaphragm, vertebrae, vena cava, kidney, aorta, and large bowel. With a difficult dissection, evacuation of the contents of the cyst with marsupialization rather than total excision is a wise alternative. In children, the possibility of bilateral involvement should be investigated. During surgery preservation of what remaining adrenal gland exists is even more important to avert adrenal insufficiency if bilateral disease is present. In children hydronephrosis, Wilm’s tumor, and less often neuroblastoma are more common than benign adrenal cysts, as only sixteen cases have been reported in the world literature [5].

Summary

Adrenal cysts are rare clinical and pathologic en- tities. The vast majority are minute in size, unilateral, and found in females at autopsy. They come to the physician’s attention when they produce symptoms or are identified on x-ray studies. When symptom- atic, they generally produce lumbar discomfort and gastrointestinal symptoms, and occasionally are palpable by abdominal examination. There is no significant agreement as to cause and pathogenesis of the disease. The most common histologic types are lymphangiomatous endothelial cysts, secondary to lymphangiectasis, and the fibrous wall or hemorrhagic pseudocysts. In many patients preoperative diagnosis is now possible with high quality nephrotomography, ultrasonography, and adrenal arteriography. The presence of a suprarenal mass with

367

Kearney et al

peripheral or laminar calcification strongly suggests the presence of an adrenal pseudocyst. Selective biochemical studies are mandatory to rule out the presence of an occult cystic pheochromocytoma, and adrenal cortical tumor. Adrenal cysts must be dif- ferentiated from all space-occupying lesions of the upper abdomen. Surgical exploration is recommended in almost all patients for accurate diagnosis and to rule out malignant disease or occult pheochromocytoma. The choice of the surgical approach should be planned to provide for safe and adequate exposure, depending on the size and location of the lesion. Careful dissection with preservation of the adjacent kidney, liver, and pancreas should be performed.

References

1. Doran AHG: Cystic tumor of the suprarenal body successfully removed by operation. Br MedJ 1: 558, 1903.

2. Stock FE: Cysts of the adrenal gland. Posfgmd Med 23: 530, 1947.

3. Abeshouse GA, Goldstein RB, Abeshouse BS: Adrenal cysts: review of the literature and report of three cases. J (ho/ 81: 711,1959.

4. Foster DG: Adrenal cysts. Arch Surg 92: 131, 1966.

5. Wilson JM. Woodhead EM, Smith RD: Adrenal cysts; diagnosis and management. Urology 4: 248,1974.

6. Wahl HR: Adrenal cysts. Am J Pathol27: 758, 1951. 7. Lynn RB: Cystic lymphangioma of the adrenal associated with

areterlal hypertension. Can J Surg 8: 92, 1965. 8. Campbell M: Pedlatrlc Urology, vol 2. New York, McMillan,

1937, p 291. 9. Esquivel FE Jr, &abstald H: Giant adrenal cysts. J @v/94: 635,

1965. 10. Terrier F, Lecene: The large adrenal cyst. Rev Chir Paris 34:

321, 1906. 11. Barron SH, Emanuel B: Adrenal cysts: case reports and review

of pediatric literature. J Pediatr 59: 592, 1961. 12. Zupkner J: Adrenal cysts. Arch Path01 50: 468, 1950. 13. Brlndley GV, Chisholm JB: Cystic tumors of the adrenal gland

associated with Cushing’s syndrome. Texas J h&d 47: 234, 1951.

14. Palubinskas AJ, Christensen WR, Harrison JH, Sosman MC: Calcified adrenal cyst. Am J Roentgenol Radium Ther Nucl A&d 82: 853, 1959.

15. Mikaielsson EG: Retrograde phlebography of both adrenal veins. Acta Radio/ 348, 1967.

16. Reuter SR, Blair JA, Schteingart DE, Bookstein J: Adrenal venography. Radiology 89: 805. 1967.

17. Bayliss RIS, Edwards OM, Starer F: Complications of adrenal venography. Br J Radio1 43: 53 1, 1970.

18. Sllen W: Editorial comments, p 360. Yearbook of Surgery. Chicago, Year Book Medical, 1971.

19. Lawrence AM: Glucagon provocative test for pheochromocytoma. Ann Intern Med 66: 109, 1967.

21. Borsky AA: Case report. Medical Bulletin. United States Army, Europe 23: 294. 1966.

The Amarlcan Journal of Surgwy

Documents

Functioning and nonfunctioning cysts of the adrenal cortex and medulla