Urologia Internationalis
Original Paper
Urol Int 2006;77:173-178 DOI: 10.1159/000093915
Received: November 7, 2005 Accepted after revision: February 10, 2006
Indications and Results of Surgery for Incidentally Found Adrenal Tumors
A. Meyerª M. Behrendb
ªKlinik für Strahlentherapie und spezielle Onkologie, Medizinische Hochschule Hannover, Hannover, und
b Klinik für Viszeral-, Thorax-, Gefäss- und Kinderchirurgie, Klinikum Deggendorf, Deggendorf, Deutschland
Key Words
Adrenalectomy . Incidentally found adrenal tumors . Adrenal incidentaloma
Abstract
Introduction: The accidental discovery of an adrenal mass called incidentaloma has become an increasingly frequent clinical problem with the question of a correct and appropriate therapeutic approach being the subject of controversial discussions. Materials and Methods: Clinical charts of 52 patients (22 male, 30 female) who underwent adrenalectomy for an incidentaloma at our institution between 1987 and 2001 were reviewed. Re- sults: Median age was 56.4 years. Reasons for surgery were unclear significance in 22 patients, suspicion of ma- lignancy in 5, increase in size in 8, maximum tumor di- ameter of more than 5 cm in 7, fear of malignancy in 1, and subclinical secretion of cortisol in 5 patients. No data were available for 4 patients. Surgical resection was per- formed using a conventional transabdominal approach in 28 patients, a conventional dorsal approach in 17 pa- tients, and an endoscopic retroperitoneal approach in 7 patients. Histopathologic examination ruled out adrenal adenoma in 32 patients, adrenal myelolipoma in 12, uni- lateral nodular hyperplasia in 4, cystic lesion in 3, and adrenocortical carcinoma in 1 patient. The mean size of all lesions was 5.5 cm. Evaluating the criteria for surgical treatment regarding age of the patients and size of the lesions, 25 patients (48%), including the patient with the
adrenocortical carcinoma, were younger than 60 years and had an adrenal lesion exceeding 4 cm in size. During postoperative follow-up that was available for 39 pa- tients, 3 developed contralateral tumors that were treat- ed by resection in 1 and by close follow-up in 2. Conclu- sions: Size should not be the sole criterion; treatment should be tailored to the individual patient. Especially in patients younger than 60 years with an adrenal lesion exceeding 4 cm in size, an adrenalectomy, predominant- ly via an endoscopic approach, should be carried out, because a repeated and life-long close follow-up of an anxious patient who has been informed of the diagnosis will in some cases exceed the cost of a single endoscop- ic operation. Copyright @ 2006 S. Karger AG, Basel
Introduction
Adrenal nodules have been recognized for decades, with an overall frequency of approximately 6% in autop- sy studies [1-3]. With the increasingly widespread use of highly sensitive imagery with improved image resolution, the accidental detection of an incidentaloma defined as ‘clinically silent masses discovered incidentally during imaging procedures performed for unrelated nonadrenal problems’ has become a frequent clinical problem [4-7]. Based on autopsy studies, adrenal masses belong to the most common tumors in humans. Adrenal lesions can be found in up to 3% of all computed tomography (CT) scans
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of the thorax or abdomen [4-8]. The clinical problems involving incidentaloma are reflected in the worldwide proliferation of literature over the past decades. The cor- rect and appropriate therapeutic approach in the case of solid adrenal incidentalomas is still being debated and is a controversial topic of discussion. Although several stud- ies have been carried out regarding the diagnosis of adre- nal incidentalomas, various differing diagnostic and ther- apeutic strategies have been recommended to date. Un- fortunately, controlled studies concerning correct and cost-effective diagnostic evaluation and treatment are still lacking. The challenge we are faced with is to avoid overlooking a small nonfunctioning adrenal cortical car- cinoma, without performing too many adrenalectomies for benign inactive adrenal tumors because only a surgi- cal approach, which of course is connected with morbid- ity and mortality, can confirm the correct diagnosis of a benign adrenal lesion via the histopathologic examina- tion of the specimen. In view of the expected increase in the frequency of incidentally found adrenal lesions, we performed a retrospective analysis of the correlation be- tween preoperative diagnostic work-up and postopera- tive pathological diagnosis performed on 52 patients be- tween 1987 and 2001 in a single clinical center. The aim of the analysis was to define criteria for the establishment of a correct and cost-effective diagnosis, and the selection of patients suitable for surgery.
Patients and Methods
The clinical charts of 52 patients who underwent adrenalectomy between January 1, 1987 and December 31, 2001 for an inciden- tally found adrenal tumor at our institution were reviewed with respect to the reason for imaging procedures, the indication for surgical treatment, the surgical procedures, and the morbidity and mortality. The diagnosis was based on imaging methods which in- cluded abdominal ultrasound (US), abdominal CT scan and mag- netic resonance imaging (MRI). The diagnosis was confirmed post- operatively by means of a pathological examination. The largest diameter was the basis for the evaluation of the size. Hormonal investigations included the measurement of glucocorticoids, serum potassium, plasma aldosterone, plasma renin activity and plasma metanephrines.
Results
Of the 52 patients, 30 were female and 22 male with a median age of 56.4 years. At the time of surgery, 27% of the patients were younger than 50 years, whereas the ma- jority of the patients (65%) were between 51 and 70 years
| Age | n | % |
|---|---|---|
| <30 years | 1 | 2 |
| 31-40 years | 4 | 8 |
| 41-50 years | 9 | 17 |
| 51-60 years | 20 | 38 |
| 61-70 years | 14 | 27 |
| >70 years | 4 | 8 |
old (table 1). During the period between 1987 and 2001, 14% of the patients had been operated on in the first 5 years, 34% in the middle 5 years, and 55% of the patients had undergone surgery within the last 5 years.
In 30 patients, the incidentalomas were discovered during the diagnostic approach for different diseases. In 1 patient during imaging after an accident; in 11 patients during a routine sonography of the abdomen, and in 10 patients during abdominal imaging due to nonspecific ab- dominal pain. The reasons for taking a surgical approach were unclear significance of the adrenal lesion in 22 pa- tients, suspicion of malignancy in 5 patients, increase in size during regular follow-up in 8 patients, and maximum tumor diameter of more than 5 cm in 7 patients. The wish for surgical treatment due to fear of malignancy was the reason in 1 patient, and subclinical secretion of cortisol in 5 patients. In 4 patients, the reason for surgical resection was not sufficiently documented; however, size and growth seemed to be the major indications in these 4 cases.
The incidentalomas were situated on the left side in 15 patients and on the right in 37 patients. Twenty-eight patients underwent surgery using a conventional transab- dominal approach, 17 patients, a conventional dorsal ap- proach, and 7 patients via an endoscopic retroperitoneal approach. In 1 patient, the operation commenced with a dorsal approach for a hormonally inactive lesion of un- clear significance. Intraoperatively, the suspicion of adre- nocortical carcinoma arose, and the approach was con- verted to a transabdominal approach, with resection of the adrenal gland. The carcinoma having a maximum diameter of 7 cm was classifi ed as T2N0M0.
In 6 patients, additional resections of various other organs or tissues were performed such as hemihepatec- tomy next to cholecystectomy, cholecystectomy, hemico- lectomy next to cholecystectomy, appendectomy next to cholecystectomy, splenectomy and hemipancreatectomy in 1 patient each. The unplanned splenectomy was car-
| Adenoma | Myelolipoma | Unilateral nod. hyperplasia | Cystic lesions | Carcinoma | Total | |
|---|---|---|---|---|---|---|
| 0.1-1 cm | ||||||
| 1.1-2 cm | 3 (6%) | 3 (6%) | ||||
| 2.1-3 cm | 7 (13%) | 2 (4%) | 9 (17%) | |||
| 3.1-4 cm | 7 (13%) | 7 (13%) | ||||
| 4.1-5 cm | 6 (12%) | 2 (4%) | 2 (4%) | 1 (2%) | 11 (21%) | |
| 5.1-6 cm | 4 (8%) | 3 (6%) | 1 (2%) | 8 (15%) | ||
| >6 cm | 5 (10%) | 7 (13%) | 1 (2%) | 1 (2%) | 14 (27%) | |
| Total | 32 (62%) | 12 (23%) | 4 (8%) | 3 (6%) | 1 (2%) | 52 (100%) |
ried out because bleeding occurred intraoperatively. In another patient, an unplanned hemipancreatectomy was carried out because of intraoperatively discovered gluca- gonoma. In the other 4 patients, the adrenalectomy was performed during a planned operation for various other reasons. All these patients underwent surgery using the transabdominal approach and revealed a benign adeno- ma during the postoperative histopathologic examina- tion. One patient revealed a postoperative subcapsular hepatic hematoma requiring substitution of erythrocyte concentrates.
Histopathologic examination ruled out adrenal adeno- ma in 32 patients, adrenal myelolipoma in 12 patients, unilateral nodular hyperplasia in 4 patients, cystic lesion of the adrenal gland in 3 patients and an adrenocortical carcinoma in 1 patient. The mean size of all lesions was 5.5 cm (table 2). Twenty-five of 52 patients (48%) were younger than 60 years at the time of surgery and had an adrenal lesion exceeding 4 cm in size, including the pa- tient with the adrenocortical carcinoma.
Thirty-two patients could be followed up after a mean period of 4.3 years, but 7 patients had died 5.3 years after the adrenalectomy, i.e. data regarding post- operative outcome were available for 39 of 52 patients. In 6 of the 7 patients, death was related to nonadrenal causes. The patient with the incidentally discovered ad- renocortical carcinoma died due to local recurrence and a progressive systemic disease with pulmonary and he- patic metastases 3.7 years after the adrenalectomy. In 3 patients, a contralateral adrenal tumor was detected dur- ing further follow-up. Two of these patients had under- gone surgery before for unilateral adenoma, and one for unilateral myelolipoma. In 1 of the patients with a uni- lateral adenoma, surgical enucleation of the contralat-
eral tumor was carried out, sparing the adrenal tissue, and a histopathologic examination again revealed an ad- renal adenoma. Tests of the function of the remaining adrenal tissue revealed adequate secretory capacity. In the other patient who had been operated on before for unilateral adenoma, a contralateral adenoma was sus- pected, and in the patient who had undergone earlier surgery for unilateral myelolipoma, a newly developed contralateral myelolipoma was found. Both patients were followed up closely with regular abdominal imag- ing.
Discussion
In the last decade, incidentally found tumors have be- come an overall problem for the physician. This is also reflected in our series where more than half of the cohort underwent surgery within the last 5 years of the period mentioned above, although with the increasing improve- ments in diagnostics, the indication for surgery was ap- plied more stringently rather than more broadly. The in- cidence of incidentalomas correlates with the age of the patients. They occur mostly in people older than 50 years, as was confirmed by our data [2, 6, 7, 9-12]. This may be due to the increasing frequency in the use of imaging methods in older patients and the slow development of incidentalomas. Regarding abdominal US as the method of choice for abdominal imaging, incidentalomas have to reach a considerable size before they can be discovered with US. The predominance of the right side in our series can also be explained by the better visualization of the right adrenal gland with abdominal US [13]. With the frequent use of abdominal CTs more small incidentalo-
mas may be seen in the future, without the predominance of one particular side.
One possible reason for the development of inciden- talomas is a compensatory growth of adrenal nodules due to ischemic disease caused by hypertension or diabetes mellitus frequently found in older people [12, 14]. This theory correlates with the higher number of patients with hypertension, obesity and diabetes mellitus amongst those with an incidentaloma compared to the overall pop- ulation. However, it cannot be ruled out that patients with cardiovascular risk factors are more often exposed to imaging methods [15-19]. We could show that inci- dentalomas do not only occur in older people; 27% of the patients in our series presented with an age of less than 50 years and 65% with an age of less than 60 years at the time of the operation. With the increasingly widespread use of highly sensitive imagery with improved image res- olution, not only will the incidence of incidentalomas in- crease, but they will also be seen more often in younger patients.
The NIH state-of-the-science statement providing health care providers, patients and the general public with a responsible assessment of currently available data re- garding the management of clinically inapparent adrenal masses suggests that patients with tumors greater than 6 cm are usually treated surgically, while those with tu- mors smaller than 4 cm are generally monitored. In pa- tients with tumors between 4 and 6 cm, criteria in addi- tion to size should be considered in making the decision to monitor or proceed to adrenalectomy. [20]. However, 19 of 52 patients (37%) in our study had had an inciden- taloma with a tumor diameter ranging from 4 to 6 cm.
Size is regarded as one of the major risk factors for malignancy [1, 4, 14, 21]. The majority of adrenocortical carcinomas presumably have a size of over 6 cm because they have been discovered at a late stage and grow rela- tively quickly. Also, fast growth over time is a clinical characteristic of malignancy. Proof of the opposite, name- ly that adrenal tumors of less than 4 cm are not suspected of being malignant, is yet to be produced. If one waits with surgery until the size of adrenal tumors exceeds 6 cm, then of course all discovered adrenocortical carci- nomas will in the future indeed remain over 6 cm in size, which is the classic phenomenon of a self-fulfilling proph- ecy. The overwhelming majority of incidentalomas are nonfunctional adrenal adenomas with a frequency of up to 80% [3, 5-7], but nearly 40 different diagnoses have been associated with adrenal incidentalomas [3, 22]. Ret- rospectively, a small number of adenomas and a large number of adrenal cortical carcinomas should be expect-
ed to be found in surgical series for an optimal relation. However, the number of adrenal adenomas in relation to all incidentalomas strongly depends upon the indications for surgical resection in the different studies.
The size of an incidentaloma determined by imaging should be assessed with care because this, and therefore also a change in size, was often underestimated [23-25]. An image-guided fine-needle biopsy is not an adequate diagnostic method for the differentiation between an ad- renal adenoma and an adrenal carcinoma, but only for the differentiation between adrenal tissue and metastatic tissue [4-7, 26]. In all adrenal lesions, a tendency towards incremental growth or very slow growth must be assumed because they grow at different rates and will have at some time reached their present size. However, in addition to the determination of the maximum size, the detection of a clinically significant change in size and the validation of the reproducibility of the measurements also have to be defined. Regarding the indication for surgical treat- ment, the NIH state-of-the-science statement gives some cut-off values for the size of the lesion. In contrast, the indication for surgical removal of the incidentaloma in relation to the extent of growth is unclear. Since the rea- son for the development and the growth behavior remain unclear, it can be postulated that every incidentaloma can grow up to a diameter of 4 or 6 cm in a reasonable amount of time if one waits long enough in young patients. Only surgically treated patients were included in our series; we have not considered the clinical course of patients with adrenal incidentalomas that have been monitored. With the benefit of hindsight, the surgical treatment in 51 of our 52 patients was unnecessary, but preoperatively there had been other reasons such as unclear significance, sus- picion of malignancy, increase in size detected during regular follow-up and - what seems to be one of the most important reasons - the patient’s wish for surgical treat- ment due to fear of malignancy. Younger patients in par- ticular must either be under life-long control or have the adrenal lesion resected. A repeated and life-long close fol- low-up in the case of an anxious patient who is informed of the diagnosis will sometimes exceed the cost of a single operation. In addition to size, the individual patient’s fear of malignancy and the age of the patient should be crite- ria to be considered in making the decision to monitor or proceed to adrenalectomy. Therefore, we suggest that es- pecially in patients younger than 60 years of age adrenal lesions exceeding 4 cm in size should be resected. We were able to demonstrate that 48% of the patients in our study fulfilled these criteria.
The tendency towards a surgical approach is further encouraged by the introduction of endoscopic resection, in terms of postoperative recovery, pain, anxiety, length of hospital stay, morbidity, mortality and overall costs [27-31]. With this approach, the patient with an adrenal incidentaloma can be safely treated and the suspicion of a benign adrenal tumor can be confirmed. The indication of surgical therapy should also be based on the ability of the treating institution to offer an endoscopic approach. This approach should be performed in specialized centers with high patient volumes. Tumors up to 8 cm can be operated on using the endoscopic approach. The endo- scopic removal of larger tumors is possible of course, and the effectiveness and safety have been demonstrated by some authors [32, 33]. If the malignancy is confined to the adrenal gland, endoscopic resection may be feasible if the principles of oncological surgery are respected, but long-term follow-up is needed to establish this approach [34, 35]. However, most adrenal cortical carcinomas in- filtrate surrounding tissues, and resection of flanking tis- sues and organs is necessary and is most suitably per- formed using an open transabdominal approach [36-38]. Additionally, the risk of encountering an incidental adre- nal carcinoma is distinctly increased [32], and patients treated endoscopically have a high risk of developing peritoneal carcinomatosis [39]. Therefore, open adrenal- ectomy still remains the standard surgical procedure to
achieve proper resection margins and to treat infiltrated tissue and organs. The largest tumor in our series on which this approach was used was an adrenal adenoma with a size of 5.5 cm. In the case of malignancy, the op- eration can be converted to an open, conventional trans- abdominal approach. An adrenalectomy for incidentalo- ma can also be carried out using a transabdominal ap- proach during the resection of other tissues or organs, as shown in our series. But the indications for endoscopic adrenalectomy should not be altered because of the avail- ability of a gentle surgical approach [7]. Intra- or postop- erative complications from unnecessary surgery should always be avoided.
In conclusion, apart from the imaging and endocrine evaluation, the clinician should also consider individual patient characteristics, clinical condition such as comor- bid syndromes and personal knowledge of the individual patient [40]. The psychological effect on a patient in- formed of the diagnosis is an important aspect of making recommendations for treatment. Additionally, a regular and life-long close radiological and endocrine follow-up in the case of an anxious patient with knowledge of the diagnosis may quite often exceed the cost of a single en- doscopic surgery. Treatment should be tailored to the in- dividual patient. Especially in the case of patients youn- ger than 60 years with adrenal lesions exceeding 4 cm in size, an adrenalectomy should be performed.
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