B79;15sep99

Asymptomatic Adrenal Tumours: Criteria for EndoscopicRemoval L. A. Michel,1 L. de Cannie`re,1 E. Hamoir,2 G. Hubens,4 M. Meurisse2 and J. P. Squifflet3 From the 1Mont-Godinne University Hospital (UCL), Yvoir, 2CHU du Sart Tilman (ULg), Lie`ge, 3St. Luc Academic Hospital (UCL),Brussels, 4Universitair Ziekenhuis Antwerpen, Antwerp, Belgium ABSTRACTObjective: Assessment of criteria for videoscopic removal of adrenal lesions discovered incidentally.
Design: Open prospective study.
Subjects: 63 patients operated on for 65 adrenal tumours.
Outcome Measures: Relevance of proposed criteria: secreting adrenal lesion; diameter larger than 4 cm or increase in size atany re-evaluation; computed tomogram of intratumoral necrosis, haemorrhage, or irregular margins; high concentrations ofdehydroepiandrosterone (DHEAS).
Results: Laparoscopic adrenalectomy was successful in 61 patients (97%). There were 4 minor complications. Criteria allowedus to identify correctly : phaeochromocytoma (n = 23), primary hyperaldosteronism (n = 18), Cushing’s adenoma or disease(n = 7), single metastasis (n = 4), adenoma with DHEAS or cortisol hypersecretion (n = 3). 8 non-secreting incidental tumours(13%) were operated on.
Conclusion: Simple criteria for videoscopic adrenalectomy for lesions discovered incidentally allowed us to reduce the numberof doubtful indications (positive predictive value 87%).
Key words: laparoscopy, retroperitoneum, adrenalectomy, phaeochromocytoma, hyperaldosteronism.
feasibility and safety of endoscopic adrenalectomy (1),we refused to lower the threshold for removing Asymptomatic and apparently “non-functioning” adre- incidentally-found adrenal tumours. The simple criteria nal tumours may be discovered during the course of adopted for open adrenal surgery (8) should also be investigations for unrelated conditions. For instance, unsuspected adrenal masses are detected in 2% of The current study aims to assess these criteria for abdominal computed tomograms (CT) (4). We still do videoscopic adrenalectomy for lesions discovered not know whether such tumours are indeed silent or incidentally: secreting adrenal lesion; diameter larger whether they produce inactive precursor hormones or than 4 cm or increase in size at any re-evaluation; CT active hormones in insufficient amounts to produce of intratumoral necrosis, haemorrhage, or irregular signs or symptoms, nor do we know their natural margins; or high concentrations of dehydroepiandro- history or whether with time they will start to sterone sulphate (DHEAS). We report our experience “function”. However, the quest for diagnostic certainty with such criteria in a prospective multicentre study, must be tempered by the need to avoid iatrogenic conducted by the Belgian Group for Endoscopic complications, so we may question the somewhat irrational management strategy that some surgeonselect for such tumours: to operate on all of them despitethe fact that a policy of exploring all incidental adrenal Open adrenalectomy is not a common operation and the newly developed laparoscopic approach is even A check list was sent to those members of the BGES more rarely used by surgeons dealing with endocrine who were already experienced in laparoscopic surgical disorders. However, the advantages of the endoscopic techniques and open adrenalectomy for endocrine approach has led some surgeons to widen their disorders, and who were planning to use the new indications for adrenalectomy to a doubtful degree so endoscopic approach to collect data prospectively as to increase their operative series unjustifiably.
about videoendoscopic adrenalectomy. The report Despite our reported preliminary results about the form (1) includes information about the patient’s age, 1999 Scandinavian University Press. ISSN 1102–4151 Table I. Indications for endoscopic adrenalectomy or Cushing’s syndromes, carcinoma, or metastasis).
False positives are those tumours that met one of four criteria, but that after operation were found to bebenign, non-secreting tumours. True negatives are those tumours that met none of the four criteria, that were not operated on, and follow-up of which showed that they had been correctly identified as incidental findings. Theoretically, false negatives are those tumours that met none of the criteria, but were shown after operation to have been secreting or cancerous lesions, or both, that had to be operated on. However, according to our protocol, patients whose tumours met none of the criteria were not operated on but carefully followed up. This means that there were no falsenegative tumours (n = 0), which introduces an investi-gation bias. In the current series, therefore, the only rate sex, clinical features (preoperative risk factors, Amer- that can be pertinently proposed for the evaluation of ican Society of Anesthesiology (ASA) clinical status criteria studied is the positive predictive value, which is classification, previous abdominal surgery, preopera- not influenced by either the false negative or true tive diagnosis of adrenal disease, blood pressure, preoperative imaging techniques, coexisting condi-tions, and preoperative pharmacological preparation).
Data were also obtained about the proposed surgicaltechnique Sixty three patients had a videoendoscopic adrenalect- both), duration of operation, transfusion requirement, omy, 42 women and 21 men with a median age of 41 morbidity, anaesthetic considerations, pathological (range 12–74). Of the 65 adrenalectomies, 36 were on results, hospital stay, and follow-up. It is important to the left, 25 on the right, and two were bilateral (Table mention that this study includes all adrenalectomies I). Thirty one patients (49%) had had a previous done in the parent institutions by four surgical teams abdominal operation, and six patients with multiple once they started with this new surgical approach: the endocrine neoplasia syndrome (five phaeochromo- first endoscopic adrenalectomy was done in October cytomas and one Cushing’s disease) had previously 1993, another team started in 1994, and two in 1995.
had the other adrenal operated on. Seventeen patients The two first cases done in 1993 and in early 1994 were (27%) had a body mass index [weight (kg) Ä height not incidental adrenal tumours, but starting with the (m2)] of over 30, which means that they were regarded third case our protocol included proposed criteria for as clinically obese (5). The 63 patients had a total of 102 coexisting clinical risk factors. Preoperative riskaccording to the ASA classification were grade I (n = 17), grade II (n = 35) and grade III (n = 11). All Data were acquired from four university surgical 63 patients had a preoperative CT scan. Patients teams. All cases were operated on between October suspect of having phaeochromocytoma also had 1993 and September 1997. The database was managed meta-iodobenzylguanidine (MIBG) scintigrams.
by project coordinators designated by the board of the The initial endoscopic approach to the adrenal was transperitoneal in 60 patients (59 supracolonic and onetransmesocolic to gain access to the left adrenal), and retroperitoneal in three. Sixty patients were operated on The sensitivity, specificity, and predictive values for in the lateral decubitus position and three in the adhering or not adhering to the proposed criteria were semilateral position. The median diameter of the calculated by standard methods. For the purpose of tumours was 4 cm (range 1.5–12). The median duration computing these values, true positive, true negative, of the procedure was 120 minutes (range 60–360), and false positive and false negative results were calculated the median postoperative stay was 4 days (range 2–13).
(patients whose tumours met at least one of the four Endoscopic adrenalectomy was successful in 61 criteria compared with those that met none of the four patients (97%). The two unsuccessful procedures were criteria). True positives are defined as those tumours bilateral, one for Cushing’s disease and one for ACTH- that met one to four criteria and that were operated on secreting metastases from a malignant thymoma.
for a definite indication (phaeochromocytoma, Conn’s Conversion was justified by bleeding in the first case and difficult endoscopic dissection in the second case.
CT at six-monthly intervals for the first year and then Postoperative complications for the overall series were yearly thereafter; and by an annual 24-hour urine two pleural effusions and one basilar artery thrombosis screen for VMA, metanephrine, catecholamine, 17- two weeks postoperatively. One patient operated on for hydroxycorticosteroid, and 17-ketosteroid concentra- a left pheochromocytoma and a 12-cm diameter cyst of tions. The serum potassium concentration is also the upper pole of the left kidney had to be reoperated on measured each year. So far, none of these four patients 12 hours later for bleeding in the retroperitoneal space.
(true negatives) have met the proposed criteria for Oozing was found and controlled laparoscopically.
operation and are, therefore, not included in the This patient was the only one who required a blood transfusion. The median duration of follow-up was 9 If one considers the overall series of 63 who were months (range 2–48). Only one patient (operated on for operated on (true positives and false positives) and the a unilateral pheochromocytoma) had an abnormal four who were not operated on (true negatives), catecholamine concentration, which was caused by adherence to the criteria allowed us to estimate the adrenal hyperplasia on the other side.
positive predictive value of the criteria and correctly During the study period, 20 patients had had identify definite indications for adrenalectomy (posi- abdominal CT for unrelated clinical problems that tive predictive value 87%; 95%-confidence interval showed unexpected adrenal tumours. Sixteen of those who fulfilled the criteria were operated on and areincluded in the series of 63 endoscopic adrenalec- tomies. There was no significant difference in age, sex,tumour size, or risk factors between the patients with When a modern organ-imaging technique is used to non-incidentally and incidentally discovered adrenal follow-up patients with known malignant disease and tumours. Autonomous production of cortisol by these shows a mass in the adrenals, one is not dealing with an apparently non-functioning adrenal masses was sought incidental finding. This is also true when an adrenal by a 48-hour dexamethasone suppression test (2 mg), mass is discovered by CT or ultrasound scan ordered or recognised by lack of a normal circadian rhythm for because of the clinical suspicion of abnormal adrenal cortisol and chronically suppressed ACTH (a high function. Management of the incidentally found cortisol Ä ACTH ratio). Aldosterone, DHEAS, andro- tumour must be guided by the high incidence of benign gen, and oestrogen concentrations were also measured.
and clinically unimportant adrenal adenomas com- To exclude autonomous adrenal medullary function, pared with the rarity of occult non-functioning adre- 24-hour urinary noradrenaline, adrenaline, vanillyl- nocortical carcinoma or functioning adenoma (4). The mandelic acid (VMA), metanephrine, and normeta- feasibility of laparoscopic adrenalectomy has led some nephrine concentrations were also measured. A cloni- investigators (2, 3) to suggest that this new approach dine suppression test was done for four patients, whose should lower the threshold for removing adrenal urinary catecholamine concentrations were raised, and tumours found incidentally. However, the value of was normal. After these investigations we were reason- removing such tumours, whether endoscopically or by ably certain that eight of the tumours were secreting: the open technique, remains controversial (6, 7, 10, three phaeochromocytomas, one cortisol hypersecre- tion (pre-Cushing’s syndrome), and four hyperaldo- Despite our previously reported experience about the feasibility, the better postoperative comfort, and the Eight other patients with non-secreting incidental safety of endoscopic adrenalectomy (1), we refused to tumours were also operated on (false positives): one lower the threshold for removing incidental tumours.
31-year old man for a raised DHEAS and seven Even if criteria for operative and non-operative patients because the diameter of the tumour was treatment are still being debated, not all such tumours more than 4 cm or had increased in size on re- should be operated on. We therefore question the evaluation, and whose CT showed intratumoural somewhat irrational management strategy that some necrosis, haemorrhage, or irregular margins). One, minimally invasive surgeons adopt for such tumours: which measured 6 cm, was a schwannoma and the that is to operate on any incidentally discovered and other seven were non-functional benign adenomas.
non-functioning adrenal tumours that could just be left These eight patients make up 13% of the total series of in place. A recently updated series (2) concerns 50 new 63 who were operated on. In the meantime, four other cases in less than two years in Canada, the population tumours found incidentally met none of the criteria and of which is the same as that of the Benelux countries.
were not operated on. They were free of symptoms and This series of 50 new cases of videoscopic adrenalec- still not secreting respectively 42, 30, 24, and 18 tomies can certainly be explained by the superb months after diagnosis. They are followed up by serial technique of the surgeons, but we also question their 14% incidence of debatable adrenal lesions vaguely for unnecessary surgery. The potential major benefit of classified as other or data not available, in addition to early removal of a rare adrenal carcinoma must be the 15% of adrenal lesions classified as non-function- balanced against the morbidity and mortality of surgery ing adrenal tumours found incidentally, which makes for the far more common benign lesions. Similarly, the benefit of detection of malignancy by fine needle This is the reason why we have adopted the four biopsy must be balanced against the small but real risk simple criteria recommended in a recent large study (8) of procedural complications in those without the for removal of these tumours, that seem to fit reason- ably within the framework of current knowledge. As Observation alone also entails costs, both monetary this policy was recommended for open adrenal surgery, and psychologica1, particularly for young patients. The we have followed it for videoscopic surgery. Adhering specific willingness of the patient to have the tumour to these criteria allowed us to obtain a high incidence of removed deserves consideration, even if it is not a clear-cut endocrine indications for surgical removal of rational criterion and was discarded in our protocol.
tumours at high risk of endocrine disorders, or How the costs and benefits of various strategies of malignancy, or both (phaeochromocytoma, Conn’s hormonal screening, and radiological and invasive and Cushing’s syndromes, metastatic, or other secret- techniques for evaluation of incidental adrenal tumours ing lesions make up 87% of our series of endoscopic compare with other diagnostic problems (such as adrenalectomies). The remaining 13% that have treatment of hypertension or hypercholesterolaemia) debatable indications is low compared with those in await further study. The role of magnetic resonance other series (2, 3, 10). If surgeons are able to do a imaging (MRI) is still under discussion (9). It has been laparoscopic adrenalectomy safely, it might sometimes used to distinguish between benign adenomas and influence the therapeutic option in as much as the malignant adrenal tumours by comparing the intensity nature of the adrenal mass may be resolved less of the lesion signal to the signal intensity of liver, invasively and with less disability than by open striated muscle, or fat. Benign adenomas usually have a surgery. Nevertheless, there is always a risk that a low intensity ratio, whereas malignant masses and laparoscopic procedure will have to be converted to an phaeochromocytomas have a high signal intensity ratio open operation. Consequently, the availability of (9). Contrast enhancement after injecting gadolinium laparoscopic adrenalectomy should not change the diethylenetriaminepenta-acetic acid (Gd-DTPA) and indications for advising operation in a patient with an comparing intensity ratios before and after contrast enhancement has further aided the differential diag- For patient with hypertension and an apparently non- nosis (6). The range of criteria vary, however, when functioning adrenal mass, phaeochromocytoma should using different MRI techniques and equipment, so if a always be excluded, as well as normokalaemic primary strategy using MRI is promising it has still to be hyperaldosteronism, which is much more common than confirmed, and in the meantime we have to rely on previously suspected. Low DHEAS concentrations have been suggested as a marker for an adrenaladenoma secreting cortisol at a rate not sufficient to cause overt Cushing’s syndrome (pre-Cushing’s syn-drome). Several workers have found, however, that the We thank Doctor Jacques Jamart, department of sensitivity and specificity were only in the 50%–70% biostatistics, for critical review of the statistical range. Part of this problem may relate to the normal fall in DHEAS secretion with age, so that its use as ascreening test might be more accurate in younger patients. On the other hand, among clinically diag-nosed primary adrenal cancers, excessive adrenal 1. Decanniere L, Michel LA, Hamoir E, Hubens G, androgen secretion is the most common hormonal Meurisse M, Squifflet JP. Multicentric experience of abnormality, suggesting that increased DHEAS secre- the Belgian Group for Endoscopic Surgery (BGES) withendoscopic adrenalectomy. Surg Endosc 1997; 11: tion may be used as a screening test, particularly in young patients. However, there are few data on which 2. Gagner M. Laparoscopic adrenalectomy. Surg Clin Noth to base this among patients with incidentally-found 3. Gagner M, Lacroix A, Prinz RA, et al. Early experience Applying a screening test with less than 100% with laparoscopic approach for adrenalectomy. Surgery1993; 114: 1120–1124.
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Incidentalomas of the adrenal gland: 36 operated

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