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ENDOCRINE SURGERY
Fig. 31.2. This larger than 6-cm adrenal incidentaloma was suspicious for malignancy on CT scan (a) but histologically was proved
a benign cortical tumor (b). (Reprinted with permission from Linos DA, Adrenal glands: diagnostic aspects and surgical therapy.
Heidelberg: Springer-Verlag; 2005. 246).
adrenal tumors that did (Figs. 31.2 and 31.3). In
several series, adrenocortical carcinomas with a
maximum diameter of 3 cm or less have been
described [15, 34, 38, 48].
The size of an adrenal incidentaloma as
reported on a CT scan is usually less than the
size reported on the histology report. This
underestimation ranges from 16% to 47% [49].
In an analysis of the CT and histology reports of
76 patients with various diseases, we found that
the mean estimated diameter of the adrenal
tumor was 4.64 cm on the CT report when the
real size (pathology report) was 5.96 cm.
Further analysis of different CT scans revealed
a consistent underestimation in all groups. In
the group of adrenal tumors with a maximum
diameter of less than 3 cm, the mean diameter
reported on CT was 2.32 cm in contrast to the
true histological size of 3.63 cm (p < 0.001). We
therefore proposed the formula Histologic
Size ¼ 0.85 + (1.09 CT size) to correct the
underestimated CT size so as to use the size
criterion more accurately [49]. A study from
Mexico [50] showed that the above ‘‘Linos formula’’ turned out to be significantly more accurate than the direct radiologic measurements in
predicting thereal pathological size of the tumor.
with areas of necrosis; such lesions are suggestive of malignancy, especially if enlarged lymph
nodes or local invasion is also detected.
On MR imaging studies, one should look for
heterogeneously increased, early T2-weighted
signal, weak and late enhancement after gadolinium injection or an intravascular signal identical to the tumor signal. When NP59 scintigraphy
is available, the lack of (or very weak) uptake in
the tumor and normal contralateral uptake is
suspicious for malignancy. Positron emission
tomography (PET) can be used following the
administration of 2-deoxy-2[
The 18F-FDG-PET scan is a useful tool confirming
isolated metastases and in selecting patients for
adrenalectomy. It has been used in studies to distinguish between primary and metastatic adrenal
lesions, especially in patients with other primary
malignancies [51] (Fig. 31.4). In patients with
oncologic history the combination of MRI and
18F-FDG-PET scan provided accurate differentiation between metastases and benign adenomas as
illustrated in one study of 42 patients with adrenal
incidentalomas [52].
18F
] fluoro-D-glucose.
Fine-Needle Aspiration
Imaging
In addition to assessing distant metastasis and
tumor size, imaging studies may suggest malignancy. On CT, one may see a poorly delineated
ragged tumor with stippled calcifications and
Fine-needle aspiration (FNA) biopsy of an adrenal
incidentaloma has a limited role. It is useful in
cases of coexistent extra-adrenal malignancy
(usually lung cancer) to confirm the radiologic
evidence of adrenal metastasis. Generally, FNA
cannot differentiate cortical adenoma from carcinoma because it cannot detect invasion of the
421
INCIDENTALOMA
Fig. 31.3. The size of the adrenal incidentaloma does not necessarily predict the clinical severity of the problem. (a) A 9-cm
maximum diameter benign schwanoma. (b) A 7-cm maximum diameter benign hemorrhagic cortical adenoma. (c) A 2.9-cm
potentially lethal pheochromocytoma. (Reprinted with permission from Linos DA, Adrenal glands: diagnostic aspects and surgical
therapy. Heidelberg: Springer-Verlag; 2005. 247).
tumor into the capsule. In a study by Silverman
and coworkers [53], 3 of 33 FNA specimens that
contained ‘‘benign’’ adrenal tissue were later
proved to be malignant. Each malignant lesion
wassmallerthan3cmindiameter.In14patients
in whom the FNA was nondiagnostic, two masses
proved to be malignant. Although it has been suggested that FNA is useful in the differential diagnosis of a cystic adrenal mass, such practice is not
recommended because cystic pheochromocytomas are prevalent. Diagnostic puncture of such a
lesion (or of a rare cystic echinococcal parasitic
cyst) can be harmful to the patient. The possibility
of seeding a malignant adrenal neoplasm in the
retroperitoneum is an additional reason that FNA
should be discouraged.
Genetic and Molecular
Biology Studies
Currently, the only accepted confirmatory criteria to determine whether an adrenal incidentaloma is benign or malignant are the presence
422
ENDOCRINE SURGERY
ab
cd
Fig. 31.4. A 43-year-old wf (white female) with a history of bilateral mastectomies for extensive in situ lobular breast carcinoma 18
months ago. Currently a right adrenal incidentaloma is discovered. (a) CT of a 5-cm right adrenal mass (30 units of Hounsfield). (b)MRI
appearance of the same lesion. (c) 18F-FDG-PET scan with increased metabolic function (SUV max 4) in the right adrenal indicating
metastatic lesion. (d) The gross specimen (6.7 6.4 cm in diameter) that eventually proved to be a benign ganglioneuroma.
of metastasis (synchronous or metachronous)
and/or local invasion into adjacent structures.
The mapping and identification of genes responsible for hereditary syndromes (e.g., multiple
endocrine neoplasia type 1, Li-Fraumeni) have
increased our understanding of adrenocortical
tumorigenesis. Oncogenes andtumor-suppressor
genes involved in adrenal carcinomas include
mutations in the p53 tumor-suppressor gene.
Amongst those, the Ki67 index (% immunopositive cells) when above 5% can be a useful
indicator in the differentiation of adenomas
from carcinomas [54]. Adrenal carcinomas are
monoclonal, whereas adrenal adenomas may be
polyclonal in approximately 25–40% of cases
[55, 56]. Although these findings do not have
direct clinical application, it is hoped that future
research will facilitate the diagnosis and predict
the natural course of these tumors.
Management of Adrenal
Incidentalomas: Surgery
Versus Follow-Up
The management of adrenal incidentalomas
remains controversial despite the commissioned systematic review of the literature at the
state of the science conference sponsored by the
National Institute of Health [58, 59].
423
INCIDENTALOMA
Several recent studies demonstrated that:
1. A relatively high percentage of adrenal incidentalomas, especially adrenal cortical adenomas, are subclinically functioning.
2. A relatively high percentage of patients with
adrenal incidentalomas display pathological
features, such as impaired glucose tolerance,
insulin resistance, increased blood pressure,
high triglyceride levels, low HDL, central fat
deposition, and reduced trabecular bone
mineral density.
3. When adrenalectomy was done in patients
who either had proven subclinical hypercortisolism or had even truly nonfunctioning
tumors, the associated abnormalities and
symptoms (such as hypertension, obesity,
and altered glucose tolerance) were normalized or significantly improved.
In the era of laparoscopic adrenalectomy that
carries a minimal morbidity and mortality, it
appears logical to advocate surgery in patients
with adrenal incidentalomas when
1. There is laboratory evidence for a subclinically functioning tumor
2. There are associated pathological features
such as hypertension, impaired glucose tolerance (or diabetes), pathological triglyceride profile, central fat deposition, reduced
bone mineral density
3. There is clinical and radiological evidence
of primary or solitary metastatic adrenal
carcinoma.
The age and the anxiety of the patient should
also play a role in the decision to operate or not.
Conservative management is recommended of
those patients with adrenal incidentalomas in
whom: (1) There is no clinical or laboratory
evidence for subclinical function of the tumor,
(2) there are no associated symptoms potentially related to the adrenal incidentaloma, and
(3) there is no suspicion of adrenal carcinoma.
In these patients a yearly checkup should be
continued for 5–10 years with the main emphasis on the possibility that the silent, nonfunctioning tumor may subsequently develop
hyperfunction.
Complete though limited follow-up studies
(with repeated radiologic and hormonal evaluation) have been performed on patients with
adrenal incidentalomas. A multicenter Swedish
prospective study including 229 patients with
incidentaloma published controversial results
after a median follow-up of only 2 years. They
reported an increase in size in 7.4% and hypersecretion in 2% during this time. No cancer was
detected although only 79% of the patients not
primarily adrenalectomized were followed with
CT [57]. Barzon and associates [60] followed 75
patients with adrenal incidentalomas, observed
them for a median of 4 years, and found nine
adrenal incidentalomas to have enlargement.
Overt Cushing’s syndrome developed in two
patients, subclinical Cushing’s syndrome in
three, and clinical pheochromocytoma in one.
No patient had a malignancy. The estimated
cumulative risks for mass enlargement and
hyperfunction were 18 and 9.5%, respectively,
after 5 years, and 22.8 and 9.5% after 10 years. In
another study [61], 53 patients with adrenal
incidentalomas were followed for 6–78 months
(medium 24 months). During the follow-up, 22
lesions (41.5%) increased in size and 6 lesions
(11.3%) decreased in size or disappeared. No
adrenal incidentaloma grew or developed
hypersecretion. Thus, during follow-up of the
truly nonfunctioning adrenal incidentaloma,
yearly hormonal evaluation rather than repeating imaging studies for size monitoring should
be emphasized.
What is the Best Surgical
Approach in the Management
of Adrenal Incidentalomas?
Traditionally, surgical approaches to the adrenals have been anterior transperitoneal, posterior extraperitoneal, and thoracoabdominal (for
large tumors) [62]. The application of laparoscopic techniques in surgery of the adrenal
glands has essentially replaced all traditional
open approaches in the same manner that
laparoscopic cholecystectomy has replaced traditional open cholecystectomy. Because there
are so many benefits associated with the laparoscopic approach, open adrenalectomy should be
reserved for the large/potentially malignant
tumors or documented adrenocortical carcinomas invading the surrounding tissues. We have
compared the anterior, posterior, and laparoscopic approach in 165 patients who underwent
adrenalectomy between 1984 and 1994 [63].
Although in this study we included our early
424
ENDOCRINE SURGERY
cases and learning experience, the advantages of
the laparoscopic approach were clearly shown in
terms of morbidity (12.2% in the anterior
approach, 8.1% in the posterior approach, and
0% in the laparoscopic approach), mean operating time, mean length of postoperative hospitalization (8.1 days vs 4.5 days vs 2.7 days), and
minimal postoperative pain. The lack of long incisions and their immediate and long-term complications (e.g., wound infection, hernia, esthetic
dissatisfaction) and the opportunity for an early
return to full activity make the laparoscopic
approach the procedure of choice for nearly all
adrenal incidentalomas, including the laparoscopically removable primary or secondary carcinomas [31, 64] (Fig. 31.3). The anterior (or lateral)
laparoscopic adrenalectomy enables the removal
of large tumors, the performance of additional
procedures (e.g., cholecystectomy), and the performance of bilateral laparoscopic adrenalectomies when indicated [65, 66]. The laparoscopic
approach is used in almost all adrenal masses
independent of the size with the exception of
the adrenal carcinoma infiltrating the surrounding tissues as seen on preoperative imaging
studies. There is always the possibility to convert
the laparoscopic approach to a hand-assisted
laparoscopic adrenalectomy [7] or an open adrenalectomy if needed (see Chapter 33). Recently
the posterior retroperitoneal adrenalectomy that
was introduced and standardized by M. Waltz
[67] offers additional advantages such as avoidance of intraabdominal adhesions, no need for
mobilization of intraperitoneal organs and
easier direct access to the adrenal especially
is obese patients. It appears to be a faster
procedure especially in the case of bilateral adrenalectomy [68].
References
1. Copeland PM. The incidentally discovered adrenal
mass. Ann Surg. 1984;199:116–122.
2. Linos D. Adrenaloma: a better term than incidentaloma.
Surgery. 1989;105:456.
3. Grumbach M, Biller B, Braunstein G, et al. Management
of the clinically inapparent adrenal mass (‘‘incidentaloma’’). Ann Intern Med. 2003;138(5):424–29.
4. Young AE, Smellie WD.The adrenalglands inendocrine
surgery, 2nd ed. In: Farndon JR, editor. London: WB
Saunders; 2001. 123–4.
5. Ross NS, Aron DC. Hormonal evaluation of the patient
with an incidentally discovered adrenal mass. N Engl J
Med. 1990;323:1401.
6. Mantero F, Terzolo M, Arnaldi G, Osella G, Masini AM,
et al. A survey on adrenal incidentaloma in Italy. J Clin
Endocrinol Metab. 2000;85(2):637–44.
7. Shen WT, Sturgeon C, Duh QY. From incidentaloma to
adrenocortical carcinoma: the surgical management of
adrenal tumors. J Surg Oncol. 2005;89(3):186–92.
8. TerzoloM,BossoniS,AliA,DogaM, Reimondo G, Milani
G, Peretti P, Manelli F, Angeli A, Guistina A. Growth
hormone (GH) responses to GH-releasing hormone
alone or combined with arginine in patients with adrenal
incidentaloma: evidence for enhanced somatostatinergic
tone. J Clin Endocrinol Metab. 2000;85(3):1310–5.
9. Terzolo M, Pia A, Ali A, Osella G, et al. Adrenal incidentaloma: a new cause of the metabolic syndrome. J Clin
Endocrinol Metab. 2002;87(3):998–1003.
10. Rossi R, Tauchmanova L, Luciano A, Di Martino M,
Battista C, Del Viscovo L, Nuzzo V, Lombardi G. Subclinical Cushing’s syndrome in patients with adrenal
incidentaloma: clinical and biochemical features. J Clin
Endocrinol Metab. 2000;85(4):1440–8.
11. Midorikawa S, Sanada H, Hashimoto S, Suzuki T, Watanabe T. The improvement of insulin resistance in
patients with adrenal incidentaloma by surgical resection. Clinical Endocrinology. 2001;54(6):797–804.
12. Fernadez-Real JM, Engel WR, Simon R, et al. Study of
glucose tolerance in consecutive patients harbouring
incidental adrenal tumours: Study Group of Incidental
Adrenal Adenoma. Clin Endocrinol (Oxf). 1998;49:53.
13. Garrapa GGM, Pantanetti P, Arnaldi G, Mantero F,
Faloia E. Body composition and metabolic features in
women with adrenal incidentaloma or Cushing’s syndrome. J Clin Endocrinol Metab. 2001;86(11):5301–6.
14. Chiodini I, Torlontano M, Carnevale V, Guglielmi G,
Cammisa M, Trischitta V, Scillitani A. Bone loss rate in
adrenal incidentalomas: a longtitudinal study. J Clin
Endocrinol Metab. 2001;86(11):5337–41.
15. Young WF. Management approaches to adrenal incidentalomas. A view from Rochester, Minnesota. Endocrinol Metab Clin North Am. 2000;29(1):159–85.
16. Abecassis M, McLoughlin MJ, Langer B, et al. Serendipitous adrenal masses: Prevalence, significance and
management. Am J Surg. 1985;149:783.
17. Herrera MF, Grant CS, van Heerden JA, et al. Incidentally discovered adrenal tumors: an institutional perspective. Surgery. 1991;110:1014.
18. Caplan RH, Srutt PJ, Wickus G. Subclinical hormone
secretion by incidentally discovered adrenal masses.
Arch Surg. 1994;129:291
19. Bovio S, Cataldi A, Reimondo G, Sperone P, Novello S,
Berruti A, Borasio P, Fava C, Dogliotti L, Scagliotti GV,
Angeli A, Terzolo M. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest. 2006;29(4):298–302.
20. Guerrieri M, De Sanctis A, Crosta F, Arnaldi G, Boscaro
M, Lezoche G, Campagnacci R. Adrenal incidentaloma:
surgical update. J Endocrinol Invest. 2007;30(3):200–4.
21. Belldegrun A, Hussain S, Seltzer SE, et al. Incidentally
discovered mass of the adrenal gland. Surg Gynecol
Obstet. 1986;163:203.
22. Mantero F, Masini AM, Opocher G, et al. Adrenal incidentaloma: an overview of hormonal data from the
National Italian Study Group. Horm Res. 1997;47:284.
23. Linos DA, Stylopoulos N, Raptis SA.Adrenaloma: a callfor
more aggressive management. World J Surg. 1996;20:788.
425
INCIDENTALOMA
24. Bitter DA, Ross DS. Incidentally discovered adrenal
masses. Am J Surg. 1989;158:159.
25. Caplan RH, Kisken WA, Huiras CM. Incidentally discovered adrenal masses. Minn Med. 1991;74:23.
26. Cajraj H, Young AE. Adrenal incidentaloma. Br J Surg.
1993;80:422.
27. Geelhoed GW, Druy EM. Management of the adrenal
‘‘incidentaloma’’. Surgery. 1992;92:866.
28. Didolkar MS, Bescher RA, Elias EG, etal. Naturalhistory
of adrenal cortical carcinoma: a clinicopathologic study
of 42 patients. Cancer. 1984;47:2153.
29. Sutton MG, Sheps SG, Lie JT. Prevalence of clinically
unsuspected pheochromocytoma: review of a 50-year
autopsy series. Mayo Clin Proc. 1981;56:354.
30. Proye C, Fossati P, Fontaine P, et al. Dopamine secreting
pheochromocytoma: an unrecognised entity? Classification of pheochromocytomas according to their type of
secretion. Surgery. 1986;100:1154.
31. Kebebew E, SipersteinAE, Clark OH, DuhQY. Resultsof
laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms. Arch Surg.
2002;137(8): 948–53.
32. Aso Y, Homma Y. A survey on incidental adrenal
tumors in Japan. J Urol. 1992;147:1478.
33. Ito T, Imai T, Kikumori T, Shibata A, Horiba T, Kobayashi H, Sawaki M, Watanabe R, Nakao A, Kiuchi T.
Adrenal incidentaloma: review of 197 patients and
report of a drug-related false-positive urinary normetanephrine result. Surg Today. 2006;36(11):961–5.
34. Terzolo M, Ali A, Osella G, et al. Prevalence of adrenal
carcinoma among incidentally discovered adrenal
masses: a retrospective study from 1989 to 1994. Gruppo
Piemontese Incidentalomi Surrenalici. Arch Surg.
1997;132:8, 14.
35. Yamakita N, Saitoh M, Mercado-Asis LB, et al. Asymptomatic adrenal tumor: 38 cases in Japan including
seven of our own. Endocrinol Jpn. 1990;37:671.
36. Fernadez-Real JM, Gonzalbez J, Ricart W. Metabolic
abnormalities in patients with adrenal incidentaloma
[Letter to the Editor]. J Clin Endocrinol Metab.
2001;86(2): 950–1.
37. Terzolo M, Osella G, Ali A, et al. Subclinical Cushing’s
syndrome in adrenal incidentaloma. Clin Endocrinol
(Oxf). 1998;48:89.
38. Chidiac RM, Aron DC. Incidentalomas: a disease of
modern technology. Endocrinol Metab Clin North Am.
1997;26:233.
39. Beuschlein F, Borgemeister M, Schirra J, Goke B,
Fassnacht M, Arlt W, Allolio B, Reincke M. Oral
glucose tolerance testing but not intravenous glucose
administration uncovers hyper-responsiveness of
hypothalamo-pituitary-adrenal axis in patients with
adrenal incidentalomas. Clin Endocrinol. 2000;52(5):
617–23.
40. Barzon L, Scaroni C, Sonino N, et al. Incidentally discovered adrenal tumors: endocrine and scintigraphic
correlates. J Clin Endocrinol Metab. 1998;83:55.
41. Ito Y, Obara T,Okamoto T et al. Efficacy of single-voided
urine metanephrine and normetahephrineassayfor diagnosing pheochromocytoma. World J Surg. 1998;22:684.
42. Lee JA, Zarnegar R, Shen WT, Kebebew E, Clark OH,
Duh QY. Adrenal incidentaloma, borderline elevations of
urine or plasma metanephrine levels, and the ‘‘subclinical’’ pheochromocytoma. Arch Surg. 2007;142(9):870–4.
43. Linos DA. Management Approaches to adrenal incidentalomas (adrenalomas). A view from Athens, Greece.
Endocrinol Metab Clin North Am. 2000;29(1):141–57.
44. Gordon RD, Ziesak MD, Tunny TJ, et al. Evidence that
primary aldosteronism may not be uncommon: 12%
incidence among antihypertensive drug trial volunteers.
Clin Exp Pharmacol Physiol. 1993;20:296.
45. Gordon R, Stowasser M, Rutherford J. Primary Aldosteronism: are we diagnosing and operating on too few
patients? World J Surgery. 2001;25:941–7.
46. Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y,
Bornstein SR. The clinically inapparent adrenal mass:
update in diagnosis and management. Endocr Rev.
2004;25(2):309–40.
47. Schteingart DE. Management approaches to adrenal
incidentalomas. A view from Ann Arbour, Michigan.
Endocrinol and Metab Clin North Am. 2000;29(1): 127–39.
48. Linos DA, Avlonitis VS, Iliadis K. Laparoscopic resection of solitary adrenal metastasis from lung carcinoma:
a case report. J Soc Laparoendoscopic Surg. 1998;2:291.
49. Linos DA, Stylopoulos N. How accurate is computed
tomography in predicting the real size of adrenal
tumors? Arch Surg. 1997;132:740.
50. Fajardo R, Montalvo J, Vela´zquez D, Arch J, Bezaury P,
Gamino R, Herrera MF. Correlation between radiologic
and pathologic dimensions of adrenal masses. World J
Surg. 2004;28(5):494–7.
51. Yun M, Kim W, AlnafisiN, Lacorte L, Jang S, Alavi A. 18
F-FDG PET in characterizing adrenal lesions detected
on CT or MRI. J Nucl Med. 2001;42(12):1795–9.
52. Frilling A, Tecklenborg K, Weber F, Ku¨hl H, Mu¨ller S,
Stamatis G, Broelsch C. Importance of adrenal incidentaloma in patients witha historyof malignancy. Surgery.
2004;136(6):1289–96.
53. Silverman SG, Mueller PR, Pinkey LP, et al. Predictive
value of image-guided adrenal biopsy: Analysis and
results of 101 biopsies. Radiology. 1993;187:715.
54. Wachenfeld C, Beuschlein F, Swermann O, Mora P,
Fassnacht M, Allolio B, Reincke M. Discerning malignancy in adrenocortical tumors: are molecular markers
useful? Eur J Endocrinology. 2001;145: 335–41.
55. Libe`R, Fratticci A, Bertherat J. Adrenocortical cancer:
pathophysiology and clinical management. Endocr
Relat Cancer. 2007;14(1):13–28.
56. Reincke M, Beuschlein F, Slawik M, Borm K. Molecular
adrenocortical tumourgenesis. Eur J Clin Invest.
2000;30(53):63–68.
57. Bu¨low B, Jansson S, Juhlin C, Steen L, Thore´nM,
Wahrenberg H, Valdemarsson S, Wa¨ngberg B, Ahre´nB.
Adrenal incidentaloma – follow-up results from a
Swedish prospective study. Eur J Endocrinol. 2006;
154(3):419–23.
58. Nawar R, Aron D. Adrenal incidentalomas – a continuing management dilemma. Endocr Relat Cancer.
2005;12(3):585–98.
Brunaud
59.
Duh QY. Observation or laparoscopic adrenalectomy
for adrenal incidentaloma? A surgical decision analysis.
Med Sci Monit. 2006;12(9):CR355–62.
60. Barzon L, ScaroniC, Sonino, et al. Riskfactors and longterm follow-up of adrenal incidentalomas. J Clin Endocrinol Metab. 1999;84:520.
61. Grossrubatscher E, Vignati F, Posso M, Lohi P. The
natural history of incidentally discovered adrenocortical
Kebebew E, Sebag F, Zarnegar R, Clark OH,
L,
426
ENDOCRINE SURGERY
adenomas: a retrospective evaluation. J Endocrinol
Invest. 2001;24(11):846–55.
62. Linos DA. Surgical approach to the adrenal gland. In:
van Heerden JA, editor. Common problems in endocrine surgery: recommendations of the experts.
St. Louis: Year Book Medical; 1989. 349–55.
63. Linos DA, Stylopoulos N, Boukis M, et al. Anterior, posterior or laparoscopic approach for the management of
adrenal diseases? Am J Surg. 1997;173:120.
64. Gagner M, Pomp A, Heniford BT, et al. Laparoscopic
adrenalectomy: lessons learned from 100 consecutive
procedures. Ann Surg. 1997;226:238.
65. Lanzi R, Montorsi F, Losa M, et al. Laparoscopic
bilateral adrenalectomy for persistent Cushing’s
disease after transsphenoidal surgery. Surgery.
1998;123:144.
66. Miccoli P, Raffaelli M, Berti P, Materazzi G, Massi M,
Bernini G. Adrenal surgery before and after the introduction of laparoscopic adrenalectomy. Br J Surg.
2002;89(6):779–82.
67. Waltz MK, Alesina PF, Wenger FA, Deligiannis A,
Szuczik E, Peterson S, et al. Posterior retroperitoneoscopic adrenalectomy- results of 560 procedures in 520
patients. Surgery. 2006;140(6):943–948.
68. Walz MK, Gwosdz R, Levin SL, Alesina PF, Suttorp AC,
Metz KA, et al. Retroperitoneoscopic adrenalectomy
in Conn’s syndrome caused by adrenal adenomas or
nodular hyperplasia. World S Surg. 2008;32(5):847–53.
32
Adrenal Metastases and Rare Adrenal Tumors
Arsalla Islam and Fiemu E. Nwariaku
that of colorectal carcinoma. Also, the adrenal
Introduction
With the improved sensitivity of hormonal
assays and safety of laparoscopic adrenalectomy,
the outcomes for patients with functioning, nonmalignant adrenal tumors are excellent. Benign
(nonfunctioning) adrenal adenomas and metastases however comprise the most common incidentally – discovered tumors of the adrenal
gland. Adrenal metastases are present in
approximately 27% of postmortem examinations of patients with malignant neoplasms of
epithelial origin [1, 2]. Primary neoplasms of
the lung, breast, melanoma, kidney, and gastrointestinal tract are most commonly associated
with adrenal metastases [1–3]. Lung cancer and
melanoma represent the most common tumor
types associated with adrenal metastases.
Autopsy series have reported adrenal gland
metastases in 10–59% of patients with nonsmall-cell lung cancer [1, 4]. Adrenal metastases
are found in 50% of cases of malignant melanoma [5]. This very high incidence was also
shown in another series of 216 patients where
46.8% had either unilateral or bilateral adrenal
metastases [6]. This study demonstrated that the
adrenal gland is the sixth most common site of
distant metastases from melanoma [after lymph
nodes (73.6%), lungs (71.3%), liver (58.3%),
brain (54.6%), and bone (48.6%)]. This series
also showed that the incidence of adrenal metastases from malignant melanoma was threefold
gland is the second most common site of metastasis from hepatocellular carcinoma [7].
The declining mortality rates for patients
with these primary tumors portend a situation
where metastases in general and adrenal metastases in particular will become more common.
These metastases are also likely to be discovered
earlier because of more frequent surveillance,
and more sensitive imaging techniques such as
positron emission tomography (PET). Hence,
there is a need for better understanding of the
issues associated with the management of such
patients, especially the choice of biochemical
and imaging tests and appropriate therapy.
Most metastases to the adrenal gland are discovered during surveillance imaging in patients
with a personal history of cancer. Kloos and colleagues reported that 32–72% of incidentally discovered adrenalmasses in patients with ahistory of
cancer were metastases [8]. Others have found
similar rates, reporting that about half of adrenal
masses in 91 patients with a recently diagnosed
extra-adrenal malignancy were metastatic, whereas
48% were primaryadrenal lesions, includingpheochromocytoma and cortical adenomas [9]. The
median duration from diagnosis of the primary
cancer to the identification of adrenal metastases
is approximately 2.5 years, although adrenal
metastases have been discovered up to 22 years
after initial treatment of primary tumors [10].
These observations suggest that hormonal
evaluation should precede other imaging or
J.G.H. Hubbard et al. (eds.), Endocrine Surgery, Springer Specialist Surgery Series,
DOI 10.1007/978-1-84628-881-4_32, Ó Springer-Verlag London Limited 2009
427
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ENDOCRINE SURGERY
biopsy in patients with a personal history of
malignancy and an incidental adrenal mass.
Decisions regarding adrenalectomy in patients
with a nonfunctioning adrenal mass can then be
based on factors such as the presence of other
sites of metastases, the patient’s medical status,
and the predicted survival rate from their primary malignancy. Adrenalectomy in this context is associated with prolonged survival, albeit
in a highly selected group of patients. Furthermore the laparoscopic approach has been
shown to be safe in this patient population.
In this chapter, we discuss the evaluation
of patients with adrenal metastases. In particular, we review the biochemical evaluation,
imaging techniques, and indications for adrenalectomy. A discussion of rare adrenal tumors is
also included to provide insight into the management of these uncommonly encountered
tumors.
Biochemical Evaluation
Almost half of the adrenal tumors identified in
patients with a personal history of malignancy
are biochemically functioning. Therefore, the
appropriate biochemical evaluation of these
patients is necessary to guide therapeutic decisions. All patients should undergo biochemical
evaluation for cortical and medullary hyperfunction prior to further imaging, biopsy, and
treatment. In the largest series of incidental
adrenal masses, which included 1,096 cases
over a 15-year period, the majority of tumors
(74%) were nonsecretory adenomas, whereas
14.8% were hypersecretory and 4% were primary adrenal carcinomas. Among the hypersecretory tumors, 9.2% were cortisol-secreting
adenomas, 4.2% were pheochromocytomas,
and 1.4% were aldosteronomas [11]. However,
Lenert et al. demonstrated that about half of
adrenal masses in patients with a personal history of extra-adrenal malignancy were metastatic, whereas 48% were primary adrenal
lesions [9].
We previously described a preferred algorithm for the biochemical evaluation of adrenal
hyperfunction [12], Tests of cortical and medullary hyperfunction should include 24-h measurements of urinary free cortisol (UFC) and a
dexamethasone suppression test, as well as
plasma or urinary metanephrine measurements. These sensitive biochemical tests are
detailed in Table 32.1.
The normal range of UFC in most assays is
between 220 and 330 nmol/24 h (80–120 mg/24 h)
[13]. Although it is a highly sensitive test, there
are occasional problems with adequacy of urine
collection and cross-reactivity with exogenous
glucocorticoids. These can be prevented by giving patients adequate written instructions [14].
There remains a small but finite false-negative
rate. One study found a false-negative rate of
5.6% and a false-positive rate of 3.3% in combined data from 479 individuals [15]. Expressing
UFC over creatinine allows the adequacy of
Table 32.1. Biochemical evaluation for cortical and medullary hyperfunction
Biochemical study Sensitivity and specificity References
Tests of adrenal
cortical function
Tests of adrenal
medullary
function
24-h urinary free cortisol Sensitivity: 100%
Specificity: 98%
1 mg dexamethasone-suppression
test
Plasma aldosterone activity
to renin ratio (PAC:PRA
> 30 + PAC > 20 ng/dl)
24-h urinary metanephrines Sensitivity: 98% Lenders JW [23]
Plasma metanephrines Sensitivity: 97–100% Eisenhofer G [25]
Sensitivity: 97–100% Yanovski JA [18]
Sensitivity: 90%
Specificity: 91%
Mengden T, et al. [17]
Hankin ME [19]
Kennedy L [20]
Weinberger MH, et al. [22]
429
ADRENAL METASTASES AND RARE ADRENAL TUMORS
collection to be established and improves the
specificity [16], although it should be noted that
creatinine may vary with changes in lean body
mass. In another study [17], UFC measurement
was shown to have a diagnostic sensitivity and
specificity of 100 and 98%, respectively.
Using radioimmunoassays for serum cortisol
measurement has improved test sensitivity to
about 97–100% [18–20].
Screening for the adrenal cortical hyperfunction should also include the measurement of
plasma aldosterone concentration (PAC) and
estimation of plasma renin activity (PRA) to
exclude primary aldosteronism (PA). In addition to documenting an elevated ratio of plasma
aldosterone to PRA (>20), an elevated plasma
aldosterone should be present (>15 ng/dl) [21].
For the diagnosis of PA, a PAC to PRA ratio of
>30 plus a PAC >20 ng/dl is associated with a
sensitivity and specificity of 90 and91%, respectively [22].
Plasma metanephrines or 24-h urinary metanephrines have a reported sensitivity in the
range of 97–100% [23–26]
Imaging Adrenal Metastases
Computerized Tomography Scan
Abdominal computerized tomography (CT) scan
is the preferred method for assessing the size and
characteristics of adrenal masses. CT is fast,
readily available, and offers the highest spatial
resolution. Adrenal adenomas are usually small,
well-defined homogeneous lesions with clear
margins and large intralesional lipid content.
Large tumor size, irregular shapes, vague contour, invasion into surrounding structures, and
high values onnonenhanced CT aresuggestive of
malignancy [27]. Incidental adrenal lesions are
now found in up to 5% of scans.
Benign adrenal masses consist predominantly of intracellular lipid (composed mainly
of cholesterol, fatty acids, and neutral fat),
whereas malignant lesions contain less intracytoplasmic fat. This property has been used to
differentiate adenomas from nonadenomas on
CT and magnetic resonance imaging (MRI)
scans. Such intralesional fat can be quantified
by low attenuation values [Hounsfield units
(HU)] on nonenhanced CT in patients with
benign adenomas. Both CT and MRI can
reliably characterize intralesional fat content.
There is an inverse linear relationship between
the intracytoplasmic fat content of an adrenal
adenoma and the CT attenuation value measured as Hounsfield units [28]. Nonadenomatous lesions have higher CT density values
because their cytoplasm is relatively lipidpoor. A CT scan attenuation value <10 HU or
visual detection of a diffuse decrease in relative
signal intensity (SI) (relative to spleen) suggests
a lipid-containing benign adenoma with a specificity of more than 95% and a sensitivity of
nearly 80% [29]. Although rare, metastases have
uncommonly been reported in lesions that measure less than 10 HU [30].
An analysis of pooled data from 10 studies
recommended 10 HU as a reasonable cutoff to
differentiate benign from nonbenign tumors
[29]. This low threshold although sensitive is
not very specific. However this may be an acceptable trade off to prevent the misdiagnosis of a
malignant adrenal tumor as benign. A limitation
of this approach is that most adrenal masses are
of intermediate density (10–40 HU) range, which
would lead to further diagnostic tests in most
patients. Furthermore, most routine abdominal
CT scans are performed with intravenous contrast, thus rendering interpretation of density
values difficult. In order to minimize these limitations, the rate of contrast washout has been
used as a surrogate to differentiate benign from
malignant masses. The rate of washout of intravenous contrast agents is slower in nonadenomas compared with adenomas. Korobkin et al.
[31] note that adenomas washout rates were 51%
at 5 min and 70% at 15 min, with sensitivity and
specificity of 96%. In another study of 78 lesions
[32], all benign adrenal adenomas had density
measurements less than 37 HU, whereas all nonadenomas had density measurements greater
than 41 HU, 30 min after intravenous contrast
administration. Another study [31] showed
that no malignant lesions had a density of less
than 25 HU at a 15-min delay. This allows for
100% specificity with only minimal interruption
of the patient flow in the CT scanner. As such
we recommend the use of dedicated CT protocols with washout analyses in the evaluation
of incidental masses. Our adrenal CT protocol
uses 2-mm noncontrast, dynamic (60 s)
images, followed by 10 min delayed imaging
through the adrenals. Figures 32.1–32.3 show
bilateral adrenal metastases in a patient with