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22 Adrenocortical Carcinoma andAdrenal Metastasis
Table 22.2 Initial biochemical evaluation of adrenal masses
Laboratory tests
CBC, metabolic panel, coagulation prole, liver function panel
Plasma or 24-h urine metanephrine and normetanephrine levels
ACTH, aldosterone, renin, DHEA-S, 11-deoxycortisol, testosterone, estradiol, 17-OH
progesterone. 1mg dexamethasone suppression test in those without overt signs of Cushing
syndrome. 24-h urine for cortisol in those with over signs of Cushing syndrome
199
Imaging Studies [9–11]
• ACCs at presentation are typically 7–10cm, are characterized by low lipid content, and have delayed contrast washout.
• An adrenal protocol CT is the preferred initial imaging study. MRI can help differentiate benign from malignant lesions in addition to better evaluating for vascular invasion, presence of intravenous tumor thrombus, and liver metastases.
• Characteristics increasing risk for malignancy include: size >4cm, Hounseld
units >10 on non-contrast phase, washout %<50–60%, heterogeneous appearance, irregular borders, calcications or necrosis, vascular thrombus, direct invasion of adjacent structures, and/or presence of lymphadenopathy.
• If an adrenal mass is indeterminate following all evaluation, the mass can be
treated as ACC from the standpoint of operative approach and technique.
• Chest CT +/− 18F-2-deoxy-d-glucose positron emission tomography (18FDGPET) CT should be obtained preoperatively in cases of known or likely ACC to
assess for metastatic disease as this will often change the treatment plan.
Fine-Needle Aspiration (FNA) Evaluation [12–14]
• FNA of adrenal masses is not usually performed as it has limited ability to distinguish between benign and malignant tumors of adrenocortical origin and may
promote seeding of the needle tract. Indications for FNA include: (1) poor operative candidates with non-functional tumors needing a tissue diagnosis to guide
medical therapy; (2) non-functional borderline or unresectable ACC that will be
treated medically to attempt to improve resectability; (3) suspected metastatic
disease involving the adrenal gland(s) by a malignancy of non-adrenal origin
with no other sites amenable to biopsy; (4) concern for lymphoma or retroperitoneal sarcoma.
• Pheochromocytoma must be ruled out prior to biopsy of any adrenal (or paraaortic/paracaval) tumor.
200
N. Owusu-Brackett and B. S. Miller
Staging [3, 15]
• The American Joint Committee on Cancer (AJCC) and the European Network
for the Study of Adrenal Tumors (ENSAT) are the two most commonly used
staging systems.
• 50% of ACC patients present with Stage IV disease at diagnosis.
Treatment [3, 16]
• Surgery is the only treatment modality alone that can achieve cure. Open transabdominal adrenalectomy remains the approach of choice. It is critically important to achieve negative margins. If it is suspected that gross residual disease will
remain, neoadjuvant chemotherapy should be considered prior to resection.
• Control of hormone excess is important to facilitate treatment. Table22.3 lists
available medications according to the type of hormone excess.
• Systemic options for therapy are limited. Mitotane is the only FDA-approved
drug specic to ACC.First-line combination chemotherapy includes etoposide,
doxorubicin, and cisplatin. Second-line chemotherapy has been streptozocin and
5-uorouracil, but more recently immunotherapeutic options have also
been chosen.
Metastasis totheAdrenal Gland
Overview [17–19]
• Any type of malignancy can theoretically metastasize to the adrenal gland; the
most common are lung, renal cell, breast, melanoma, and lymphoma.
• Metastasis to the adrenal glands spreads primarily through the blood due to the
rich sinusoidal blood supply of the adrenal glands.
Table 22.3 Medications to control adrenal hormone excess
Hormone Mechanism of action Medication
Cortisol Inhibits
11-beta-hydroxylase
Cortisol receptor blocker Mifepristone
Aldosterone MR antagonist
Antikaliuretic-diuretic
Estrogens Aromatase inhibitor Anastrozole
Androgens Androgen receptor
inhibitor
Metyrapone, ketoconazole, Mitotane, Osilodrostat,
etomidate
Spironolactone, Eplerenone
Amiloride
Spironolactone, Eplerenone
22 Adrenocortical Carcinoma andAdrenal Metastasis
201
Evaluation
History/Physical Examination
• Patients should undergo comprehensive assessment for malignancy (prior or
known current diagnosis, signs/symptoms of an undiagnosed malignancy,
delayed or new diagnosis).
• Family history of malignancy may suggest a germline mutation leading to malignancy and metastasis.
• Most adrenal metastases are asymptomatic and found at initial diagnosis of a
malignancy or during surveillance. With large metastases, local symptoms of
compression may develop.
• With involvement of both adrenal glands, signs/symptoms of adrenal insufciency may develop [20].
Imaging [21–24]
• Many metastases to the adrenal gland are identied during the course of surveillance. If identied on positron emission tomography (PET), standard uptake values may be consistent with the primary tumor and indicative of metastasis to the
adrenal. Further dedicated adrenal imaging may not be required if it is clear the
adrenal lesion is a metastasis.
• If it is not clear that an adrenal mass is a metastasis, an adrenal protocol CT is the
preferred initial imaging study. PET CT is also reasonable. Some malignancies
are not FDG avid (e.g., renal cell cancer).
FNA Evaluation
• FNA has a limited role but can be considered in the setting of unresectable disease to guide systemic therapy or diagnostic uncertainty if resection is not going
to be pursued.
• With known isolated adrenal metastases, literature exists to support proceeding
with adrenalectomy and avoiding FNA.
202
N. Owusu-Brackett and B. S. Miller
Treatment [25]
• Surgical indications include: (1) isolated adrenal metastatic disease; and (2)
those with concern that the adrenal tumor will progress and invade adjacent
structures when other disease is controlled. Adrenalectomy for singular adrenal
metastatic disease has been associated with improved long-term survival.
• Patients with multiple sites of metastatic disease may be better served with other
treatment modalities such as radiation or chemotherapy.
References
1. Kerkhofs TM, Verhoeven RH, Bonjer HJ, etal. Surgery for adrenocortical carcinoma in The
Netherlands: analysis of the national cancer registry data. Eur J Endocrinol. 2013;169(1):83–9.
2. Fassnacht M, Libe R, Kroiss M, Allolio B.Adrenocortical carcinoma: a clinician's update. Nat
Rev Endocrinol. 2011;7(6):323–35.
3. Fassnacht M, Dekkers OM, Else T, etal. European Society of Endocrinology Clinical Practice
Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the
European network for the study of adrenal tumors. Eur J Endocrinol. 2018;179(4):G1–G46.
4. Berruti A, Baudin E, Gelderblom H, etal. Adrenal cancer: ESMO clinical practice guidelines
for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:131–8.
5. Petr EJ, Else T.Genetic predisposition to endocrine tumors: diagnosis, surveillance and challenges in care. Semin Oncol. 2016;43(5):582–90.
6. Else T, Kim AC, Sabolch A, etal. Adrenocortical carcinoma. Endocr Rev. 2014;35(2):282–326.
7. Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J.Cortisol as a marker
for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol
Metab. 2014;99(12):4462–70.
8. Bancos I, Alahdab F, Crowley RK, et al. Therapy of endocrine disease: improvement of
cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis. Eur J Endocrinol.
2016;175(6):R283–95.
9. Caoili EM, Korobkin M, Francis IR, Cohan RH, Platt JF, Dunnick NR, Raghupathi KI.Adrenal
masses: characterization with combined unenhanced and delayed enhanced CT.Radiology.
2002;222(3):629–33.
10. Caoili EM, Korobkin M, Francis IR, Cohan RH, Dunnick NR.Delayed enhanced CT of lipidpoor adrenal adenomas. AJR Am J Roentgenol. 2000;175(5):1411–5.
11. Haider MA, Ghai S, Jhaveri K, Lockwood G.Chemical shift MR imaging of hyperattenuating
(>10 HU) adrenal masses: does it still have a role? Radiology. 2004;231:711–6.
12. Khan TS, etal. 11C-metomidate PET imaging of adrenocortical cancer. Eur J Nucl Med Mol
Imaging. 2003;30:403–10.
13. Fassnacht M, ArltW BI, etal. Management of adrenal incidentalomas: European Society of
Endocrinology Clinical Practice Guideline in collaboration with the European network for the
study of adrenal tumors. Eur J Endocrinol. 2016;175(2):G1–G34.
14. Bancos I, Tamhane S, Shah M, Delivanis DA, Alahdab F, Arlt W, Fassnacht M, Murad
MH.Diagnosis of endocrine disease: the diagnostic performance of adrenal biopsy: a systematic review and meta-analysis. Eur J Endocrinol. 2016;175(2):R65–80.
15. Amin MB, Greene FL, Edge SB, etal. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more "personalized" approach to cancer
staging. CA Cancer J Clin. 2017;67(2):93–9.
22 Adrenocortical Carcinoma andAdrenal Metastasis
16. Miller BS, Else T, Committee AAS.Personalized care of patients with adrenocortical carcinoma: a comprehensive approach. Endocr Pract. 2017;23(6):705–15.
17. Tsujimoto A, Ueda T, Kuge H, etal. Long-term survival after adrenal metastasectomy from
colorectal cancer: a report of two cases. Surg Case Rep. 2019;5:61.
18. Klikovits T, Lohinai Z, Fábián K, Gyulai M, Szilasi M, Varga J, Baranya E, Pipek O, Csabai I,
Szállási Z, Tímár J, Hoda MA, Laszlo V, Hegedűs B, Renyi-Vamos F, Klepetko W, Ostoros G,
Döme B, Moldvay J.New insights into the impact of primary lung adenocarcinoma location
on metastatic sites and sequence: a multicenter cohort study. Lung Cancer. 2018;126:139–48.
19. Blažeković I, Jukić T, Granić R, Punda M, Franceschi M.An unusual case of papillary thyroid
carcinoma Iodine-131 avid metastasis to the adrenal gland. Acta Clin Croat. 2018;57(2):372–6.
20. Kung AW, Pun KK, Lam K, Wang C, Leung CY.Addisonian crisis as presenting feature in
malignancies. Cancer. 1990;65:177–9.
21. Elsayes KM, et al. Adrenal masses: MR imaging features with pathologic correlation.
Radiographics. 2004;24(Suppl. 1):S73–86.
22. Caoili EM, Korobkin M, Brown RK, Mackie G, Shulkin BL.Differentiating adrenal adenomas
from nonadenomas using (18)F-FDG PET/CT: quantitative and qualitative evaluation. Acad
Radiol. 2007;14(4):468–75.
23. Groussin L, etal. 18F-Fluorodeoxyglucose positron emission tomography for the diagnosis of
adrenocortical tumors: a prospective study in 77 operated patients. J Clin Endocrinol Metab.
2009;94:1713–22.
24. Leboulleux S, et al. Diagnostic and prognostic value of 18-uorodeoxyglucose positron
emission tomography in adrenocortical carcinoma: a prospective comparison with computed
tomography. J Clin Endocrinol Metab. 2006;91:920–5.
25. Romero Arenas MA, Sui D, Grubbs EG, Lee JE, Perrier ND. Adrenal metastectomy is
safe in selected patients. World J Surg. 2014;38(6):1336–42. https://doi.org/10.1007/
s00268- 014- 2454- x.
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Chapter 23
Minimally Invasive Adrenalectomy:
Techniques andPotential Complications
NaEunKim andMashaJ.Livhits
Anatomy
– The adrenal glands are retroperitoneal paired organs that are found superior and
medially to the bilateral kidneys.
– They are the third most perfused organ in the body, after the kidney and thyroid.
– The adrenal glands are made of the adrenal cortex and medulla which have dif-
ferent embryologic origins. The adrenal cortex is made of three layers: zona
glomerulosa, zona fasciculata and zona reticularis. The adrenal medulla is made
of chromafn cells which release catecholamines.
– The right adrenal gland sits lateral to the retrohepatic inferior vena cava (IVC).
The right adrenal vein drains directly into the IVC.The left adrenal gland lies
between the left kidney and the aorta. The left adrenal vein joins the inferior
phrenic vein before draining into the left renal vein. There can be anatomic vari-
ants of the adrenal vein, especially in the case of a large right-sided
pheochromocytoma.
Diseases oftheAdrenal Gland
– An adrenal mass can be found incidentally during an imaging procedure done for
another indication. These incidentalomas are found in up to 5% of patients
undergoing CT scans.
N. E. Kim (*) · M. J. Livhits
Section of Endocrine Surgery, David Geffen School of Medicine at UCLA,
Los Angeles, CL, USA
e-mail: naeunkim@mednet.ucla.edu; mlivhits@mednet.ucla.edu
Switzerland AG 2024
R. M. Gartland, J. A. Lee (eds.), Endocrine Surgery Clerkship, Contemporary
Surgical Clerkships, https://doi.org/10.1007/978-3-031-62091-1_23
205© The Author(s), under exclusive license to Springer Nature
206
N. E. Kim and M. J. Livhits
– Imaging characteristics of adrenal masses can provide valuable information.
Benign adrenal neoplasms are typically less than 4cm, have smooth borders, and
are homogeneous. Malignant neoplasms are often greater than 6cm at the time
of discovery, have irregular borders, and are heterogeneous. In addition, benign
adrenal neoplasms are lipid-rich and less than 10 Hounseld on non-contrast CT
imaging.
– Workup of an adrenal mass should include determining the functional status.
This can be obtained with a history and physical and with biochemical workup.
– Diseases of the adrenal cortex including primary hyperaldosteronism, due to
excess secretion of aldosterone from one or both adrenal glands; autonomous
hypercortisolism or Cushing’s syndrome, due to excess glucocorticoid release;
and adrenocortical carcinoma, a rare malignant tumor that should be resected
with an open approach with en bloc resection of any invaded organs. Figure23.1
shows a gross specimen of a 0.6cm aldosterone-producing right adrenal nodule
in the adrenal cortex.
– Disease of the adrenal medulla includes pheochromocytoma due to excess cate-
cholamine release. Figure23.2 shows a CT image of a right adrenal mass, bio-
chemically consistent with a pheochromocytoma. Figure 23.3 shows a gross
specimen of a pheochromocytoma.
Fig. 23.1 Gross specimen
of 0.6cm aldosteroneproducing right adrenal
nodule in the adrenal
cortex
23 Minimally Invasive Adrenalectomy: Techniques andPotential Complications
Fig. 23.2 CT image of a
right adrenal mass,
biochemically consistent
with a pheochromocytoma
Fig. 23.3 Gross specimen
of pheochromocytoma
207
208
N. E. Kim and M. J. Livhits
Minimally Invasive Approach
– Advantages of laparoscopic adrenalectomy include reduced length of hospital-
ization, reduced postoperative pain, and reduced operative blood loss and com-
plication rate [1].
– The laparoscopic transabdominal and retroperitoneoscopic approaches have
similar outcomes [2].
– The retroperitoneoscopic approach can be used in patients with a tumor smaller
than ~6cm or bilateral tumors. It is advantageous in patients with a history of
extensive prior abdominal surgery as it can avoid intra-abdominal adhesions [3].
– Retroperitoneoscopic adrenalectomy is technically more difcult in obese
patients (BMI> 35) due to the excess amount of periadrenal fat, which makes
orientation and location of the adrenal gland more challenging due to the lack of
anatomic landmarks. Older and obese male patients have a particularly difcult
body habitus for this technique. However, in experienced hands, retroperitoneo-
scopic adrenalectomy can be performed successfully in patients with BMI>35.
– Despite the advantages of the minimally invasive approaches, an open adrenalec-
tomy should be performed in cases in which adrenal malignancy is suspected
(e.g.,very large size, irregular borders, or other concerning imaging characteristics)
and at the discretion of the surgeon based on their experience and comfort level.
Techniques
– For the laparoscopic transabdominal approach, the patient is positioned in a lat-
eral decubitus position with the side of the lesion facing up. The table is exed to
widen the operative space between the costal margin and the iliac crest. Three to
four laparoscopic ports are placed inferior to the costal margin [4]. Figure23.4
Fig. 23.4 Lateral
decubitus patient
positioning for a
laparoscopic
transabdominal
adrenalectomy
23 Minimally Invasive Adrenalectomy: Techniques andPotential Complications
demonstrates the patient positioning and the laparoscopic port placement of the
laparoscopic transabdominal approach.
– For a left adrenal mass, the attachments of the spleen are taken down rst to
mobilize the spleen medially. The splenic exure of the colon is taken down if
necessary to mobilize the colon caudally. The “open book” technique is used to
open the space medial to the adrenal gland and lateral to the aorta. The left side
of the book is the spleen, tail of the pancreas, and the stomach. The right side of
the book is the kidney and adrenal gland. The inferomedial limb of the left adre-
nal gland often extends more than it does on the right side, which can make this
dissection more challenging.
– For a right adrenal mass, the triangular ligament of the liver is rst mobilized.
The “open book” technique is used, which separates the kidney and adrenal
gland (left side of the book) from the bare area of the liver (right side of the
book). It is important to be mindful of the right adrenal vein due to its short
course and direct entry into the IVC.
– For the retroperitoneoscopic approach, the patient is positioned prone with bol-
sters placed on the chest and pelvis to allow the abdominal girth to hang anteri-
orly. This technique allows for high insufation pressures with minimal risk of
hypercapnia or air embolus [5]. Figure23.5 demonstrates the patient positioning
for the retroperitoneoscopic approach. Figure23.6 demonstrates the port place-
ment for this approach.
– Mobilization of the lateral aspect of the kidney allows it to retract inferiorly to
expose the adrenal gland. The right adrenal vein is identied as it directly enters
the IVC.The left adrenal vein can be identied by tracing the inferior phrenic
vein. Once the vein is divided, the adrenal gland is then dissected from the peri-
adrenal fat.
– For either approach, the adrenal gland is removed with a rim of peri-adrenal fat
to avoid capsular disruption.
209
Fig. 23.5 Prone patient
positioning for a
retroperitoneoscopic
adrenalectomy