This document provides an overview of adrenal gland anatomy and pathology. It describes the location, structure, and functions of the adrenal cortex and medulla. It discusses various adrenal tumors including aldosteronomas, Cushing's syndrome, and virilizing/feminizing tumors. Diagnosis, evaluation, and treatment of these conditions are explained. Surgical approaches for adrenalectomy are outlined.

1. By
Ihab Samy Fayek
Lecturer of Surgical Oncology
National Cancer Institute
Cairo University
2010
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2. Adrenal (suprarenal) Anatomy
•First described in 1563 by Eustachius.
•Located above (or attached to) the upper pole
of the kidney in the retroperitoneum
• Each normally weighs only 5 to 7 grams.
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4. • They are unequally divided into:
Outer cortex (80%)
Inner medulla(20%)
• Despite their organization into a single gland, the
medulla and cortex are functionally different
endocrine organs, and have different
embryological origins.
• The medulla derives from ectoderm (neural
crest), while the cortex develops from mesoderm.
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5. • The adrenal cortex is partitioned into three concentric
zones of steroid-synthesizing cells
Glomerulosa  a mineralocorticoid (aldosterone) which
is responsible for the regulation of salt and water balance
in the body.
Fasciculata  a glucocorticoid (cortisol) which regulates
the level of carbohydrate in the body.
Reticularis  sex hormones (progesterone, oestrogen
precursors and androgens) which have a role in the
development of sexual characteristics.
• Although the boundaries between these zones are
somewhat indistinct, each has a characteristic
arrangement of cells.
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6. Adrenal Histology
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9. • The adrenal medulla,is a source of the
catecholamines epinephrine and
norepinephrine.
• The chromaffin cell (pheochromocyte) is the
principle cell type.
• The medulla is richly innervated by preganglionic
sympathetic fibers and is, in essence, an
extension of the sympathetic nervous system.
• Small number of sympathetic ganglion cells are
commonly observed in the medulla.
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10. Adrenal Medulla:
A Modified Sympathetic Ganglion
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11. • Classified according to:
Functional or non-functional status.
Benign or malignant features.
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12. • Can be stratified into one of several classes:
(1) A clinical syndrome caused by excess hormone
production from a functional tumor.
(2) Asymptomatic mass discovered "incidentally"
(usually during an abdominal CT scan).
(3) A large tumor causing local or regional
symptoms.
(4) An adrenal mass in the setting of a known
extraadrenal malignancy representing potential
metastatic disease.
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13. • Adrenocortical tumors include:
1-Aldosteronoma.
2-Cortisol-producing adenoma (Cushing's
syndrome).
3-Virilizing/feminizing adrenal tumors.
4-Adrenocortical carcinomas.
5-Adrenal metastases.
6-Nonfunctional adrenal adenomas
(incidentalomas).
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14. • Primary hyperaldosteronism  excess
aldosterone  suppresses plasma renin
activity (PRA).
• First described by Jerome Conn in 1955, the
syndrome, which bears his name.
• Consists of hypertension, weakness, and
polyuria.
• 80% Adenoma
15 -20% Bilateral Hyperplasia
< 1% Carcinoma
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15. Diagnosis
(1) hypertension and hypokalemia (a serum
potassium level less than 3.4 mEq/L).
(2) persistent hypertension refractory to medical
treatment.
(3) patients with an adrenal mass and
concurrent hypertension.
(4) An elevated plasma aldosterone
concentration (PAC ) with a suppressed
plasma renin activity (PRA) and PAC/PRA ratio
greater than 30  primary
hyperaldosteronism.
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16. (5) Elevated urinary aldosterone levels (greater
than 12 µg per day) during an aldosterone
suppression test, which involves administering
either a high-sodium diet or intravenous saline
infusion.
(6) CT scan of the adrenal glands is fairly
accurate in detecting unilateral adenomas
greater than 0.5 cm in diameter (mostly 0.5 -2
cm.).
(7) Adrenal hypertrophy as defined by the
adrenal width being greater than the width of
the diaphragmatic crura on CT scan 
Hyperplasia.
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17. Treatment
• Administration of spironolactone and
potassium supplements until serum potassium
is normalized.
• Antihypertensive medications until blood
pressure is controlled.
• Adenoma  Surgery
• Hyperplasia  Medical
• < 4 cm.  Laparoscopic adrenalectomy
• 4 cm. or more (carcinoma??)  open or
transabdominal approach.
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19. • In 1855, Addison described clinical features
present in patients with adrenal disease
identified at autopsy.
• Cushing described the clinical features of
hypercortisolism in 1912.
• The role of adrenal tumors in this syndrome was
not understood until 1934.
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20. • Exogenous Steroid therapy
• Endogenous or naturally occurring 
Benign (adrenal adenoma)
Malignant (adrenal carcinoma)  10% - 20%
Pituitary hyperplasia or adenoma  60 -70%
(Cushing's disease)
Benign or malignant nonadrenal tumor 
ectopic ACTH  10 - 20%
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21. Signs and Symptoms of Cushing's Syndrome
• General and Subjective
Central fat distribution, "buffalo hump"
Moon facies
Proximal muscle weakness/atrophy
Hypertension
Headaches and Depression
• Skin Changes
Wide, violaceous abdominal striae
Easy bruising
Hirsutism
Acne/hyperpigmentation
• Metabolic Derangements
Hypokalemic alkalosis
Glucose intolerance/diabetes
Polyuria
Nephrolithiasis
Osteopenia/osteoporosis
Immunosuppression/poor wound healing
Menstrual changes.
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22. Diagnosis
• Signs and Symptoms (range from mild to
severe)
• 24-hour urine-free cortisol (UFC)  both
sensitive (greater than 95%) and specific (98%).
• low-dose dexamethasone suppression test 
1 mg of dexamethasone is administered orally at 11:00 pm
Plasma cortisol level measured the following morning at 8:00 am.
Normally, dexamethasone suppresses cortisol excretion so that the
morning plasma levels are less than 5 µg per 100 ml.
Cortisol levels in patients with Cushing's syndrome, regardless of etiology, are
not suppressed by a single low dose of dexamethasone.
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23. • Differentiate between :
A corticotrophin-independent form caused by
adrenal lesions, and
A corticotrophin-dependent form resulting
from pituitary and ectopic sources of elevated
ACTH production.
Basal ACTH level
Low (usually less than 5pg/ml)  A corticotrophin-independent form
High (usually greater than 15 pg/ml)  A corticotrophin-dependent form
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24. • Differentiate between pituitary and ectopic
sources of elevated ACTH :
1- Very high levels of ACTH greater than 500 pg/ml are typically
indicative of ectopic ACTH syndrome.
2- High-dose dexamethasone suppression test  a single 8-mg
dose of dexamethasone given at midnight, with measurement
of UFC or plasma cortisol the following morning.
Plasma cortisol level decrease to less than 5 ng/dl and UFC
declines by 50% or more of baseline levels  Pituitary
dependent hypercortisolism
Serum and urinary cortisol levels not suppressed  ectopic ACTH
production
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25. • Imaging studies :
High-resolution CT scan or MRI abdomen  Adrenal
adenoma or a pancreatic islet cell tumor (if source of
ectopic ACTH secretion is not localized to the chest).
CT scan of the chest  bronchial carcinoids or small cell
lung cancers (the most common sources of ectopic
ACTH).
Gadolinium-enhanced MRI  pituitary adenomas.
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26. Computed tomography of a right cortical adenoma in a patient with Cushing's syndrome
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27. Treatment
• Preoperative stress doses of glucocorticoids,
as well as postoperative replacement therapy,
because the contralateral gland is often
suppressed.
• A typical regimen is 100 mg intravenous (IV)
hydrocortisone preoperatively, followed by
100 mg every 6 hours postoperatively. The
doses are gradually lowered until the patient
is able to take oral steroids. These are then
continued and tapered.
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28. • A single adrenal adenoma  laparoscopic
adrenalectomy is the procedure of choice.
• An adrenocortical carcinoma  Open approach
(bilateral subcostal, anterior midline, or thoraco-
abdominal incision).
• Bilateral pigmented micronodular adrenal
hyperplasia (rare)  bilateral adrenalectomy
(high morbidity).
• Pituitary tumors  transsphenoidal approach or
Pituitary irradiation (not a surgical candidate, for
palliation of unresectable tumors and for
recurrent tumors).
• Ectopic sources  complete resection ,debulking
or chemotherapy.
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30. • Virilizing tumors are relatively uncommon.
• Feminizing tumors are exceedingly uncommon.
• Most virilizing tumors (70% to 85%) are adrenal
cortical carcinomas.
• Most feminizing tumors, although less
common, appear more likely to be benign.
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31. Diagnosis
• Symptoms of hirsutism, scalp alopecia, and
irregular menses in a female.
• Symptoms of gonadal atrophy, gynecomastia,
impotence, and loss of libido in a male (examine
testis ?)  Estrogen ; FSH LH
• Mass with or without abdominal pain
(malignancy??).
• Baseline serum testosterone and
dihydroepiandrostendione (DHEAS) levels.
• 24-hour urine collection for 17-hydroxy and
ketosteroids.
• Abdominal CT scan  adrenal or ovarian mass.
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32. • Differentiate between virilizing ovarian mass as well as
"idiopathic“ non neoplastic virilizing syndrome AND virilizing
adrenal mass :
Dexamethasone suppression (DMS) testing
(sensitivity 100%)
5 days of 1 mg of DMS every 8 hours
Ovarian or nonneoplastic virilizing syndrome suppressed their
serum concentration of DHEAS and urinary 17-ketosteroids to
normal levels.
In all patients with an adrenal tumor as the source of elevated
androgens, DMS failed to suppress either DHEAS or 17-
ketosteroids
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33. Treatment
• Because of the high likelihood of these tumors
being an adrenocortical carcinoma (ACC) 
laparoscopic adrenalectomy is generally not
indicated.
• Adrenocortical carcinoma must be resected en
bloc with any involved surrounding structures
if the best chance for cure is to be obtained.
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34. • Rare endocrine malignancy (1% of adrenal masses).
• women : men = 2 : 1 Right and Left equal.
• 30% - 40%  Non-functioning (abdominal pain, increased
abdominal girth, weight loss, weakness, anorexia, and nausea)
• 50% - 60%  Functioning (hypercortisolism,
hyperaldosteronism, or virilization).
• 1% - 5%  Incidentaloma.
• Usually larger than 6 cm.
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35. DIAGNOSIS
• Rapidly progressive Cushing’s syndrome.
• Large (>6 cm) adrenal mass that extends to nearby
structures on CT.
• MRI is superior to CT in determining extension of the
tumor into the adrenal vein, renal vein, IVC and
diaphragmatic invasion  thoraco-abdominal approach
& veno-venous bypass.
• Metastatic evaluation with CT of the chest and bone
scan.
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36. TNM Staging Classification for Adrenocortical Carcinoma
(AJCC 2006)
T1 Tumor ≤5 cm, no invasion
T2 Tumor >5 cm, no invasion
T3 Tumor any size, locally invading adjacent fat
but not involving adjacent organs.
T4 Tumor any size, locally invading adjacent
organs (such as the kidney, pancreas, spleen, and
liver)
N0 No regional positive nodes
N1 Positive regional nodes
M0 No distant metastatic disease
M1 Distant metastatic disease (lung, lymph
nodes, liver, and bone).
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37. Stage TNM Criteria Percentage
of Cases
I T1 , N0 , M0 <5 cm; confined to adrenal 2
II T2 , N0 , M0 >5 cm; confined to adrenal 19
III T3 , N0 , M0
T1 /T2 , N1 , M0
Local invasion or positive nodes 18
VI T3 /T4 , N1 , M0
Any T/N, M1
Local invasion and positive nodes, or
metastases
61
Modified from Pommier RF, Brennan MF:
Management of adrenal neoplasms. Curr
Probl Surg 28:684, 1991.

38. Treatment
• Stage I and II tumors  Complete resection is the only
hope of cure (5-year survival may approach 40% to 60%).
• Stage III disease should also be resected, yet survival drops
to 20% to 30% with increased rates of local recurrence.
• Stage IV disease and obvious metastases have an average 1-
year survival of only 10%, so an operation may not provide
any benefit  MITOTANE
However, Debulking  in a hyperfunctioning tumor with
severe metabolic complications, such as Cushing's
syndrome and to palliate local symptoms such as pain or
intestinal obstruction.
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39. Surgery
Wide exposure and a generous incision are
needed for several reasons:
• Allow en bloc resection of tumor and adjacent
involved structures.
• Minimize the risk of rupture of the tumor
capsule with spillage.
• Permit access to the renal veins and vena cava
if tumor thrombus is present
• Provide exposure for aortocaval node
clearance.
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40. APPROACHES
(1) Anterior transabdominal.
(2) Posterior retroperitoneal.
(3) Thoracoabdominal.
(4) Laparoscopic TRANSABDOMINAL LATERAL APPROACH
RETROPERITONEAL APPROACH
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41. ANTERIOR APPROACH
(Transabdominal)
• Provides wide exposure and access to
both adrenals
• Allows staging of adrenal malignancies.
• The preferred route for resection of
large, potentially invasive adrenal
tumors.
• In patients with extremely large (>10 to
15 cm) adrenocortical carcinomas, the
bilateral subcostal incision can be
extended in the upper midline to the
xiphoid (Mercedes incision) to allow
improved exposure and mobilization of
the liver.
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42. Resection of the right adrenal (Ant. Approach)
• The right triangular ligament is mobilized and the liver is gently retracted
superiorly and medially.
• The hepatic flexure and transverse colon are mobilized and are retracted
medially.
• A Kocher maneuver of the duodenum is performed.
• Dissection of the gland proceeds from its superomedial aspect.
• The vena cava is carefully dissected along its posterolateral border.
• The right adrenal vein often enters the IVC posteriorly.
• Accessory venous drainage into the IVC is often encountered along the
medial border of the tumor, due to neovascularization.
• Local invasion into the renal parenchyma, diaphragm, and less commonly
the hepatic parenchyma necessitates en bloc resection.
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43. Resection of the left adrenal gland (Ant. Approach)
• The left colon is freed and reflected
inferiorly.
• The spleen is then delivered from the left
upper quadrant medially by dividing the
splenorenal ligament.
• Opening the gastrocolic ligament exposes
the inferior border of the pancreas.
• The spleen, stomach, and pancreatic tail are
retracted medially en bloc (Cattell maneuver
= medial visceral rotation) to expose the left
kidney and adrenal
• The left adrenal vein exits the gland along
the inferomedial border of the tumor and
enters the left renal vein.
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44. POSTERIOR APPROACH
(Retroperitoneal)
• A hockey stick-type incision in
the back with resection of the
12th rib.
• Small, unilateral tumors.
• Almost completely replaced by
laparoscopic adrenalectomy.
• The only indication currently is
the patient with a small (<5 cm)
tumor who has contraindications
to laparoscopy.
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46. • The thoracoabdominal approach is seldom employed.
• Most often used with very large, malignant tumors with IVC
extension or diaphragmatic invasion when en bloc resection is
necessary.
• The patient is positioned in a slight lateral angle.
• The incision extends from the midline onto the chest wall at the
level of the tenth rib for the right side and the eleventh rib for the
left side.
• The pleural cavity is often entered on the right, but not always on
the left.
• The abdominal cavity is not necessarily entered, unless needed.
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47. LAPAROSCOPIC ADRENALECTOMY
Indications :
• Aldosteronoma
• Cushing’s syndrome
Cortisol-producing adenoma
Adrenal hyperplasia from failed treatment of ACTH dependent Cushing’s syndrome
Primary adrenal hyperplasia
• Pheochromocytoma (sporadic or familial)
• Nonfunctioning cortical adenoma (>4–5 cm or atypical radiographic appearance)
Contraindications :
• Any locally invasive adrenal tumor
• Regional lymph node metastases
• Large adrenocortical cancer
• Existing contraindication to laparoscopic surgery
• Prior nephrectomy, splenectomy, liver resection on affected side (relative)
Controversial :
• Suspected primary adrenal malignancy
• Large tumor size
• Adrenal metastasis
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48. •Patient position for the transabdominal
lateral approach to laparoscopic (left)
adrenalectomy
•The table is flexed at the waist and
placed in a reverse Trendelenburg
position.
•Port site placement for laparoscopic left
adrenalectomy using the transabdominal
lateral approach.
•The anterior and posterior axillary lines,
costal margin, and iliac crest are identified
by the dashed lines.
•The ports should be spaced at intervals of
5 cm or greater to allow external freedom
of movement.
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49. Schematic illustration of sequential steps in laparoscopic exposure of the left adrenal
gland (lateral flank approach)
A The splenocolic ligament is divided first (dotted line),
followed by complete division of the splenorenal
ligament (dashed line)
B The spleen is rotated medially, and the kidney is retracted
laterally. The vein is ligated at the inferomedial border of the
adrenal with endoscopic clips
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50. •Laparoscopic exposure
and ligation of the left
adrenal vein.
•A right angle dissector is
elevating the left adrenal
vein.
•The adrenal gland is
indicated by the small
arrowheads.
•Note the inferior phrenic
vein (larger arrowheads)
entering the left adrenal
vein proximal to the latter’s
entry into the renal vein.
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51. Schematic representation of anatomic relationships as viewed during laparoscopic
right adrenalectomy with the transabdominal lateral flank approach
A The right triangular ligament of the liver is divided to
allow full medial rotation of the right lobe of the liver
B The medial border of the adrenal has been partially
dissected free to expose the inferior vena cava and right
adrenal vein
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52. •Laparoscopic retroperitoneal
approach may be carried out with
the patient in either a semi-
jackknife or lateral position.
•The dissection is performed with
a balloon dissector + 2 additional
trocars.
•The advantages of the
retroperitoneal approach are that
the peritoneal cavity does not
need to be entered, which may be
especially important in the patient
with extensive prior upper
abdominal surgery.
•However, this approach is
generally more difficult and has a
smaller working space, and the
orientation can be difficult.
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53. Cortex-sparing adrenalectomy
• It is a subtotal adrenalectomy and not medullary extirpation.
• Either open or laparoscopic for cushing’s disease and adrenal neoplasms.
• Intraoperative U/S should be used.
• Avoid hormone replacement in bilaterality
• Preserves adrenal tissue in unilateral tumors for unexpected future events.
• At least 1/3 of one gland is preserved in non-invasive tumors.
• Waiting for long term results concerning its safety and effectiveness .
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54. • The adrenal gland is a common site for
metastases.
• 1% to 30% of adrenal incidentaloma are
metastases.
• An adrenal mass in a patient with a known prior or concurrentextraadrenal malignancy
is an adrenal metastasis until proven otherwise.
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55. Cancers that frequently metastasize to the adrenal
include :
• Breast
• Lung
• Renal cell carcinoma
• Melanoma
• Lymphoma
Adrenalectomy may be indicated in patients with
solitary adrenal metastasis who have no evidence of
metastatic disease elsewhere + Controlled 1ry.
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56. Diagnosis
• An accurate patient history is crucial in evaluating these masses
(malignancy?).
• CT scan :
Tumor size > 4 cm
Irregular borders
Inhomogeneous appearance MALIGNANT???
Local invasion,
Lymphadenopathy
Necrosis
• Determining the Hounsfield units (HU) of the tumor in a noncontrasted CT
> 10 to 20 HU  MALIGNANT???
• MRI  Benign adenomas typically have rapid washout of gadolinium
contrast due to their high lipid content, whereas malignant lesions have
prolonged retention of contrast.
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57. A patient who had liver transplantation for a hepatoma then subsequently developed a left adrenal mass.
Nonenhanced computed tomography of a left metastatic adrenal tumor, 16 cm in greatest dimension.
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58. PET scan
• Delineate a metabolically active metastasis
from a benign cortical adenoma.
• Superior to total-body CT scanning in
demonstrating evidence of other sites of
metastases.
Fine-needle aspiration biopsy (FNA) under CT or
ultrasound guidance
• Done only if the results of biopsy will alter
therapy.
• Excluded pheochromocytoma first.
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59. • The unexpected discovery of adrenal tumors on
diagnostic imaging studies for nonadrenal clinical
disorders is known as adrenal incidentalomas.
• Found in 1% to 4% of individuals undergoing
abdominal imaging studies.
• Less than 1% of patients younger than 30 years
but in 7% of patients older than 70 years.
• No sex predominance of adrenal incidentalomas.
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60. Differential Diagnosis
• Primary Adrenal Neoplasm
Nonfunctioning
Cortical adenoma/carcinoma
Cyst
Myelolipoma
Ganglioneuroma
Hemorrhage/hematoma
Functioning
Cortical adenoma/carcinoma: hypercortisolism, hyperaldosteronism
Pheochromocytoma
• Metastasis
Lung
Kidney
Breast
Gastrointestinal
Melanoma
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61. Computed tomography scan demonstrates a right
complex adrenal cyst
Characteristic fat density of a large left adrenal
myelolipoma on magnetic resonance imaging
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62. Biochemical Testing for Adrenal Incidentalomas
• Hypercortisolism Overnight dexamethasone (1 mg)
suppression  Serum cortisol >5 µg/dl
• Pheochromocytoma  Plasma catecholamine and
metanephrine  NE 2000 pg/ml, EPI >200 pg/ml,
MN >0.4 mg/24 hr
• Hyperaldosteronism (patient has hypertension or
hypokalemia)  Plasma aldosterone and renin
activity  Aldosterone >20 ng/dl, aldosterone/renin
ratio >30
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63. Rational approach to patients with adrenal incidentalomas. FNA, Fine needle aspiration
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65. • Neuroblastoma and pheochromocytoma are
the two most important tumors which arise
from the adrenal medulla.
• Both tumors may also arise from extra-adrenal
sites, specifically, in the paraganglia of the
sympathetic chain.
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66. Physiology of the Adrenal Medulla
• Derived from the embryonic neural crest.
• Chromaffin cells store and secrete dopamine, norepinephrine, and
epinephrine (also synthesized in the brain and in sympathetic neurons).
• The synthesis of catecholamines from tyrosine involves the sequential
action of four enzymes:
(1) Tyrosine hydroxylase : tyrosine  L - dihydroxyphenylalanine (dopa)
(2) Aromatic L-amino acid decarboxylase : dopa  dopamine
(3) Dopamine-β-hydroxylase :dopamine  L-norepinephrine
(4) Phenylethanolamine-N-methyltransferase (PNMT) : L-norepinephrine 
L-epinephrine.
• PNMT is localized exclusively in cells of the adrenal medulla and the organ
of Zuckerkandl. Thus, epinephrine-secreting tumors arise only in these two
sites.
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67. • The physiologic responses to catecholamines are
mediated by α- and β-adrenergic receptors on
peripheral tissues.
• α-Adrenergic receptors have highest affinity for
norepinephrine, less for epinephrine, and least for
isoproterenol.
• β-Adrenergic receptors are most responsive to
isoproterenol and least to norepinephrine.
• Specific antagonists recognize each receptor class:
α receptors are antagonized by phentolamine and
phenoxybenzamine, and β receptors are blocked by
propranolol.
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68. • Catecholamines are metabolized in liver and kidney by
two enzymes, monoamine oxidase (MAO) and
catechol-O-methyl transferase (COMT).
• In these tissues, MAO and COMT convert epinephrine
or norepinephrine to methoxyhydroxyphenylglycol
(MHPG), vanillylmandelic acid (VMA),
normetanephrine, and metanephrine.
• These inactive metabolites are renally cleared and are
measurable in the urine either as free compounds or as
conjugates of glucuronide or sulfate.
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69. • Pheochromocytoma is a tumor arising in
chromaffin cells and sustentacular cells of the
adrenal medulla and the extra-adrenal
paraganglia.
• Extra-adrenal pheochromocytomas are also
called functional paragangliomas and may
occur in sympathetic ganglia in the neck,
mediastinum, abdomen, pelvis, and organ of
Zuckerkandl.
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70. • Poll, a pathologist, coined the term, pheo
meaning "dusky" and chromo meaning "color" in
1905.
• The first description of a pheochromocytoma is
credited to Frankel, who reported finding
bilateral adrenal tumors in an 18-year old woman
who died precipitously in 1886.
• Roux and Mayo independently reported the first
successful resections of pheochromocytomas in
1926 and 1927, respectively.
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71. • Rare tumors, occurring in 2 to 8 persons per million.
• Males and females are equally affected.
• Peak age of presentation occurs in the fourth and fifth
decades.
• The rule of “tens” is a commonly cited and fairly accurate
description of pheochromocytomas:
Bilateral in 10%
Extra-adrenal in 10%
Familial in 10%
Malignant in 10%
In children in 10% of cases.
• More frequent in the right gland than in the left.
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72. • Occur in the adrenal medulla in 90% of cases.
• The organ of Zuckerkandl is the most common extra-
adrenal site.
• Extra-adrenal pheochromocytomas generally secrete
norepinephrine but not epinephrine.
• Other hormones such as adrenocorticotropin (ACTH),
neuron-specific enolase, IL6, vasoactive intestinal peptide,
neuropeptide y, PTH-rP, calcitonin, and chromogranin A
may also be secreted  Malignancy??
• Malignancy occurs more commonly in extraadrenal sites,
women, and familial malignant pheochromocytoma.
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73. NO PATHOLOGIC OR CLINICAL CRITERIAACCURATELYPREDICT
MALIGNANCY, EXCEPT:
THE PRESENCE OF LOCOREGIONAL INVASION
OR
METASTATIC DISEASE.
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74. SIGNS AND SYMPTOMS
• Silent incidental adrenal mass.
• Hypertension sustained (50%)
paroxysmal (30%)
absent (20%)
• Headache
• Palpitations
• Pallor
• Anxiety
• Dizziness
• Syncope
• Sweating
• Flushing
• Familial syndrome (MEN II)
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75. • Sudden death has been reported in patients with known or unsuspected
pheochromocytomas (provocative testing, percutaneous biopsy of the tumor,
or surgical procedures for other indications).
• Stroke
• Myocardial infarction
• Cardiac dysrhythmias
• Orthostatic hypotension
• Obstipation
• Ileus
• Megacolon
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76. Biochemical testing
• 24-hour urinary excretion of total or fractionated
metanephrines, catecholamines and VMA.
• Plasma metanephrines (high sensitivity and
specificity).
N.B. :
1-Urinary VMA is the least specific test
2-Extraadrenal pheochromocytomas or
paragangliomas (apart from Zuckerkandl
tumors)do not secrete epinephrine
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77. Imaging
• CT readily detects tumors 1 cm and larger, with a reported
sensitivity of 87% to 100%.
• MRI is similarly sensitive (T2-weighted image brightness three times
greater than liver is highly specific for pheochromocytoma).
• Iodine-131-metaiodobenzylguanidine (131 I-MIBG)  most useful
in localizing extra-adrenal tumors not seen with conventional
imaging and in following patients with malignant
pheochromocytomas.
• PET scanning is particularly useful for pheochromocytomas or
paragangliomas that do not accumulate MIBG.
Ihab Samy 2010

78. T2-weighted MR study of a left-sided pheochromocytoma (black arrow). The gallbladder (white arrow) has an increased signal
intensity because of its high water content.
Pheochromocytomas, adrenocortical carcinomas, and metastatic lesions to the adrenal gland demonstrate this high signal
intensity, possibly because of their high water content.
Ihab Samy 2010

79. A, Coronal magnetic
resonance image of a left
adrenal
pheochromocytoma. Note
the characteristic
brightness of a
pheochromocytoma on the
T2-weighted image.
B, Cross-sectional image of
the same patient with a
left adrenal
pheochromocytoma on
computed tomography.
Ihab Samy 2010

80. PERIOPERATIVE MANAGEMENT
Preoperative:
Aim :
(1) Control of hypertension
(2) α blockade to prevent intraoperative
hypertensive crisis due to tumor manipulation
and release of catecholamines
(3) Fluid resuscitation to prevent circulatory
collapse after removal of the catecholamine-
secreting tumor.
Ihab Samy 2010

81. • Methods:
Phenoxybenzamine (a long-acting nonselective, noncompetitive α-blocker) 1 to 3 weeks
preoperatively.
The dosage may start at 10 mg 2 or 4 times a day orally and may be increased to effect, or until
orthostatic hypotension is encountered.
Prazosin, Doxazosin, or Terazosin (Selective α1-adrenergic blockers) are preferred because they
preserve the α2 (catecholamine reuptake) mechanism and are better tolerated in the outpatient
setting.
ACE inhibitors and calcium channel blockers  second-line agents.
β-blockers should never be started before adequate α blockade, because this may result in unopposed
α stimulation leading to severe hypertension, congestive heart failure, and pulmonary edema.
It is indicated after α blockade if arrhythmias are present.
Propranolol 10 mg 3 times a day may be given.
Metyrosine (tyrosine hydroxylase inhibitor)
Daily administration of 1 to 4 mg may decrease the catecholamine synthesis up to 80% but requires
2 to 3 days to become effective.
It has significant side effects, such as nausea, diarrhea, and extrapyramidal signs in prolonged use.
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82. Intraoperative:
• Experienced anesthesiologist.
• Close central venous and arterial pressure monitoring.
• Careful use of anesthetics (may trigger the release of
catecholamines from pheochromocytomas)  enflurane and
isoflurane have been used successfully
• Use of hemodynamic stabilizing drugs such as nitroprusside,
phentolamine, and esmolol.
• Minimal handling of the tumor
• Early isolation of the adrenal vein  Warn the anesthesiologist 
profoud hypotension (short half-life of catecholamines)
• Avoidance of capsular rupture
Ihab Samy 2010

83. • Postoperative:
• Fluid resuscitation expand intravascular volume.
• Intensive care unit arterial blood pressure and urine
output monitored (first 24 hours after operation).
• Monitoring of the serum glucose concentration
rebound hyperinsulinemia from catecholamine-
induced suppression of insulin secretion.
• Lifelong follow-up The lifetime rate of recurrence or
metastatic development is 6.5% to 15%.
Ihab Samy 2010

84. OPERATIVE COMPLICATIONS
• Bleeding  from the adrenal vein, the IVC, the
liver, or the spleen.
• Injury to the tail of the pancreas (rare) 
pancreatic fistulas and abscesses.
• Pneumothorax (rare).
• Postoperative adrenal insufficiency  bilateral
adrenalectomy for bilateral pheochromocytomas
(MEN II).
Ihab Samy 2010

85. • 10-15% of pheochromocytomas are malignant.
• Bony metastases  External beam radiation.
• Soft tissue metastases  131I-MIBG
• Surgical debulking is indicated when possible.
• Chemotherapy regimens have been disappointing (The Averbuch regimen
1988  CVD).
• Cytotoxic somatostatin analogs  SSR 2&5 while Pheochromocytoma
express SSR3.
• Malignant pheochromocytomas express cyclooxygenase 2 receptors and
high levels of VEGF.
Ihab Samy 2010

86. Management algorithm for unresectable metastatic pheochromocytoma
Ihab Samy 2010

87. Ihab Samy 2010