pheochromocytoma refers to a neural crest tumor arising from the adrenal medulla (90%)
paraganglioma refers to a neural crest tumor arising from extraadrenal sympathetic and
parasympathetic ganglia (10%)
affects men and women equally
peak incidence in sporadic cases is 40 – 50 years of age
affects ~ 0.2% of hypertensive patients
10% are malignant in sporadic cases
40% are associated with inherited syndromes (MEN2, von Hippel-Lindau disease,
neurofibromatosis type 1)
familial cases present at an earlier age and are more likely to be bilateral, extra-adrenal, or malignant
Clinical manifestations
50% of patients are symptomatic and 50% are discovered incidentally on routine imaging
classic clinical triad consists of headache, sweating, and palpitations
other symptoms/signs include hypertension, blurred vision, chest pain, tachycardia,
anxiety
Diagnosis
Biochemical Screening
pheochromocytoma is diagnosed by detecting elevated levels of catecholamines in the blood and
urine
24-hour urine collection for catecholamines and fractionated metanephrines is
the most reliable test
plasma fractionated metanephrines is 99% sensitive (true negative),
but only 85% specific (true positive)
a negative blood test essentially rules out pheochromocytoma, but a positive test is
unreliable by itself and must be confirmed by two 24-hour urine collections
many foods and drugs can lead to falsely elevated blood or urine catecholamine or metabolite
levels
equivocal results can be further clarified by the clonidine suppression test, which measures
plasma free normetanephrine levels after the oral administration of clonidine
a positive clonidine suppression test shows nonsuppression of plasma normetanephrine levels
Localization
radiologic localization should follow biological confirmation
15% of tumors are extra-adrenal, but the great majority of these are found in the abdomen and pelvis
most common sites of extra-adrenal tumors are the superior and inferior abdominal paraaortic areas
(75%); urinary bladder (10%); thorax (10%); skull base, neck, and pelvis (5%)
since the average tumor size is ~ 5 cm in size, they are easily detected by CT or MRI
CT Characteristics
increased attenuation on noncontrast CT (>20 Hounsfield units)
increased mass vascularity
delay in contrast medium washout: <50% washout at 10 minutes
cystic and hemorrhagic changes
MRI
high signal intensity on T2-weighted images (other adrenal tumors are isointense)
T1- and T2-Weighted MRI Images
MIBG Scan
very specific for pheochromocytoma
used for detecting extra-adrenal localization or metastatic disease if the CT and MRI are negative
Paraaortic Pheochromocytoma
FNA
shouldn’t be done because of a high rate of complications
Perioperative management
Preoperative Management
Alpha-adrenergic Blockade
phenoxybenzamine or prazosin should be started 7 - 14 days before surgery
dose is titrated upwards until the patient becomes orthostatic
tachycardia and nasal congestion are significant side effects
Beta-adrenergic Blockade
used for persistent tachycardia or arrhythmias
should only be used after alpha blockade has been achieved, because unopposed
vasoconstriction will worsen hypertension
Volume Resuscitation
patients are intravascularly volume depleted secondary to chronic alpha vasoconstriction
preop alpha blockade increases venous capacitance, exacerbating the volume depletion
patients are asked to start a high sodium diet to facilitate volume expansion
Intraoperative Management
must be prepared for dramatic changes in hemodynamics during pheochromocytoma surgery
large-bore IVs are required for rapid volume resuscitation
arterial line is mandatory to monitor blood pressure swings
pulmonary artery catheter may be of value in patients with cardiac dysfunction
ventricular arrhythmias may be managed with intravenous lidocaine and magnesium
Hypertension
usually managed with sodium nitroprusside (Nipride) because of its rapid onset of
action and short duration of action
esmolol, nitroglycerine, and nicardipine can also be used as supplemental agents
Hypotension
may occur after ligation of the adrenal vein
management includes cessation of vasodilators, institution of pressors, rapid volume
expansion of fluid or blood
vasopressin may be used for refractory hypotension
Surgical management
Operative Approach
most pheochromocytomas can excised from a laparoscopic lateral transabdominale approach
open surgery is indicated for large tumors, or if local invasion or vascular invasion
is present
Port Placement - Laparoscopic Right Adrenalectomy
Operative Exposure
Left Adrenal
splenic flexure is mobilized inferiorly
spleen and pancreas are mobilized medially
adrenal vein enters the left renal vein
Right Adrenal
lateral attachments and triangular ligament of the liver are divided, and the right
lobe of the liver is retracted superiorly and medially
hepatic flexure is mobilized inferiorly
duodenum is mobilized off the IVC (Kocher maneuver)
right adrenal vein enters the IVC posterolaterally
Malignant Pheochromocytoma
defined by the development of metastases (liver, lung, bone, lymph nodes)
tumor where paraganglionic tissue is present may represent multifocal disease
recurrent, multifocal, and metastatic disease should be resected if all identified disease can be removed
MIBG-avid tumors can be treated with 131I-MIBG radionuclide therapy
most tumors express somatostatin receptors and can be treated with radiolabeled somstostatin analogues
catecholamine excess can be managed with alpha1 blockers
131I-MIBG Treatment
Incidentaloma
Overview
up to 5% of abdominal imaging studies may detect an incidental adrenal mass
the workup of these masses is focused on determining functional status and the likelihood of malignancy
majority of incidentalomas are nonfunctioning cortical adenomas or other benign lesions (myelolipoma)
that do not require treatment
if the patient has a history of malignancy, then a metastatic lesion is most likely
Assessment of Malignancy Risk
Size
the risk of adrenocortical cancer is very low in incidental lesions < 4 cm in maximum diameter
although the risk of adrenal cancer increases with larger lesions, most incidentalomas > 4 cm are benign
most unilateral adrenal masses > 4 cm should be removed, especially in younger, healthier patients
exceptions can be made for larger lesions with benign imaging characteristics (myelolipomas)
Right Adrenal Myelolipoma
Imaging Features
Noncontrast CT Scan
most adrenal adenomas contain a large amount of intracellular fat and have low attenuation on
noncontrast CT (Hounsfield unit < 10)
adrenal masses with HU < 10 are nearly 100% benign
lesions with HU ≥ 10 are malignant in ~ 1/3 of cases
Delayed Contrast-Enhanced CT Scan
adenomas typically take up contrast quickly but also lose it quickly on delayed images
malignant lesions usually have a slower washout of the contrast
contrast washout > 50% after 10 minutes almost guarantees that the lesion is benign
Biochemical Screening
10% - 15% of incidentalomas turn out to be functional (often subclinical)
hormonal assessment of incidentalomas is mandatory because functional tumors should be resected
Cushing’s Syndrome
start with a 1 mg overnight dexamethasone suppression test (DST)
an elevated morning cortisol level is consistent with ACTH-independent autonomous cortisol production
confirmatory testing requires an ACTH level and 24-hour urinary cortisol level
Pheochromocytoma
a negative plasma free metanephrines test rules out a pheochromocytoma
a positive test will require a 24-hour urine for catecholamines and fractionated metanephrines
Aldosteronoma
evaluation begins with measuring the plasma aldosterone concentration and plasma renin activity
a PAC:PRA > 20 will require confirmation with saline suppression testing
Management
Indications for Adrenalectomy
hormonally active tumor
hormonally inactive tumor + size > 4 cm
hormonally inactive tumor < 4 cm with high-risk imaging features
rapid growth on serial imaging
isolated metastatic tumor
Incidental Pheochromocytoma
Observation
patients who don’t require surgery should be followed with serial imaging
a repeat CT scan at 3 – 6 months and then annually for several years is a reasonable approach
biochemical screening should occur annually for 5 years
lesions that increase in size by 1 cm or that become hormonally active should be excised
Incidental Benign Cortical Adenoma
References
Sabiston, 20th ed., pgs 980 – 993
Cameron, 13th ed., pgs 737 – 741, 750 - 756
UpToDate. Clinical Presentation and Diagnosis of Pheochromocytoma. William F. Young, Jr., MD, MSc.
Aug 31, 2020. Pgs 1 – 32
UpToDate. Treatment of Pheochromocytoma in Adults. William F. Young, Jr., MD, MSc,
Electron Kebebew, MD, FACS. Nov 25, 2019. Pgs 1 – 22
UpToDate. Evaluation and Management of the Adrenal Incidentaloma. William F. Young, Jr., MD, MSc,
Electron Kebebew, MD, FACS. Nov 25, 2019. Pgs 1 – 38
