http://www.kidney-international.
org
Diagnosis and management of pheochromocytoma –
recent advances and current concepts
WM Manger1
1
National Hypertension Association, Inc., New York University Medical Center, New York, New York, USA
Pheochromocytoma is a rare but extremely treacherous
neuroendocrine tumor, usually occurring in the adrenals
but sometimes elsewhere in the abdomen, pelvis, chest,
neck, and head. It causes manifestations by secreting
catecholamines into the circulation. Tragically, up to 50%
of pheochromocytomas are discovered at autopsy, mainly
because this tumor was not considered. Clinicians must think
of pheochromocytoma whenever any manifestations
suggesting hypercatecholaminemia occur. Manifestations
can mimic many other diseases, but manifestations without
sustained or paroxysmal hypertension are rarely due to
pheochromocytoma. However, familial pheochromocytoma,
which comprises about 30% of tumors, may rarely be
asymptomatic and cause no hypertension. Biochemical
testing can almost always establish the presence or absence
of a pheochromocytoma. Tumor localization with magnetic
resonance imaging, computed tomography, or 131I or
123
I-MIBG is nearly always possible. Surgical removal is
usually curative; chemotherapy and radiotherapy are
palliative for malignant pheochromocytoma.
Kidney International (2006) 70, S30–S35. doi:10.1038/sj.ki.5001974
KEYWORDS: familial genetics; biochemical testing; imaging localization
Correspondence: WM Manger, National Hypertension Association, Inc., New
York University Medical Center, New York, New York, USA.
E-mail: nathypertension@aol.com
S30
& 2006 International Society of Nephrology
Think of it! This dictum is key to diagnosing pheochromo-
cytoma. There is no more deceptive and treacherous disease
than this neuroendocrine tumor, as, if not recognized and
treated appropriately, it will almost always cause fatal
cardiovascular or cerebrovascular disease or devastating
complications. This neuroendocrine ‘pharmacologic bomb’
has been correctly termed the ‘great masquerader’ since its
clinical characteristics may mimic a large variety of diseases
and result in an erroneous diagnosis.
An autopsy study at the Mayo Clinic in 1981 revealed that
the diagnosis of pheochromocytoma was not suspected in
75% of their patients with this tumor.1 The exact prevalence
of pheochromocytoma is uncertain, but it may occur in
between 0.1 and 0.2% of individuals with sustained diastolic
hypertension. This seems a reasonable estimate, as two large
autopsy series revealed an incidence of about 0.09% of these
tumors.2,3 A more recent Australian report in 2000 indicated
that pheochromocytomas were discovered in 0.05% of 34 000
autopsies.4 (If only patients with a history of diastolic
hypertension had been autopsied, the incidence of pheo-
chromocytoma certainly would have been greater than
0.09%.)
ORIGIN AND FUNCTION
About 85% of pheochromocytomas arise in chromaffin cells
of the adrenal medulla, whereas 18% may be extra-adrenal,5
arising from paraganglionic chromaffin cells (in association
with sympathetic nerves) in the organ of Zuckerkandl,
urinary bladder (o1%), chest (o2%), neck (o0.1%), and at
the base of the skull; tumors also have occurred in the middle
ear and spermatic cord. Extra-adrenal pheochromocytomas
are more common in children (30%) than adults (15%).
Why extra-adrenal tumors are more frequently malignant
(30–40%) than adrenal pheochromocytomas (10%) is un-
known.6 Metastases may occur in lymph nodes, lung, liver,
and bone but not in brain.
Pheochromocytomas usually secrete norepinephrine and
epinephrine but mainly norepinephrine. Some secrete only
one of these catecholamines and rarely dopamine and/or
dopa. A number of peptides and hormones have been
identified in pheochromocytomas, for example, calcitonin,
serotonin, vasoactive intestinal peptide, adrenocortico-
tropic hormone, neuropeptide Y, atrial natriuretic factor,
growth hormone-releasing factor, somatostatin, parathyroid
Kidney International (2006) 70, S30–S35
WM Manger: Diagnosis and management of pheochromocytoma
hormone-related peptide, and others. Some of these sub-
stances may also be secreted into the circulation and cause
clinical, physiologic, and pharmacologic manifestations.6
FAMILIAL PHEOCHROMOCYTOMA
It is now recognized that between 25 and 30% of pheo-
chromocytomas are due to germline mutations. Coexistence
of pheochromocytoma, medullary thyroid carcinoma
(MTC), and/or c-cell hyperplasia or neoplasia constitutes
multiple endocrine neoplasia type 2a. Pheochromocytoma
coexisting with MTC, mucosal neuromas, thickened corneal
nerves, alimentary-tract ganglioneuromatosis, and often a
marfanoid habitus, but rarely parathyroid disease, constitutes
multiple endocrine neoplasia type 2b. MTC may secrete
calcitonin, serotonin, and prostaglandin; pheochromocytoma
may also secrete these hormones, and rarely vasoactive
intestinal peptide.
Hypercalcitonemia suggests MTC or c-cell hyperplasia,
but hypercalcitonemia may be caused by other conditions,
and occasionally pheochromocytoma. Hypercalcemia may
occur in multiple endocrine neoplasia syndromes but may
result from parathyroid hormone secreted by some pheo-
chromocytomas.6
As von Hippel–Lindau (VHL) disease (hemangioblastoma
of the central nervous system and retinal angioma),
neurofibromatosis type 1, and carotid body tumors may
coexist with pheochromocytoma, hypertension in any of
these conditions should prompt a search for this tumor.
Patients with pheochromocytoma should also be screened for
MTC, von Hippel–Lindau, and hyperparathyroidism. If
familial disease is established, first-degree relatives should
be evaluated for genetic mutations of the RET protooncogene
on chromosome 10 for multiple endocrine neoplasia 2a and
2b, on chromosome 3p for VHL, and on chromosome 17q
for familial neurofibromatosis. Gene mutations of the
succinate dehydrogenase family, the SDHD gene on chromo-
some 11q 7 and the SDHB gene on chromosome 1p,8 may
account for 12% of pheochromocytomas and head and neck
paragangliomas.9,10 These mutations predispose to pheo-
chromocytomas as well as neck and head paragangliomas.
Tumors with the SDHD mutation are usually benign, whereas
SDHB mutation carriers have an increased risk of malig-
nancy.
Pheochromocytoma occurs in 14% of patients with VHL.
Common pathological lesions associated with this genetic
disease include renal and pancreatic cysts, cystadenoma of the
epididymis, and renal cell carcinoma.11,12 It is noteworthy
that defects in the VHL gene appear responsible for 60%
of sporadic clear-cell renal carcinomas, the major portion of
all renal-cell carcinomas.13 Very rarely, VHL may coexist
with MTC, carcinoid, pituitary adenoma, neuroblastomas,
angiomas, and cysts elsewhere.11
CLINICAL PRESENTATION
Sustained, labile, or paroxysmal hypertension is almost
always present due to increased circulating catecholamines.
Kidney International (2006) 70, S30–S35
Of great diagnostic importance is the occurrence of
hypertension simultaneously with manifestations suggesting
hypercatecholaminemia, as episodic manifestations without
hypertension are highly atypical. However, normotension
may be present in some individuals with familial pheo-
chromocytoma; furthermore, a few patients with pheochro-
mocytomas that secreted only dopamine and did not cause
hypertension have been reported.
Episodes of hypertension with clinical manifestations of
hypercatecholaminemia usually occur weekly, but may occur
several times daily or only every few months; 80% last less
than 1 h but rarely they last for several days. Attacks may be
precipitated by palpation of the tumor, postural changes,
exertion, anxiety, trauma, pain, ingestion of foods or
beverages containing tyramine (certain cheeses, beers, and
wines), use of certain drugs (histamine, glucagon, tyramine,
phenothiazines, metoclopramide, adrenocorticotropic hor-
mone), intubation, anesthesia induction, chemotherapy, and
micturition or bladder distension (with bladder tumors).6
Manifestations resulting from excess catecholamines
include hypertension (sustained or paroxysmal), frequently
severe hypertensive headaches, generalized inappropriate
sweating, and palpitations (with tachycardia, or occasionally
reflex bradycardia). Additionally, patients may experience
severe anxiety and fear of death, tremulousness, pains in the
chest, abdomen, lumbar area, or groin, nausea, vomiting,
weakness, fatigue, weight loss, warmth or heat intolerance,
dyspnea, hypertension alternating with hypotension, ortho-
static hypotension, parethesias, pallor of the face and upper
body (rarely flushing), and visual impairment (due to
hypertensive retinopathy). Occasionally, seizures occur.
Painless hematuria, frequency, nocturia, and tenesmus may
occur with bladder pheochromocytomas. Severe constipation
or pseudo-obstruction may occur in patients with sustained
hypertension, because catecholamines can inhibit peristalsis;
intense mesenteric artery vasoconstriction due to hyper-
catecholaminemia may cause ischemic intestinal necrosis
with intestinal obstruction. Vasoactive intestinal peptide,
serotonin, or calcitonin, secreted by some pheochromocyto-
mas, may cause diarrhea, sometimes accompanied by
hypokalemia, hypochlorhydria, or achlorhydria.6 Children
may experience polyuria, polydipsia, and convulsions.
Clinical manifestations may result from coexisting endocrine
tumors and VHL.
LABORATORY AND ELECTROCARDIOGRAM ABNORMALITIES
Pheochromocytomas, coexisting endocrine tumors, and VHL
may cause laboratory abnormalities. Hypercatecholaminemia
can cause hyperglycemia and hypertriglyceridemia. Without
diabetes mellitus, hyperglycemia is a common occurrence
and an important clue that suggests pheochromocytoma.
Calcitonin, serotonin, and prostaglandin may be secreted
by MTC and pheochromocytomas, and hypercalcemia may
be caused by increased secretion of parathyroid hormone
from neoplasia or hyperplasia of parathyroid glands, and
rarely from pheochromocytomas.
S31
 WM Manger: Diagnosis and management of pheochromocytoma

Occasionally, a hemanglioblastoma in VHL can secrete
erythropoietin and cause polycythemia. Very rarely, Cush-
ing’s syndrome may result from pheochromocytomas secret-
ing adrenocorticotropic hormone, which increases plasma
cortisol.
Severe catecholamine-induced vasoconstriction can cause
ischemia in multiple organs and result in lactic acidosis and
elevations of pancreatic, hepatic, and cardiac enzymes.
Plasma renin, angiotensin II, and aldosterone may be
elevated from catecholamine stimulation of b1-adrenergic
receptors in the kidney, or, rarely, from compression of a
renal artery by a pheochromocytoma or by a coexisting
neurofibroma.
Electrocardiographic changes resulting from hypercate-
cholaminemia and hypertension include arrhythmias,
changes suggesting myocardial ischemia, damage or left
ventricular strain; their transient appearance during paroxy-
smal hypertension suggests pheochromocytoma in the
absence of other causes. Permanent electrocardiogram
changes can result from prolonged hypertension, myocardial
ischemia, or cardiomyopathy. However, almost any electro-
cardiogram changes can occur but they are not specific for
pheochromocytoma.6
DIAGNOSIS
Perhaps 95% of individuals harboring pheochromocytomas
have sustained or paroxysmal hypertension frequently
associated with headaches, inappropriate generalized
sweating, or palpitations. Asymptomatic patients with hyper-
tension of unknown cause should be screened for pheochro-
mocytoma if they have laboratory or electrocardiogram
abnormalities that may be caused by hypercatecholaminemia,
imaging evidence suggesting this tumor, or diseases some-
times coexisting with pheochromocytoma.
Plasma and 24-h urine metanephrine and normetanephr-
ine are more sensitive than other biochemical tests for
making the diagnosis of sporadic and familial pheochromo-
cytoma (Table 1).14,15 Assays of plasma metanephrine and
normetanephrine or catecholamines drawn from an indwel-
ling catheter in patients recumbent for 30–60 min usually
Table 1 | Sensitivity and specificity of biochemical tests
for diagnosing pheochromocytoma
Sensitivity Specificity
Hereditary Sporadic Hereditary Sporadic
(%) (%) (%)
Plasma
Free metanephrines 98 99 96
Catecholamines 68 92 89
Urine
Fractionated metanephrines 97 99 82
Catecholamines 76 90 96
Total metanephrines 60 88 97
Vanillylmandelic acid 43 76 99
From Manger and Eisenhofer.14
differentiate neurogenic from pheochromocytic hyperten-
sion. Rarely a clonidine suppression test may be indicated to
differentiate these types of hypertension; suppression of
plasma normetanephrine to more than 40% or to normal
levels excludes pheochromocytoma in about 96% of cases.16
A glucagon stimulation test is almost never needed.
Certain drugs, for example, isoproterenol, methyldopa,
levodopa, catecholamines, tricyclic antidepressants, sym-
pathomimetics, and phenoxybenzamine, may cause actual
or spurious plasma catecholamine elevations. As phenoxy-
benzamine is frequently used specifically to control blood
pressure in patients with pheochromocytoma, biochemical
testing should be performed before using this drug. Labetalol
or acetaminophen may interfere with plasma and urine
catecholamines or their metabolites. Monoamine oxidase
inhibitors can elevate urine and plasma metanephrines and
decrease vanillylmandelic acid concentrations.
b-Adrenergic blockers can increase plasma metanephrine,
calcium channel blockers can increase plasma norepinephr-
ine; a-adrenergic blockers can elevate urine norepinephrine;
and buspirone can cause falsely elevated urine metanephrine.
If possible, all of these drugs should be discontinued at least 1
week before biochemical testing. Sudden cessation of
clonidine may elevate plasma and urine catecholamines and
their metabolites, whereas metyrosine decreases catechol-
amine synthesis and may reduce urine catecholamines and
their metabolites. Radio-opaque media with methylgluc-
amine can obscure elevations of total metanephrines.
It must also be appreciated that some stressful conditions
(e.g., strenuous exercise, myocardial infarction, congestive
heart failure, hypoglycemia, hypotension, increased intra-
cranial pressure, hypoxia, acidosis, surgery, trauma), and
some illicit nonprescription and prescription drugs may
activate the adrenergic system and increase catecholamine
secretion.
DIFFERENTIAL DIAGNOSIS
Most of the conditions which may mimic pheochromocyto-
ma are listed in Table 2 and these have been discussed in
detail elsewhere.6,17 Many of these conditions can be excluded
clinically, but it is important to recognize that some of these
conditions and many types of stress may elevate plasma and
urine catecholamines and their metabolites; however, few
conditions increase concentrations to levels occurring with
pheochromocytoma.
Resistance to antihypertensive medications or paroxysmal
(%)
blood pressure increases during treatment with b-blockers, or
marked pressure increases by conditions known to precipitate
attacks (mentioned earlier), should suggest pheochromo-
82
72 cytoma. It is important to recall that recurrent severe
headaches, especially if accompanied by hypertension, may
be caused by pheochromocytomas; too often severe head-
45
aches are ascribed to migraine without considering pheo-
75
89 chromocytoma as a possible cause. It is crucial to consider
86 pheochromocytoma as a cause of hypertension developing
during pregnancy, as, if unrecognized, it carries a high risk of

S32 Kidney International (2006) 70, S30–S35

WM Manger: Diagnosis and management of pheochromocytoma

Table 2 | Conditions that may suggest pheochromocytoma Table 3 | Always consider pheochromocytoma in patients
1. Anxiety, panic attacks with labile blood pressure with
2. Migraine Hypertension of unknown cause
3. Paroxysmal atrial tachycardia Any manifestations of hypercatecholaminemia
4. Hyperdynamic b-adrenergic circulatory state Resistance to antihypertensives
5. Preeclampsia (eclampsia with convulsions) Paroxysmal BP m during b-blocker Rx
6. Unexplained shock BP m caused by conditions that precipitate attacks
7. Unexplained multi-system organ failure and lactic acidosis Severe headaches with BP m (may erroneously suggest migraine)
8. Cardiomyopathy (with failure) Hyperglycemia without known diabetes
9. Baroreflex failure Unexplained cardiomyopathy
10. Familial dysautonomia (Riley–Day syndrome) Neurofibromatosis and hypertension
11. Carcinoid Syndromic (familial) pheochromocytoma
12. Neuroblastoma Postural hypotension (in the absence of antihypertensive Rx)
13. Drug-induced hypertension
14. Factitiously-produced hypertension
15. Cushing’s syndrome
16. Postural tachycardia syndrome (POTS) mas.6,21,22 CT artefacts caused by surgical clips are not
17. Acute infectious disease encountered with MRI, and contrast agents, which are
18. Autonomic hyperreflexia
19. Hyperthyroidism necessary for optimal visualization with CT, are not required
20. Menopause for MRI. Furthermore, contrast media used with CT may
21. Hyperglycemia without Diabetes Mellitus cause allergic reactions, which are almost never caused by
22. Acrodynia (‘Pink Disease’ – mercury poisoning)
gadolinium media (given i.v.), often used with MRI. MRI is
23. Cerebral vasculitis
superior to CT in detecting extra-adrenal, abdominal, pelvic,
Plasma and urine catecholamines and their metabolites may be elevated in
conditions italicized. some cardiac,20,23 and familial pheochromocytomas.6 Liver
metastases are best detected by CT or MRI. Because no
radiation is involved with MRI, it is ideal for imaging
maternal and fetal mortality. Rare presentations, especially pregnant patients and children suspected of harboring a
important to recognize, are unexplained shock that may be pheochromocytoma.
accompanied by abdominal pain, pulmonary edema, and Uptake of 131I-metaiodobenzylguanidine (MIBG) occurs
pronounced mydriasis.18 Rarely, hemorrhagic necrosis in a in up to 85% of pheochromocytomas, and is highly specific
pheochromocytoma presents as an acute abdomen.6 Another (95–100%).24,25 123I-MIBG also possesses this specificity and
rare presentation is multi-system organ failure accompanied it can detect about 90% of tumors. MIBG scintigraphy may
by severe hypertension or hypotension, encephalopathy, be very helpful in detecting adrenal medullary hyperplasia,
hyperpyrexia, and lactic acidosis, that is, pheochromocytoma small and extra-adrenal pheochromocytomas, and meta-
multi-system crisis.19 stases, because it scans the entire body. MIBG uptake may
Finally, it is extremely important to appreciate that occur in neuroblastomas, MTC, carcinoids, and small-cell
congestive heart failure may be caused by catecholamine cardio- lung cancers. As MIBG uptake may be inhibited by labetalol,
myopathy; appropriate treatment may markedly improve reserpine, calcium channel blockers, tricyclic antidepressants,
or restore cardiac function to normal.6 sympathomimetics, cocaine, adrenergic neuron blockers, and
Table 3 lists findings that can be helpful clues which some tranquilizers, these drugs should be discontinued 1
suggest the presence of a pheochromocytoma. week before scintigraphy.6 Bone scanning with (TC)99m may
occasionally demonstrate metastatic lesions missed by MIBG.
111
IMAGING STUDIES Indium octreotide is another radiopharmaceutical agent
Usually, imaging studies are only justified after biochemical taken up by some pheochromocytomas with somatostatin
tests establish the presence of a pheochromocytoma; how- receptors, but it only detects 25% of tumors, but occasionally
ever, some familial tumors may rarely be identified by it may detect metastases missed by 131I MIBG.26
imaging before significant amounts of catecholamines are More recently, 6-[18F]-fluorodopamine ([18F]DA) posi-
secreted. Computed tomography (CT) can identify 95% of tron emission tomography scan was reported superior to
131
adrenal pheochromocytomas 1 cm or larger, and it can I-MIBG scintigraphy in locating metastatic pheochromo-
localize 90% of extra-adrenal abdominal and pelvic tumors cytomas.27 [18F]DA requires less radiation than radioactive
larger than 2 cm. It can also detect chest tumors, although MIBG, there are no adverse thyroid effects, imaging
intrapericardial pheochromocytomas may be missed.20 can be performed immediately, and images are superior
CT requires intravenous and oral contrast for optimal to those using 131I-MIBG. Currently [18F]DA is only available
visualization. at the National Institutes of Health, and further experience is
Magnetic resonance imaging (MRI) is more reliable and needed to determine whether other tumors may take up
more specific than CT in detecting pheochromocytomas, and this agent and what drugs may interfere with its uptake.27,28
signal intensity on T2-weighted images can be fairly If MRI and CT fail to demonstrate pheochromocytomas
characteristic for pheochromocytomas; only rarely will other in the abdomen and pelvis, MRI of the chest and neck is
benign or malignant tumors resemble pheochromocyto- recommended. When available, whole-body MIBG scan

Kidney International (2006) 70, S30–S35 S33


should be performed to help establish that a tumor is a
pheochromocytoma and to detect any metastases before
operation.
Incidentalomas (incidentally recognized adrenal masses)
are encountered in 3–4% of patients undergoing abdominal
CT scan. Furthermore, one large survey indicated that 4.2%
of incidentalomas are pheochromocytomas.29 Although MRI
and MIBG may strongly suggest pheochromocytoma,
demonstration of significantly elevated plasma and urinary
catecholamines or their metabolites is essential to establish
the diagnosis.
If efforts fail to localize a pheochromocytoma, sampling
blood from various sites in the vena cava may permit
localization.
TREATMENT
Preoperative, operative, and postoperative management of
benign and malignant pheochromocytoma are discussed in
detail elsewhere.6,14 With improved imaging techniques,
laparoscopic removal of adrenal and some extra-adrenal
pheochromocytomas is usually performed. Open transperi-
toneal surgical exploration of the abdomen is indicated when
tumors are multiple, very large, or difficult to remove
laparoscopically. Generally, pheochromocytomas should be
removed expeditiously. Familial pheochromocytoma always
must be considered, and patients should be evaluated for
MTC, c-cell hyperplasia, hyperparathyroidism, VHL, and for
succinate dehydrogenase mutations, especially if carotid body
tumors and pheochromocytomas coexist. Evidence of
familial disease requires that first-degree relatives be eval-
uated genetically for pheochromocytoma and coexisting
disease.
Pheochromocytoma in the bladder, chest, or neck requires
special surgical procedures; during pregnancy, tumors should
be removed promptly, but if pregnancy is carried to term to
permit fetal maturity, cesarean section is advisable to avoid
the stress of labor and vaginal delivery.
In the presence of malignant pheochromocytomas with
metastases, it is desirable to resect as much tumor tissue as
possible to reduce the amount of catecholamines entering the
circulation. Radiotherapy with 131I-MIBG may reduce tumor
size and catecholamine secretion. I.v. chemotherapy with
cyclophosphamide, vincristine, and dacarbazine is usually
reserved to treat aggressive metastatic tumors, particularly if
they are symptomatic and causing pain or pressure on vital
structures. Treatment with a combination of 131I-MIBG and
chemotherapy may provide greater therapeutic benefit than
either alone.30 X-ray radiation may be helpful in treating bone
metastases. a and b-Blockers may control hypertension and
symptomatology for many years, and metyrosine can markedly
inhibit catecholamine synthesis and reduce symptoms. Beta
blockers and metyrosine may prevent or minimize catechola-
mine cardiomyopathy.6 Occasionally, patients with metastatic
pheochromocytoma develop a hypersecretory disorder (due to
vasoactive intestinal peptide secretion), with severe diarrhea
that may be benefited by somatostatin (given i.v.).
S34
WM Manger: Diagnosis and management of pheochromocytoma
Alternatives to surgical resection, radiopharmaceutical
therapy, chemotherapy, and radiotherapy include external
beam radiation, cryoablation, radiofrequency ablation, and
transcatheter embolization of hepatic metastases.31,32
SUMMARY AND CONCLUSION
The diagnosis of pheochromocytoma continues to be missed
too frequently; tragically this usually causes death of
individuals harboring this treacherous and deceptive neu-
roendocrine tumor.
The importance of considering this tumor as the cause of
paroxysmal or sustained diastolic hypertension and manifest-
ations of hypercatecholaminemia must be recalled especially
since the diagnosis can almost always be established or
excluded by determining plasma and urine metanephrine and
normetanephrine.
It is probable that this tumor accounts for 0.1–0.2% of
diastolic hypertension in adult Americans. It is noteworthy
that up to 30% of pheochromocytomas are familial;
establishing familial disease requires that first-degree relatives
be genetically screened.
Advances in imaging techniques have markedly improved
the ability to localize pheochromocytomas; radiopharma-
ceutical and positron emission tomography scans aid in
establishing the location and identity of a tumor and the
presence of metastatic lesions.
Today pheochromocytomas of the abdomen can usually
be removed laparoscopically. Tumors of the bladder, chest,
neck, and head require special surgical techniques. Of current
interest are efforts to advance knowledge of the molecular,
genetic, and proteomic characteristics of pheochromocyto-
mas. Why about 90% of these tumors are benign, whereas
10% are malignant remains an enigma that requires
deciphering.
REFERENCES
1. Sutton M, Sheps SG, Lie JL. Prevalence of clinically unsuspected
pheochromocytoma: review of a 50-year autopsy series. Mayo Clin Proc
1981; 56: 354–360.
2. Minno AM, Bennett WA, Kvale WF. Pheochromocytoma. A study of 15
cases diagnosed at autopsy. N Engl J Med 1954; 251: 959–965.
3. von Schlegel GG. Neurofibromatose recklinghausen und
phäochromocytom. Schweiz Med Wochenschr 1960; 90: 31–39.
4. McNeil AR, Blok BH, Koelmeyer TD et al. Pheochromocytomas discovered
during coronal autopsies in Sydney, Melbourne and Auckland. Aust NZJ
Med 2000; 30: 648–652.
5. Whalen RK, Althausen AF, Daniels GH. Extra-adrenal pheochromocytoma.
J Urol 1992; 147: 1–10.
6. Manger WM, Gifford Jr RW. Clinical and Experimental Pheochromocytoma.
Blackwell Science: Cambridge MA, 1996.
7. Baysal BE, Ferrell RE, Willett-Brozick JE et al. Mutations in SDHD, a
mitochondrial complex II gene, in hereditary paraganglioma. Science
2000; 287: 848–851.
8. Astuti D, Latif F, Dallod A et al. Gene mutations in the succinate
dehydrogenase subunit SDHB cause susceptibility to familial
pheochromocytoma and to familial paraganglioma. Am J Hum Genet
2001; 69: 49–54.
9. Pacak K, Lineham WM, Eisenhofer G et al. Recent advances in genetics,
diagnosis, localization, and treatment of pheochromocytoma. Ann Intern
Med 2001; 135: 315–329.
10. Neumann HP, Bausch B, McWhinney SR et al. Germ-line mutations in
nonsyndromic pheochromocytoma. N Engl J Med 2002; 346: 1459–1466.
Kidney International (2006) 70, S30–S35
WM Manger: Diagnosis and management of pheochromocytoma
11. Neuman HPH, Denkel E, Brambs H et al. Pancreatic lesions in the Von
Hippel–Lindau syndrome. Gastroenterology 1991; 101: 465–471.
12. Cohen HT, McGovern FJ. Renal-cell carcinoma. N Engl J Med 2005; 353:
2477–2490.
13. Kim WY, Kaelin WG. Role of VHL gene mutation in human cancer. J Clin
Oncol 2004; 22: 4991–5004.
14. Manger WM, Eisenhofer G. Pheochromocytoma: diagnosis and
management update. Curr Hypert Rep 2004; 6: 477–484.
15. Lenders JWM, Pacak K, Walther MM et al. Biochemical diagnosis
of pheochromocytoma: which test is best? JAMA 2002; 287:
1427–1434.
16. Eisenhofer G, Goldstein DS, Walther MM. Biochemical diagnosis of
pheochromocytoma: how to distinguish true from false-positive test
results. J Clin Endocrinol Metab 2003; 88: 2656–2666.
17. Manger WM. An overview of pheochromocytoma: historical – current
concepts – vagaries and diagnostic challenges. N Y Acad Sci 2006; 1073:
1–20.
18. Bergland BE. Pheochromocytoma presenting as shock. Am J Emerg Med
1989; 7: 44–48.
19. Newell KA, Prinz RA, Pickleman J et al. Pheochromocytoma multisystem
crisis: a surgical emergency. Arch Surg 1988; 123: 956–959.
20. Jebara VA, Uva MS, Farge A et al. Cardiac pheochromocytomas. Ann
Thorac Surg 1992; 53: 356–361.
21. Fink IJ, Reinig JW, Dwyer AJ et al. MR imaging of pheochromocytomas.
J Comput Assist Tomogr 1985; 9: 454–458.
22. Baker EM, Spritzer C, Blinder R et al. Benign adrenal lesions mimicking
malignancy on MR imaging: report of two cases. Radiology 1987; 163:
669–671.
Kidney International (2006) 70, S30–S35
23. Stowers SA, Gilmore P, Sterling M et al. Cardiac pheochromocytoma
involving the left main coronary artery presenting with exertional angina.
Am Heart J 1987; 114: 423–427.
24. Sisson JC, Frager MS, Valk TW et al. Scintigraphic localization of
pheochromocytoma. N Engl J Med 1981; 305: 12–17.
25. Jalil ND, Pattou FN, Combemale F et al. Effectiveness and limits of
preoperative imaging studies for the localizations of pheochromocytomas
and paragangliomas: a review of 282 cases. Eur J Surg 1998; 164: 23–28.
26. van der Harst E, de Herder WW, Bruining HA et al. [123I]-metaiodoben-
zylguanidine and [111In]-octreotide uptake in benign and malignant
pheochromocytomas. J Clin Endocrinol Metab 2001; 86: 685–693.
27. Illias I, Yu J, Carrasquillo JA et al. Superiority of 6-[18F]-fluorodopamine
positron emission tomography versus [131I]-metaiodobenzylguanidine
scintigraphy in the localization of metastatic pheochromocytoma. J Clin
Endocrinol Metab 2003; 88: 4083–4087.
28. Manger WM. Editorial: In search of pheochromocytomas. J Clin Endocrinol
Metab 2003; 88: 4080–4082.
29. Mantero F, Massimo T, Arnoldi G et al. A survey on adrenal incidentaloma
in Italy. J Clin Endocrinol Metab 2000; 85: 637–644.
30. Sisson JC, Shapiro B, Shulkin BL et al. Treatment of malignant
pheochromocytomas with 131I-metaiodobenzylguanidine and che-
motherapy. Am J Clin Oncol 1999; 22: 364–370.
31. Takahashi K, Ashizawa N, Minami T et al. Malignant pheochromocytoma
with multiple hepatic metastases treated by chemotherapy and
transcatheter arterial embolization. Intern Med 1999; 38: 349–354.
32. Pacak K, Fojo T, Golstein DS et al. Radiofrequency ablation: a novel
approach for treatment of metastatic pheochromocytoma. J Natl Cancer
Inst 2001; 93: 648–649.
S35