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Drugs & Diseases > Endocrinology

PHEOCHROMOCYTOMA

Updated: Apr 26, 2024
* Author: Michael A Blake, MBBCh, MRCPI, FRCR; Chief Editor: George T Griffing,
MD more...

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Sections
Pheochromocytoma

* Sections Pheochromocytoma
* Overview

* Practice Essentials
* Pathophysiology
* Etiology
* Epidemiology
* Prognosis
* Show All
* Presentation

* History
* Physical Examination
* Show All
* DDx
* Workup

* Approach Considerations
* Metanephrine and Catecholamine Testing
* Additional Laboratory Tests
* CT Scanning
* MRI and MR Spectroscopy
* Scintigraphy
* Testing for Genetic Disorders
* Histologic Findings
* Show All
* Treatment

* Approach Considerations
* Laparoscopic Adrenalectomy
* Pheochromocytoma in Pregnancy
* Medical Care
* Show All
* Guidelines
* Medication

* Medication Summary
* Alpha Blockers, Antihypertensives
* BPH, Alpha Blocker
* Vasodilators
* Beta Blockers, Nonselective
* Beta Blockers, Beta1 Selective
* Antihypertensives, Other
* Radiopharmaceuticals
* Show All
* Questions & Answers
* Media Gallery
* References

Overview

PRACTICE ESSENTIALS

A pheochromocytoma (see the image below) is a rare, catecholamine-secreting
tumor derived from chromaffin cells. The term pheochromocytoma (in Greek, phios
means dusky, chroma means color, and cytoma means tumor) refers to the color the
tumor cells acquire when stained with chromium salts.

Axial, T2-weighted magnetic resonance imaging (MRI) scan showing large left
suprarenal mass of high signal intensity on a T2-weighted image. The mass is a
pheochromocytoma.
View Media Gallery

About 30% of pheochromocytomas occur as part of hereditary syndromes. Although
pheochromocytomas have classically been associated with 3 syndromes—von
Hippel-Lindau (VHL) syndrome, multiple endocrine neoplasia type 2 (MEN 2), and
neurofibromatosis type 1 (NF1)—there are now 10 genes that have been identified
as sites of mutations leading to these tumors. These different genes produce
pheochromocytomas with different ages of onset, secretory profiles, locations,
and potential for malignancy. [1]

Because of excessive catecholamine secretion, pheochromocytomas may precipitate
life-threatening hypertension or cardiac arrhythmias. [6] If the diagnosis of a
pheochromocytoma is overlooked, the consequences can be disastrous, even fatal;
however, if a pheochromocytoma is found, it is potentially curable. (See
Pathophysiology, Prognosis, and Treatment.) [2]

About 85% of pheochromocytomas are located within the adrenal glands, and 98%
are within the abdomen. When such tumors arise outside of the adrenal gland,
they are termed extra-adrenal pheochromocytomas, or paragangliomas.

Extra-adrenal pheochromocytomas develop in the paraganglion chromaffin tissue of
the nervous system. They may occur anywhere from the base of the brain to the
urinary bladder. Common locations for extra-adrenal pheochromocytomas include
the organ of Zuckerkandl (close to the origin of the inferior mesenteric
artery), bladder wall, heart, mediastinum, and carotid and glomus jugulare
bodies. (See Workup.)

MALIGNANCY

Approximately 10% of pheochromocytomas and 35% of extra-adrenal
pheochromocytomas are malignant. Only the presence of metastases defines
malignancy. However, specific histologic features help to differentiate adrenal
pheochromocytomas with a potential for biologically aggressive behavior from
those that behave in a benign fashion. Among the features that suggest a
malignant course are large tumor size and an abnormal DNA ploidy pattern
(aneuploidy, tetraploidy). [3] Common metastatic sites include bone, liver, and
lymph nodes.

For discussion of pheochromocytoma in children, see the Medscape Drugs &
Diseases article Pediatric Pheochromocytoma. [4]

SIGNS AND SYMPTOMS OF PHEOCHROMOCYTOMA

Classically, pheochromocytoma manifests as spells with the following 4
characteristics:

* Headaches

* Palpitations

* Diaphoresis

* Severe hypertension

Typical patterns of the spells are as follows:

* Frequency may vary from monthly to several times per day

* Duration may vary from seconds to hours

* Over time, spells tend to occur more frequently and become more severe as the
tumor grows

The following may also occur during spells:

* Tremor

* Nausea

* Weakness

* Anxiety, sense of doom

* Epigastric pain

* Flank pain

* Constipation

Clinical signs associated with pheochromocytomas include the following:

* Hypertension: Paroxysmal in 50% of cases

* Postural hypotension: From volume contraction

* Hypertensive retinopathy

* Weight loss

* Pallor

* Fever

* Tremor

* Neurofibromas

* Tachyarrhythmias

* Pulmonary edema

* Cardiomyopathy

* Ileus

* Café au lait spots

See Clinical Presentation for more detail.

DIAGNOSIS OF PHEOCHROMOCYTOMA

Diagnostic tests for pheochromocytoma include the following:

* Plasma metanephrine testing: 96% sensitivity, 85% specificity [2]

* 24-hour urinary collection for catecholamines and metanephrines: 87.5%
sensitivity, 99.7% specificity [5]

Test selection criteria include the following:

* Use plasma metanephrine testing in patients at high risk (ie, those with
predisposing genetic syndromes or a family or personal history of
pheochromocytoma)

* Use 24-hour urinary collection for catecholamines and metanephrines in
patients at lower risk

Imaging studies should be performed only after biochemical studies have
confirmed the diagnosis of pheochromocytoma. Studies are as follows:

* Abdominal CT scanning: Has accuracy of 85-95% for detecting adrenal masses
with a spatial resolution of 1 cm or greater

* MRI: Preferred over CT scanning in children and pregnant or lactating women;
has reported sensitivity of up to 100% in detecting adrenal pheochromocytomas

* Scintigraphy: Reserved for biochemically confirmed cases in which CT scanning
or MRI does not show a tumor

* PET scanning: A promising technique for detection and localization of
pheochromocytomas

Additional studies to rule out a familial syndrome in patients with confirmed
pheochromocytoma include the following:

* Serum intact parathyroid hormone level and a simultaneous serum calcium level
to rule out primary hyperparathyroidism (which occurs in MEN 2A)

* Screening for mutations in the ret proto-oncogene (which give rise to MEN 2A
and 2B) [6]

* Genetic testing for mutations causing the MEN 2A and 2B syndromes

* Consultation with an ophthalmologist to rule out retinal angiomas (VHL
disease)

See Workup for more detail.

MANAGEMENT OF PHEOCHROMOCYTOMA

Surgical resection of the tumor is the treatment of choice and usually cures the
hypertension. Careful preoperative treatment with alpha and beta blockers is
required to control blood pressure and prevent intraoperative hypertensive
crises. [7]

Preoperative medical stabilization is provided as follows:

* Start alpha blockade with phenoxybenzamine 7-10 days preoperatively

* Provide volume expansion with isotonic sodium chloride solution

* Encourage liberal salt intake

* Initiate a beta blocker only after adequate alpha blockade, to avoid
precipitating a hypertensive crisis from unopposed alpha stimulation

* Administer the last doses of oral alpha and beta blockers on the morning of
surgery

See Treatment and Medication for more detail.

Next: Pathophysiology

PATHOPHYSIOLOGY

The clinical manifestations of a pheochromocytoma result from excessive
catecholamine secretion by the tumor. Secretion may occur either intermittently
or continuously. Catecholamines typically secreted are norepinephrine and
epinephrine; some tumors produce dopamine. [8]

The biologic effects of catecholamines are well known. Stimulation of
alpha-adrenergic receptors results in elevated blood pressure, increased cardiac
contractility, glycogenolysis, gluconeogenesis, and intestinal relaxation.
Stimulation of beta-adrenergic receptors results in an increase in heart rate
and contractility. [7]

Catecholamine secretion in pheochromocytomas is not regulated in the same manner
as in healthy adrenal tissue. Unlike the healthy adrenal medulla,
pheochromocytomas are not innervated, and catecholamine release is not
precipitated by neural stimulation. The trigger for catecholamine release is
unclear, but multiple mechanisms have been postulated, including direct
pressure, medications, and changes in tumor blood flow.

Relative catecholamine levels also differ in pheochromocytomas. Most
pheochromocytomas secrete norepinephrine predominantly, whereas secretions from
the normal adrenal medulla are roughly 85% epinephrine.

A retrospective study by Abou Azar et al found a direct correlation between the
size of a pheochromocytoma and its biologic activity, reporting that tumors with
a diameter of 2.3 cm or more result in levels of metanephrine and catecholamine
that are three times the upper limit of normal. The investigators suggested that
“[t]hese findings may allow clinicians to adjust timing of operative
intervention.” [9]

In a study using cardiac magnetic resonance imaging, Ferreira et al found that
patients with pheochromocytoma who underwent curative surgery nonetheless
continued to demonstrate systolic and diastolic strain, focal fibrosis, and T1
abnormalities, with the last possibly indicating the presence of diffuse
fibrosis. According to the investigators, the study’s results suggest more than
just hypertensive heart disease at work and that catecholamine toxicity in
pheochromocytoma may be responsible for long-lasting myocardial changes. [10]

In hereditary forms of pheochromocytoma, the secretory profiles vary according
to the underlying syndrome. Eisenhofer et al found that pheochromocytomas
associated with VHL typically produce norepinephrine only, while those
associated with MEN 2 and NF1 typically produce both epinephrine and
norepinephrine. Tumors in patients with germline mutations of succinate
dehydrogenase subunit genes (SDHB and SDHD), which cause familial paraganglioma,
principally produce dopamine. [11]

PRECIPITANTS OF HYPERTENSIVE CRISIS

Precipitants of a hypertensive crisis include the following:

* Anesthesia induction

* Opiates

* Dopamine antagonists: Eg, metoclopramide [12]

* Cold medications

* Beta blockers [12]

* Drugs that inhibit catecholamine reuptake: Eg, tricyclic antidepressants and
cocaine

* Childbirth

Previous
Next: Pathophysiology

ETIOLOGY

Although the majority of pheochromocytomas are sporadic, approximately 30%
result from inherited mutations. To date, 10 genes associated with
pheochromocytoma and paraganglioma have been identified. [1] Familial syndromes
associated with pheochromocytomas include MEN 2A and 2B, neurofibromatosis (von
Recklinghausen disease), and VHL disease, as well as others.

MEN 2

The MEN 2A and 2B syndromes have been traced to germline mutations in the ret
proto-oncogene on chromosome 10, which encodes a tyrosine kinase receptor
involved in the regulation of cell growth and differentiation. Pheochromocytomas
occur bilaterally in the MEN syndromes in as many as 70% of cases.

MEN 2A

MEN 2A (Sipple syndrome) is characterized by the following:

* Medullary thyroid carcinoma

* Parathyroid adenoma

* Pheochromocytomas

* Hirschsprung disease.

Over 95% of cases of MEN 2A are associated with mutations in the ret
proto-oncogene affecting 1 of 5 codons, located in exon 10 (codons 609, 611,
618, 620) and exon 11 (codon 634).

Clinical diagnosis of MEN 2A requires the occurrence of 2 or more endocrine
tumors in one individual or in close relatives. The risk for medullary thyroid
carcinoma is 95%, the risk for pheochromocytoma is 50%, and the risk for
parathyroid disease is between 20% and 30%. [13]

MEN 2B

MEN 2B is characterized by the following:

* Medullary thyroid carcinoma

* Pheochromocytoma

* Mucosal neurofibromatosis

* Intestinal ganglioneuromatosis

* Hirschsprung disease

* Marfanoid body habitus

Patients with MEN 2B may also have ganglioneuromatosis of the gastrointestinal
(GI) tract, which can cause functional GI problems. A germline missense mutation
in the tyrosine kinase domain of the ret proto-oncogene (exon 16, codon 918) has
been reported to be present in 95% of patients with MEN 2B.

Clinical diagnosis of MEN 2B is based on the presence of mucosal neuromas of the
oral mucosa, enlarged lips with characteristic facial appearance, and marfanoid
habitus. Medullary thyroid carcinoma is virtually assured with MEN 2B, and the
risk of pheochromocytoma is 50%. Parathyroid disease is uncommon with MEN 2B.
[13] Persons diagnosed with MEN 2B should have a prophylactic thyroidectomy in
infancy because of the early and aggressive nature of associated medullary
thyroid carcinoma.

OTHER MUTATIONAL ETIOLOGIES

Novel mutations that cause hereditary pheochromocytoma have been identified in
the MYC-associated factor X (MAX) gene. Loss of MAX function is correlated with
metastatic potential. [14] Burnichon et al concluded that germline mutations in
MAX are responsible for approximately 1% of pheochromocytomas and paragangliomas
in patients without evidence of other known mutations. [15]

A number of other genes, such as the GDNF gene, are associated with development
of adrenal or extra-adrenal pheochromocytomas. The GDNF gene is also associated
with central hypoventilation syndrome and susceptibility to Hirschsprung
disease.

The TMEM127 gene also is associated with susceptibility to pheochromocytoma.
Several families have been described with unique mutations to this gene that
have resulted in the development of pheochromocytoma between young adulthood and
middle age. All of these are inherited in an autosomal dominant fashion with
incomplete penetrance.

VHL DISEASE

VHL disease is associated with the following:

* Pheochromocytoma

* Cerebellar hemangioblastoma

* Renal cell carcinoma

* Renal and pancreatic cysts

* Epididymal cystadenomas

One study found that this syndrome was present in nearly 19% of patients with
pheochromocytomas. [16]

VHL disease is caused by mutations in the VHL gene. [17] This gene encodes a
protein that plays a role in cilia formation, regulation of cellular senescence,
and the oxygen-sensing pathway.

NEUROFIBROMATOSIS AND OTHER DISEASES

Neurofibromatosis, or von Recklinghausen disease, is characterized by congenital
anomalies (often benign tumors) of the skin, nervous system, bones, and
endocrine glands. Only 1% of patients with neurofibromatosis have been found to
have pheochromocytomas, but as many as 5% of patients with pheochromocytomas
have been found to have neurofibromatosis.

Other neuroectodermal disorders associated with pheochromocytomas include
tuberous sclerosis (Bourneville disease, epiloia) and Sturge-Weber syndrome.

Pheochromocytomas may produce calcitonin, opioid peptides, somatostatin,
corticotropin, and vasoactive intestinal peptide. Corticotropin hypersecretion
has caused Cushing syndrome, and vasoactive intestinal peptide overproduction
causes watery diarrhea.

SUCCINATE DEHYDROGENASE COMPLEX

The succinate dehydrogenase complex subunit D protein is encoded by the SDHD
gene, mutations in which cause pheochromocytomas, paragangliomas, and other
tumors. In most tumors, inheritance of the mutation is autosomal dominant with
biallelic expression of the SDHD gene. However, paternal imprinting appears to
be the inheritance pattern in paragangliomas and, in particular, carotid body
tumors resulting from the SDHD gene.

The succinate dehydrogenase complex subunit B protein is encoded by the SDHB
gene. Mutations in this gene are known to cause carotid body tumors and
paragangliomas and are inherited in an autosomal dominant fashion.
Paragangliomas caused by SDHB mutations have a higher rate of malignant
transformation that those that are not.

The succinate dehydrogenase subunit C protein is encoded by the SDHC gene, and
mutations are known to cause paraganglioma. One family with a mutation in this
gene showed maternal inheritance of the condition, [18] but subsequent
investigation has suggested an autosomal dominant inheritance pattern without
evidence of imprinting.

Other succinate dehydrogenase subunit genes with mutations linked to
paraganglioma include SDHA [19] and the newly characterized succinate
dehydrogenase complex assembly factor 2 (SDHAF2) gene. [20] Kunst et al found
phenotypic expression of the SDHAF2 mutation only with paternal inheritance,
which suggests imprinting of the gene. [20]

HEMIHYPERPLASIA

Although its genetics remain incompletely understood, hemihyperplasia (also
called hemihypertrophy) is known to increase tumor risk. The condition may be an
isolated finding or a part of a larger syndrome such as Beckwith-Wiedemann
syndrome, Proteus syndrome, or neurofibromatosis. The tumors most commonly
associated with hemihyperplasia are Wilms tumor and hepatoblastoma, but at least
one patient has been described with isolated hemihyperplasia and an adrenal
pheochromocytoma on the hyperplastic side. [21]

Hemihyperplasia can be caused by paternal uniparental disomy for the 11p15
chromosomal region, as can be seen in isolated hemihyperplasia and
Beckwith-Wiedemann syndrome. Methylation of the LIT1 and H19 genes is important
to the pathogenesis of hemihyperplasia and underscores the importance of
epigenetics in normal growth and in the development of neoplasia.

Previous
Next: Pathophysiology

EPIDEMIOLOGY

Pheochromocytomas are rare, reportedly occurring in 0.05–0.2% of hypertensive
individuals. This accounts for only a portion of cases, however, as patients may
be completely asymptomatic. A retrospective study from the Mayo Clinic revealed
that in 50% of cases of pheochromocytoma, the diagnosis was made at autopsy.
[22] Approximately 10% of pheochromocytomas are discovered incidentally. [23]

A Dutch study, by Berends et al, found an increase in the age-standardized
incidence rate (ASR) of pheochromocytomas and sympathetic paragangliomas in the
Netherlands between 1995 and 2015. The investigators reported that the ASR
between 1995 and 1999 was 0.29 per 100,000 person-years, compared with 0.46 per
100,000 person-years between 2011 and 2015. The ASRs for sympathetic
paragangliomas rose between these same two periods from 0.08 to 0.11 per 100,000
person-years. There was also a trend during this 20-year period towards patients
being older and tumor size smaller at diagnosis. The investigators suggested
that clinical practice changes, along with greater use of imaging and
biochemical studies, were at least partially responsible for the incidence
increases. [24]

RACE- AND AGE-RELATED DEMOGRAPHICS

Pheochromocytomas occur in people of all races, although they are diagnosed less
frequently in the black population. Pheochromocytomas may occur in persons of
any age, but the peak incidence is from the third to the fifth decades of life.
Approximately 10% occur in children. Fifty percent of pheochromocytomas in
children are solitary intra-adrenal lesions, 25% are present bilaterally, and
25% are extra-adrenal.

A study by Iglesias et al looking at 106 patients with pheochromocytoma found
that those diagnosed with the sporadic form of the disease tended to be
significantly older than those with familial pheochromocytoma (54.5 years vs
40.8 years, respectively). [25]

Previous
Next: Pathophysiology

PROGNOSIS

The 5-year survival rate for people with nonmalignant pheochromocytomas is
greater than 95%. In patients with malignant pheochromocytomas, the 5-year
survival rate is less than 50%. [26] Although pheochromocytomas are rare, making
the diagnosis is critical because the malignancy rate is 10%, pheochromocytomas
may be associated with a familial syndrome, they may precipitate
life-threatening hypertension, and the patient may be cured completely with
their removal.

A retrospective study by Dhir et al suggested that among patients with
pheochromocytoma or paraganglioma, the likelihood of malignancy is greater in
persons who are younger, have a larger-sized tumor, or specifically have
paraganglioma, as well as in those patients with germline SDHB mutations. Among
the patients studied, those with malignancy had a median age of 42 years, versus
50 years for patients without malignancy; the median size of malignant versus
nonmalignant tumors was 6.5 cm versus 4 cm, respectively. [27]

Many cardiac manifestations are associated with pheochromocytomas. [28]
Hypertension is the most common complication. Cardiac arrhythmias, such as
atrial and ventricular fibrillation, may occur because of excessive plasma
catecholamine levels. Other complications include the following:

* Myocarditis

* Signs and symptoms of myocardial infarction [29]

* Dilated cardiomyopathy

* Pulmonary edema: Either of cardiac or noncardiac origin

A pheochromocytoma-induced hypertensive crisis may precipitate hypertensive
encephalopathy, which is characterized by altered mental status, focal
neurologic signs and symptoms, or seizures. Other neurologic complications
include stroke from cerebral infarction or an embolic event secondary to a mural
thrombus from dilated cardiomyopathy. Intracerebral hemorrhage also may occur,
because of uncontrolled hypertension.

Pheochromocytoma during pregnancy is extremely rare (0.002% of all pregnancies),
[30] but undiagnosed pheochromocytoma that occurs during pregnancy carries a
grave prognosis, with maternal and fetal mortality rates of 48% and 55%,
respectively. However, maternal mortality is virtually eliminated and the fetal
mortality rate is reduced to 15% if the diagnosis is made antenatally.

A study by Yokomoto-Umakoshi et al demonstrated evidence for the frequent
coexistence of osteoporosis and atherosclerosis in patients with
pheochromocytoma. In the presence of vertebral fracture, patients with
pheochromocytoma had a 58% prevalence of abdominal aortic calcification (AAC),
compared with 6% in pheochromocytoma patients without vertebral fracture.
Moreover, a correlation was found between the degree of catecholamine excess and
the existence of vertebral fracture and AAC. [31]

Clinical Presentation

REFERENCES

1. Därr R, Lenders JWM, Hofbauer LC, Naumann B, Bornstein SR, Eisenhofer G.
Pheochromocytoma: Update on Disease Management. Ther Adv in Endo and Metab.
2012;3(1):11-26. [Full Text].

2. Waguespack SG, Rich T, Grubbs E, Ying AK, Perrier ND, Ayala-Ramirez M, et
al. A current review of the etiology, diagnosis, and treatment of pediatric
pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2010 May.
95(5):2023-37. [QxMD MEDLINE Link].

3. Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to
separate benign from malignant neoplasms: a clinicopathologic and
immunophenotypic study of 100 cases. Am J Surg Pathol. 2002 May.
26(5):551-66. [QxMD MEDLINE Link].

4. Bholah R, Bunchman TE. Review of Pediatric Pheochromocytoma and
Paraganglioma. Front Pediatr. 2017. 5:155. [QxMD MEDLINE Link]. [Full
Text].

5. Sheps SG, Jiang NS, Klee GG, van Heerden JA. Recent developments in the
diagnosis and treatment of pheochromocytoma. Mayo Clin Proc. 1990 Jan.
65(1):88-95. [QxMD MEDLINE Link].

6. Yeterian EH, Pandya DN. Corticothalamic connections of the superior
temporal sulcus in rhesus monkeys. Exp Brain Res. 1991. 83(2):268-84. [QxMD
MEDLINE Link].

7. Elenkova A, Matrozova J, Zacharieva S, Kirilov G, Kalinov K. Adiponectin -
A possible factor in the pathogenesis of carbohydrate metabolism
disturbances in patients with pheochromocytoma. Cytokine. 2010 Jun.
50(3):306-10. [QxMD MEDLINE Link].

8. Eisenhofer G, Pacak K, Huynh TT, Qin N, Bratslavsky G, Linehan WM, et al.
Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma.
Endocr Relat Cancer. 2011 Feb. 18(1):97-111. [QxMD MEDLINE Link].

9. Abou Azar S, Stratton L, Memeh K, et al. Clinical Significance of
Pheochromocytoma Size on the Timing and Extent of Surgery. J Surg Res. 2024
Apr 8. 298:88-93. [QxMD MEDLINE Link].

10. Ferreira VM, Marcelino M, Piechnik SK, et al. Pheochromocytoma Is
Characterized by Catecholamine-Mediated Myocarditis, Focal and Diffuse
Myocardial Fibrosis, and Myocardial Dysfunction. J Am Coll Cardiol. 2016
May 24. 67 (20):2364-74. [QxMD MEDLINE Link]. [Full Text].

11. Eisenhofer G, Lenders JW, Timmers H, Mannelli M, Grebe SK, Hofbauer LC, et
al. Measurements of plasma methoxytyramine, normetanephrine, and
metanephrine as discriminators of different hereditary forms of
pheochromocytoma. Clin Chem. 2011 Mar. 57(3):411-20. [QxMD MEDLINE Link].
[Full Text].

12. Eisenhofer G, Rivers G, Rosas AL, Quezado Z, Manger WM, Pacak K. Adverse
drug reactions in patients with phaeochromocytoma: incidence, prevention
and management. Drug Saf. 2007. 30(11):1031-62. [QxMD MEDLINE Link].

13. Eng C. Seminars in medicine of the Beth Israel Hospital, Boston. The RET
proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung's
disease. N Engl J Med. 1996 Sep 26. 335(13):943-51. [QxMD MEDLINE Link].

14. Comino-Mendez I, Gracia-Aznarez FJ, Schiavi F, Landa I, et al. Exome
sequencing identifies MAX mutations as a cause of hereditary
pheochromocytoma. Nat Genet. 2011 Jun 19. 43(7):663-7. [QxMD MEDLINE Link].

15. Burnichon N, Cascon A, Schiavi F, Morales NP, Comino-Mendez I, et al. MAX
mutations cause hereditary and sporadic pheochromocytoma and paraganglioma.
Clin Cancer Res. 2012 May 15. 18(10):2828-37. [QxMD MEDLINE Link].

16. Neumann HP, Berger DP, Sigmund G, Blum U, Schmidt D, Parmer RJ, et al.
Pheochromocytomas, multiple endocrine neoplasia type 2, and von
Hippel-Lindau disease. N Engl J Med. 1993 Nov 18. 329(21):1531-8. [QxMD
MEDLINE Link].

17. Gergics P, Patocs A, Toth M, Igaz P, Szucs N, Liko I, et al. Germline VHL
gene mutations in Hungarian families with von Hippel-Lindau disease and
patients with apparently sporadic unilateral pheochromocytomas. Eur J
Endocrinol. 2009 Sep. 161(3):495-502. [QxMD MEDLINE Link].

18. Niemann S, Becker-Follmann J, Nurnberg G, Ruschendorf F, Sieweke N, et al.
Assignment of PGL3 to chromosome 1 (q21-q23) in a family with autosomal
dominant non-chromaffin paraganglioma. Am J Med Genet. 2001 Jan 1.
98(1):32-6. [QxMD MEDLINE Link].

19. Burnichon N, Briere JJ, Libe R, Vescovo L, Riviere J, et al. SDHA is a
tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 Aug 1.
19(15):3011-20. [QxMD MEDLINE Link]. [Full Text].

20. Kunst HP, Rutten MH, de Mönnink JP, Hoefsloot LH, Timmers HJ, Marres HA, et
al. SDHAF2 (PGL2-SDH5) and hereditary head and neck paraganglioma. Clin
Cancer Res. 2011 Jan 15. 17(2):247-54. [QxMD MEDLINE Link].

21. van den Akker EL, de Krijger RR, de Herder WW, Drop SL. Congenital
hemihypertrophy and pheochromocytoma, not a coincidental combination?. Eur
J Pediatr. 2002 Mar. 161(3):157-60. [QxMD MEDLINE Link].

22. Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of
pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin
Proc. 1983 Dec. 58(12):802-4. [QxMD MEDLINE Link].

23. Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N
Engl J Med. 2007 Feb 8. 356(6):601-10. [QxMD MEDLINE Link].

24. Berends AMA, Buitenwerf E, de Krijger RR, et al. Incidence of
pheochromocytoma and sympathetic paraganglioma in the Netherlands: A
nationwide study and systematic review. Eur J Intern Med. 2018 Jan 17.
[QxMD MEDLINE Link].

25. Iglesias P, Santacruz E, Garcia-Sancho P, et al. Pheochromocytoma: a
three-decade clinical experience in a multicenter study. Rev Clin Esp. 2020
Jul 6. [QxMD MEDLINE Link].

26. Hamidi O, Young WF Jr, Gruber L, et al. Outcomes of patients with
metastatic phaeochromocytoma and paraganglioma: a systematic review and
meta-analysis. Clin Endocrinol (Oxf). 2017 Jul 26. [QxMD MEDLINE Link].

27. Dhir M, Li W, Hogg ME, et al. Clinical Predictors of Malignancy in Patients
with Pheochromocytoma and Paraganglioma. Ann Surg Oncol. 2017 Sep 7. [QxMD
MEDLINE Link].

28. Parikh PP, Rubio GA, Farra JC, Lew JI. Nationwide review of hormonally
active adrenal tumors highlights high morbidity in pheochromocytoma. J Surg
Res. 2017 Jul. 215:204-10. [QxMD MEDLINE Link].

29. Boulkina LS, Newton CA, Drake AJ 3rd, Tanenberg RJ. Acute myocardial
infarction attributable to adrenergic crises in a patient with
pheochromocytoma and neurofibromatosis 1. Endocr Pract. 2007 May-Jun.
13(3):269-73. [QxMD MEDLINE Link].

30. Lenders JW. Pheochromocytoma and pregnancy: a deceptive connection.Eur J
Endocrinol. 2012 Feb;166(2):143-50. Epub 2011 Sep 2.

31. Yokomoto-Umakoshi M, Umakoshi H, Ogata M, et al. Coexistence of
osteoporosis and atherosclerosis in pheochromocytoma: new insights into its
long-term management. Osteoporos Int. 2020 Jul 2. [QxMD MEDLINE Link].

32. Prejbisz A, Lenders JW, Eisenhofer G, Januszewicz A. Cardiovascular
manifestations of phaeochromocytoma. J Hypertens. 2011 Nov. 29(11):2049-60.
[QxMD MEDLINE Link].

33. La Batide-Alanore A, Chatellier G, Plouin PF. Diabetes as a marker of
pheochromocytoma in hypertensive patients. J Hypertens. 2003 Sep.
21(9):1703-7. [QxMD MEDLINE Link].

34. Gagnon N, Mansour S, Bitton Y, Bourdeau I. TAKOTSUBO-LIKE CARDIOMYOPATHY IN
A LARGE COHORT OF PATIENTS WITH PHEOCHROMOCYTOMA AND PARAGANGLIOMA. Endocr
Pract. 2017 Jul 13. [QxMD MEDLINE Link].

35. [Guideline] Chen H, Sippel RS, O'Dorisio MS, Vinik AI, Lloyd RV, Pacak K.
The North American Neuroendocrine Tumor Society consensus guideline for the
diagnosis and management of neuroendocrine tumors: pheochromocytoma,
paraganglioma, and medullary thyroid cancer. Pancreas. 2010 Aug.
39(6):775-83. [QxMD MEDLINE Link]. [Full Text].

36. Lenders JW, Pacak K, Walther MM, Linehan WM, Mannelli M, Friberg P, et al.
Biochemical diagnosis of pheochromocytoma: which test is best?. JAMA. 2002
Mar 20. 287(11):1427-34. [QxMD MEDLINE Link].

37. de Jong WH, Eisenhofer G, Post WJ, Muskiet FA, de Vries EG, Kema IP.
Dietary influences on plasma and urinary metanephrines: implications for
diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab. 2009
Aug. 94(8):2841-9. [QxMD MEDLINE Link].

38. Jimenez C, Cote G, Arnold A, Gagel RF. Review: Should patients with
apparently sporadic pheochromocytomas or paragangliomas be screened for
hereditary syndromes?. J Clin Endocrinol Metab. 2006 Aug. 91(8):2851-8.
[QxMD MEDLINE Link].

39. Eisenhofer G, Goldstein DS, Walther MM, Friberg P, Lenders JW, Keiser HR,
et al. Biochemical diagnosis of pheochromocytoma: how to distinguish true-
from false-positive test results. J Clin Endocrinol Metab. 2003 Jun.
88(6):2656-66. [QxMD MEDLINE Link].

40. Lenders JW, Pacak K, Huynh TT, Sharabi Y, Mannelli M, Bratslavsky G, et al.
Low sensitivity of glucagon provocative testing for diagnosis of
pheochromocytoma. J Clin Endocrinol Metab. 2010 Jan. 95(1):238-45. [QxMD
MEDLINE Link]. [Full Text].

41. Szolar DH, Korobkin M, Reittner P, Berghold A, et al. Adrenocortical
carcinomas and adrenal pheochromocytomas: mass and enhancement loss
evaluation at delayed contrast-enhanced CT. Radiology. 2005 Feb.
234(2):479-85. [QxMD MEDLINE Link].

42. Buitenwerf E, Korteweg T, Visser A, et al. Unenhanced CT imaging is highly
sensitive to exclude pheochromocytoma: a multicenter study. Eur J
Endocrinol. 2018 Feb 21. [QxMD MEDLINE Link].

43. Park BK, Kim CK, Kwon GY, Kim JH. Re-evaluation of pheochromocytomas on
delayed contrast-enhanced CT: washout enhancement and other imaging
features. Eur Radiol. 2007 Nov. 17(11):2804-9. [QxMD MEDLINE Link].

44. Baid SK, Lai EW, Wesley RA, Ling A, Timmers HJ, Adams KT, et al. Brief
communication: radiographic contrast infusion and catecholamine release in
patients with pheochromocytoma. Ann Intern Med. 2009 Jan 6. 150(1):27-32.
[QxMD MEDLINE Link]. [Full Text].

45. Bessell-Browne R, O'Malley ME. CT of pheochromocytoma and paraganglioma:
risk of adverse events with i.v. administration of nonionic contrast
material. AJR Am J Roentgenol. 2007 Apr. 188(4):970-4. [QxMD MEDLINE Link].

46. Blake MA, Kalra MK, Maher MM, Sahani DV, Sweeney AT, Mueller PR, et al.
Pheochromocytoma: an imaging chameleon. Radiographics. 2004 Oct. 24 Suppl
1:S87-99. [QxMD MEDLINE Link].

47. Faria JF, Goldman SM, Szejnfeld J, Melo H, Kater C, Kenney P, et al.
Adrenal masses: characterization with in vivo proton MR
spectroscopy--initial experience. Radiology. 2007 Dec. 245(3):788-97. [QxMD
MEDLINE Link].

48. Kim S, Salibi N, Hardie AD, Xu J, Lim RP, Lee VS, et al. Characterization
of adrenal pheochromocytoma using respiratory-triggered proton MR
spectroscopy: initial experience. AJR Am J Roentgenol. 2009 Feb.
192(2):450-4. [QxMD MEDLINE Link].

49. Wiseman GA, Pacak K, O'Dorisio MS, Neumann DR, Waxman AD, Mankoff DA, et
al. Usefulness of 123I-MIBG scintigraphy in the evaluation of patients with
known or suspected primary or metastatic pheochromocytoma or paraganglioma:
results from a prospective multicenter trial. J Nucl Med. 2009 Sep.
50(9):1448-54. [QxMD MEDLINE Link].

50. Fottner C, Helisch A, Anlauf M, Rossmann H, Musholt TJ, Kreft A, et al.
6-18F-fluoro-L-dihydroxyphenylalanine positron emission tomography is
superior to 123I-metaiodobenzyl-guanidine scintigraphy in the detection of
extraadrenal and hereditary pheochromocytomas and paragangliomas:
correlation with vesicular monoamine transporter expression. J Clin
Endocrinol Metab. 2010 Jun. 95(6):2800-10. [QxMD MEDLINE Link].

51. Jacobson AF, Deng H, Lombard J, Lessig HJ, Black RR.
123I-meta-iodobenzylguanidine scintigraphy for the detection of
neuroblastoma and pheochromocytoma: results of a meta-analysis. J Clin
Endocrinol Metab. 2010 Jun. 95(6):2596-606. [QxMD MEDLINE Link].

52. Timmers HJ, Kozupa A, Chen CC, Carrasquillo JA, Ling A, Eisenhofer G, et
al. Superiority of fluorodeoxyglucose positron emission tomography to other
functional imaging techniques in the evaluation of metastatic
SDHB-associated pheochromocytoma and paraganglioma. J Clin Oncol. 2007 Jun
1. 25(16):2262-9. [QxMD MEDLINE Link].

53. Luster M, Karges W, Zeich K, Pauls S, Verburg FA, Dralle H, et al. Clinical
value of 18F-fluorodihydroxyphenylalanine positron emission
tomography/computed tomography (18F-DOPA PET/CT) for detecting
pheochromocytoma. Eur J Nucl Med Mol Imaging. 2010 Mar. 37(3):484-93. [QxMD
MEDLINE Link].

54. Yamamoto S, Hellman P, Wassberg C, Sundin A. 11C-hydroxyephedrine positron
emission tomography imaging of pheochromocytoma: a single center experience
over 11 years. J Clin Endocrinol Metab. 2012 Jul. 97(7):2423-32. [QxMD
MEDLINE Link].

55. Wong C, Yu R. Preoperative preparation for pheochromocytoma resection:
physician survey and clinical practice. Exp Clin Endocrinol Diabetes. 2010
Jul. 118(7):400-4. [QxMD MEDLINE Link].

56. Kwon SY, Lee KS, Lee JN, et al. Risk factors for hypertensive attack during
pheochromocytoma resection. Investig Clin Urol. 2016 May. 57 (3):184-90.
[QxMD MEDLINE Link]. [Full Text].

57. Butz JJ, Yan Q, McKenzie TJ, et al. Perioperative outcomes of syndromic
paraganglioma and pheochromocytoma resection in patients with von
Hippel-Lindau disease, multiple endocrine neoplasia type 2, or
neurofibromatosis type 1. Surgery. 2017 Sep 14. [QxMD MEDLINE Link].

58. Pravenec M, Kren V, Klír P, Simonet L, Kurtz T. Identification of genes
determining spontaneous hypertension. Review article. Sb Lek. 1991 Jun.
93(5-6):136-41. [QxMD MEDLINE Link]. [Full Text].

59. Araujo-Castro M, Garcia Centeno R, Lopez-García MC, et al. Risk factors for
intraoperative complications in pheochromocytomas. Endocr Relat Cancer.
2021 Aug 1. [QxMD MEDLINE Link].

60. Scholten A, Vriens MR, Cromheecke GJ, Borel Rinkes IH, Valk GD. Hemodynamic
instability during resection of pheochromocytoma in MEN versus non-MEN
patients. Eur J Endocrinol. 2011 Jul. 165(1):91-6. [QxMD MEDLINE Link].

61. Holscher I, van den Berg TJ, Dreijerink KMA, Engelsman AF, Nieveen van
Dijkum EJM. Recurrence Rate of Sporadic Pheochromocytomas After Curative
Adrenalectomy: A Systematic Review and Meta-analysis. J Clin Endocrinol
Metab. 2021 Jan 23. 106 (2):588-97. [QxMD MEDLINE Link].

62. Nau P, Demyttenaere S, Muscarella P, Narula V, Hazey JW, Ellison EC, et al.
Pheochromocytoma does not increase risk in laparoscopic adrenalectomy. Surg
Endosc. 2010 Nov. 24(11):2760-4. [QxMD MEDLINE Link].

63. Li QY, Li F. Laparoscopic adrenalectomy in pheochromocytoma:
retroperitoneal approach versus transperitoneal approach. J Endourol. 2010
Sep. 24(9):1441-5. [QxMD MEDLINE Link].

64. Scholten A, Valk GD, Ulfman D, Borel Rinkes IH, Vriens MR. Unilateral
subtotal adrenalectomy for pheochromocytoma in multiple endocrine neoplasia
type 2 patients: a feasible surgical strategy. Ann Surg. 2011 Dec.
254(6):1022-7. [QxMD MEDLINE Link].

65. Donatini G, Kraimps JL, Caillard C, et al. Pheochromocytoma diagnosed
during pregnancy: lessons learned from a series of ten patients. Surg
Endosc. 2018 Feb 27. [QxMD MEDLINE Link].

66. Fischer A, Kloos S, Remde H, et al. Responses to systemic therapy in
metastatic pheochromocytoma/paraganglioma: a retrospective multicenter
cohort study. Eur J Endocrinol. 2023 Nov 8. 189 (5):546-65. [QxMD MEDLINE
Link]. [Full Text].

67. [Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice
Guidelines in Oncology: Neuroendocrine Tumors, Version 2.2016. NCCN. May
25, 2016; Accessed: October 2, 2016.

68. Butz JJ, Weingarten TN, Cavalcante AN, et al. Perioperative hemodynamics
and outcomes of patients on metyrosine undergoing resection of
pheochromocytoma or paraganglioma. Int J Surg. 2017 Aug 10. 46:1-6. [QxMD
MEDLINE Link].

69. Jimenez C, Chin B, Noto R, et al. Azedra (iobenguane I 131) in patients
with metastatic and/or recurrent and/or unresectable pheochromocytoma or
paraganglioma: biochemical tumor marker results of a multicenter,
open-label pivotal phase 2 study (OR02-5). Endocrine Society (ENDO) Annual
Meeting. Chicago, IL. 2018 Mar 17.

Media Gallery

* Axial, T2-weighted magnetic resonance imaging (MRI) scan showing large left
suprarenal mass of high signal intensity on a T2-weighted image. The mass is
a pheochromocytoma.

* Abdominal computed tomography (CT) scan demonstrating left suprarenal mass of
soft-tissue attenuation representing a paraganglioma.

* Adrenalectomy specimen containing pheochromocytoma. Non-neoplastic adrenal
cortex (yellow) surrounds a small tan-red tumor in the medullary region,
representing a pheochromocytoma.

* H and E, high power, showing classic "balls of cells" feature of a
pheochromocytoma. Endocrine tumors such as a pheochromocytoma typically show
some degree of nuclear pleomorphism ("endocrine atypia") which does not
indicate malignancy.

of 4

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CONTRIBUTOR INFORMATION AND DISCLOSURES

Author

Michael A Blake, MBBCh, MRCPI, FRCR Assistant Professor, Department of
Radiology, Harvard Medical School; Staff Radiologist, Division of Abdominal
Imaging, Massachusetts General Hospital

Michael A Blake, MBBCh, MRCPI, FRCR is a member of the following medical
societies: American College of Radiology, American Roentgen Ray Society,
Radiological Society of North America, Royal College of Physicians of Ireland,
Royal College of Surgeons in Ireland

Disclosure: Received royalty from Springer for book editor.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School
of Medicine

George T Griffing, MD is a member of the following medical societies: American
Association for Physician Leadership, American Association for the Advancement
of Science, American College of Medical Practice Executives, American College of
Physicians, American Diabetes Association, American Federation for Medical
Research, American Heart Association, Central Society for Clinical and
Translational Research, Endocrine Society, International Society for Clinical
Densitometry, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Ann T Sweeney, MD Associate Professor, Department of Medicine, Division of
Endocrinology, Tufts University School of Medicine

Ann T Sweeney, MD is a member of the following medical societies: American
Association of Clinical Endocrinology, Endocrine Society

Disclosure: Nothing to disclose.

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website. We share this information with our partners on the basis of consent and
legitimate interest. You may exercise your right to consent or object to a
legitimate interest, based on a specific purpose below or at a partner level in
the link under each purpose. These choices will be signaled to our vendors
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STRICTLY NECESSARY COOKIES

Always Active

These cookies are necessary for the website to function and cannot be switched
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which amount to a request for services, such as setting your privacy
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These cookies do not store any personally identifiable information.

TARGETING COOKIES

Targeting Cookies

These cookies may be set through our site by our advertising partners. They may
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relevant adverts on other sites. They do not store directly personal
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advertising.

PERFORMANCE COOKIES

Performance Cookies

These cookies allow us to count visits and traffic sources so we can measure and
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will not be able to monitor its performance.

FUNCTIONAL COOKIES

Functional Cookies

These cookies enable the website to provide enhanced functionality and
personalisation. They may be set by us or by third party providers whose
services we have added to our pages. If you do not allow these cookies then some
or all of these services may not function properly.

STORE AND/OR ACCESS INFORMATION ON A DEVICE 55 PARTNERS CAN USE THIS PURPOSE

Store and/or access information on a device

Cookies, device or similar online identifiers (e.g. login-based identifiers,
randomly assigned identifiers, network based identifiers) together with other
information (e.g. browser type and information, language, screen size, supported
technologies etc.) can be stored or read on your device to recognise it each
time it connects to an app or to a website, for one or several of the purposes
presented here.

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PERSONALISED ADVERTISING AND CONTENT, ADVERTISING AND CONTENT MEASUREMENT,
AUDIENCE RESEARCH AND SERVICES DEVELOPMENT 62 PARTNERS CAN USE THIS PURPOSE

Personalised advertising and content, advertising and content measurement,
audience research and services development

* USE LIMITED DATA TO SELECT ADVERTISING 52 PARTNERS CAN USE THIS PURPOSE

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Advertising presented to you on this service can be based on limited data,
such as the website or app you are using, your non-precise location, your
device type or which content you are (or have been) interacting with (for
example, to limit the number of times an ad is presented to you).

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* CREATE PROFILES FOR PERSONALISED ADVERTISING 42 PARTNERS CAN USE THIS PURPOSE

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Information about your activity on this service (such as forms you submit,
content you look at) can be stored and combined with other information about
you (for example, information from your previous activity on this service and
other websites or apps) or similar users. This is then used to build or
improve a profile about you (that might include possible interests and
personal aspects). Your profile can be used (also later) to present
advertising that appears more relevant based on your possible interests by
this and other entities.

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* USE PROFILES TO SELECT PERSONALISED ADVERTISING 42 PARTNERS CAN USE THIS
PURPOSE

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Advertising presented to you on this service can be based on your advertising
profiles, which can reflect your activity on this service or other websites
or apps (like the forms you submit, content you look at), possible interests
and personal aspects.

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* CREATE PROFILES TO PERSONALISE CONTENT 15 PARTNERS CAN USE THIS PURPOSE

Switch Label

Information about your activity on this service (for instance, forms you
submit, non-advertising content you look at) can be stored and combined with
other information about you (such as your previous activity on this service
or other websites or apps) or similar users. This is then used to build or
improve a profile about you (which might for example include possible
interests and personal aspects). Your profile can be used (also later) to
present content that appears more relevant based on your possible interests,
such as by adapting the order in which content is shown to you, so that it is
even easier for you to find content that matches your interests.

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* USE PROFILES TO SELECT PERSONALISED CONTENT 13 PARTNERS CAN USE THIS PURPOSE

Switch Label

Content presented to you on this service can be based on your content
personalisation profiles, which can reflect your activity on this or other
services (for instance, the forms you submit, content you look at), possible
interests and personal aspects. This can for example be used to adapt the
order in which content is shown to you, so that it is even easier for you to
find (non-advertising) content that matches your interests.

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* MEASURE ADVERTISING PERFORMANCE 58 PARTNERS CAN USE THIS PURPOSE

Switch Label

Information regarding which advertising is presented to you and how you
interact with it can be used to determine how well an advert has worked for
you or other users and whether the goals of the advertising were reached. For
instance, whether you saw an ad, whether you clicked on it, whether it led
you to buy a product or visit a website, etc. This is very helpful to
understand the relevance of advertising campaigns.

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* MEASURE CONTENT PERFORMANCE 21 PARTNERS CAN USE THIS PURPOSE

Switch Label

Information regarding which content is presented to you and how you interact
with it can be used to determine whether the (non-advertising) content e.g.
reached its intended audience and matched your interests. For instance,
whether you read an article, watch a video, listen to a podcast or look at a
product description, how long you spent on this service and the web pages you
visit etc. This is very helpful to understand the relevance of
(non-advertising) content that is shown to you.

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* UNDERSTAND AUDIENCES THROUGH STATISTICS OR COMBINATIONS OF DATA FROM
DIFFERENT SOURCES 37 PARTNERS CAN USE THIS PURPOSE

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Reports can be generated based on the combination of data sets (like user
profiles, statistics, market research, analytics data) regarding your
interactions and those of other users with advertising or (non-advertising)
content to identify common characteristics (for instance, to determine which
target audiences are more receptive to an ad campaign or to certain
contents).

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* DEVELOP AND IMPROVE SERVICES 53 PARTNERS CAN USE THIS PURPOSE

Switch Label

Information about your activity on this service, such as your interaction
with ads or content, can be very helpful to improve products and services and
to build new products and services based on user interactions, the type of
audience, etc. This specific purpose does not include the development or
improvement of user profiles and identifiers.

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* USE LIMITED DATA TO SELECT CONTENT 10 PARTNERS CAN USE THIS PURPOSE

Switch Label

Content presented to you on this service can be based on limited data, such
as the website or app you are using, your non-precise location, your device
type, or which content you are (or have been) interacting with (for example,
to limit the number of times a video or an article is presented to you).

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USE PRECISE GEOLOCATION DATA 18 PARTNERS CAN USE THIS SPECIAL FEATURE

Use precise geolocation data

With your acceptance, your precise location (within a radius of less than 500
metres) may be used in support of the purposes explained in this notice.

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ACTIVELY SCAN DEVICE CHARACTERISTICS FOR IDENTIFICATION 3 PARTNERS CAN USE THIS
SPECIAL FEATURE

Actively scan device characteristics for identification

With your acceptance, certain characteristics specific to your device might be
requested and used to distinguish it from other devices (such as the installed
fonts or plugins, the resolution of your screen) in support of the purposes
explained in this notice.

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ENSURE SECURITY, PREVENT AND DETECT FRAUD, AND FIX ERRORS 50 PARTNERS CAN USE
THIS SPECIAL PURPOSE

Always Active

Your data can be used to monitor for and prevent unusual and possibly fraudulent
activity (for example, regarding advertising, ad clicks by bots), and ensure
systems and processes work properly and securely. It can also be used to correct
any problems you, the publisher or the advertiser may encounter in the delivery
of content and ads and in your interaction with them.

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DELIVER AND PRESENT ADVERTISING AND CONTENT 44 PARTNERS CAN USE THIS SPECIAL
PURPOSE

Always Active

Certain information (like an IP address or device capabilities) is used to
ensure the technical compatibility of the content or advertising, and to
facilitate the transmission of the content or ad to your device.

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MATCH AND COMBINE DATA FROM OTHER DATA SOURCES 41 PARTNERS CAN USE THIS FEATURE

Always Active

Information about your activity on this service may be matched and combined with
other information relating to you and originating from various sources (for
instance your activity on a separate online service, your use of a loyalty card
in-store, or your answers to a survey), in support of the purposes explained in
this notice.

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LINK DIFFERENT DEVICES 35 PARTNERS CAN USE THIS FEATURE

Always Active

In support of the purposes explained in this notice, your device might be
considered as likely linked to other devices that belong to you or your
household (for instance because you are logged in to the same service on both
your phone and your computer, or because you may use the same Internet
connection on both devices).

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IDENTIFY DEVICES BASED ON INFORMATION TRANSMITTED AUTOMATICALLY 40 PARTNERS CAN
USE THIS FEATURE

Always Active

Your device might be distinguished from other devices based on information it
automatically sends when accessing the Internet (for instance, the IP address of
your Internet connection or the type of browser you are using) in support of the
purposes exposed in this notice.

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