Phreochromocytoma : overvew, introduction, adrenal gland anatomy and physiology, adrenl gland tumor classification, epidemiology, clinical features, investigations

1. Pheochromocytoma
Dr. Rajshree Singh
Intern doctor
Shree Birendra Hospital
Chaunni, Kathmanu

2. Outline
• Anatomy
• Embryology
• Physiology &
biochemistry
• Disease of adrenal
gland
• Pheochromocytoma
– Introduction
– Epidemiology
– Risk factors
– Clinical features
– Investigation
– Treatment
• Case presentation
• Published papers and
researches
• References

3. Anatomy

4. Anatomy
• measures 5 x 3 x 1 cm and weighs 4 to 5 g
• Right gland is pyramidal shaped ; in close proximity to
the right hemidiaphragm, liver, and inferior vena cava
(IVC)
• Left adrenal is closely associated with the aorta,spleen,
and tail of the pancreas.
• Divided into
– Cortex—85%
– Medulla—15%

5. Embryology
• Mesodermal cells form the adrenal cortex
• Neuroectodermal cells migrate to the cortex from
the neural crest during embryogenesis and form the
adrenal medulla.
• neural crest cells also migrate to the para-aortic and
paravertebral areas
• Most extra-adrenal neural tissue regresses but may
persist at several sites.

6. Embryology
• Largest of these is located
to the left of the aortic
bifurcation near the
inferior mesenteric artery
origin and is designated
as the organ of
Zuckerkandl.
• Adrenal medullary tissue
also may be found in
neck, urinary bladder, and
para-aortic regions.

7. Physiology
• Adrenal cortex contains three layers:
– Zona glomerulosa secretes mineralocorticoids.
– Zona fasciculata secretes glucocorticoids.
– Zona reticularis secretes sex hormones.
• Adrenal medulla
– up to 10 to 20% of the gland's volume and is reddish
brown in color
– produces the catecholamine : epinephrine and
norepinephrine.
– cells are arranged in cords and are polyhedral in shape
– often are referred to as chromaffin cells because they
stain specifically with chromium salts.

8. Physiology
• Phenylethanolamine N-methyltransferase, which
converts norepinephrine to epinephrine, is only
present in the adrenal medulla and the organ of
Zuckerkandl.
• Catecholamines are stored in granules called
chromogranins.
• Hormonal secretion is stimulated by various stress
stimuli.
• In the circulation, these proteins are bound to
albumin.

9. Physiology
• Catecholamines are cleared by reuptake by
sympathetic nerve endings & peripheral inactivation
by catechol O-methyltransferase and monoamine
oxidase & excretion by kidneys.
• Metabolism of catecholamines takes place in the
liver and kidneys by the formation of metabolites
such as metanephrines, normetanephrines, and
VMA, which may undergo further glucuronidation or
sulfation before being excreted in the urine

10. Disease of adrenal glands
Adrenal cortex
• Incidentaloma
• Non-functioning adenoma
• Cushing’s adenoma
• Adrenocortical carcinoma
• Myelolipoma
• Cyst
• Metastases
• Conn’s adenoma
Adrenal medulla
• Pheochromocytoma
• Malignant
pheochromocytoma
• Neuroblastoma

11. Pheochromocytoma
• It is a tumour arising from chromaffin cells, from the
adrenal medulla but can also arise from extraadrenal
chromaffin tissues (Organ of Zuckerkandl).
• It is catecholamine secreting tumours
• Pheochromocytomas were first identified by Frankel in
1885, but were not named as such until 1912 by Pick,
who noted the characteristic chromaffin reaction of
the tumor cells.
• The first successful adrenalectomies for
pheochromocytoma were performed by Roux in
Switzerland, and Charles Mayo in the United States.

12. Epidemiology
• prevalence of phaeochromocytoma in patients
with hypertension is 0.1–0.6 per cent
• an overall prevalence of 0.05 per cent in autopsy
series.
• In total, 4 per cent of incidentalomas are
phaeochromocytomas.
• They can occur at any age with a peak incidence
in the fourth and fifth decades of life
• Have no gender predilection

13. the 10 percent tumor
• 10% are bilateral
• 10% are malignant
• 10% occur in pediatric patients
• 10% are extra-adrenal
• 10% are familial
• 10% multiple
• 10% not associated with hypertension
• 10% calcified

14. Risk factors
• occur in families with MEN2A and MEN2B, in
approximately 50% of patients
• von Hippel-Lindau (VHL) disease
• included within the tumor spectrum of
neurofibromatosis type 1 (NF1 gene) and other
neuroectodermal disorders (Sturge-Weber syndrome
and tuberous sclerosis), Carney's syndrome, MEN1
syndrome
• familial paraganglioma & pheochromocytoma syndrome
caused by mutations in the succinyl dehydrogenase
family of genes (SDHB, SDHC, and SDHD).

15. Clinical features
• classic triad : Headache, palpitations, and diaphoresis
• Commonest presentation is severe headache.
• Symptoms of sympathetic over activity such as
anxiety, tremulousness, paresthesias, flushing, ,
weakness, pallor, blurred vision, chest pain,
shortness of breath, abdominal pain, nausea,
vomiting, and others are nonspecific and may be
episodic in nature.
• Symptoms can be incited by a range of stimuli
including exercise, micturition, and defecation

16. Symptoms

17. Clinical Signs
• most common clinical sign is hypertension.
• Pheochromocytomas are one of the few curable
causes of hypertension and are found in 0.1 to
0.2% of hypertensive patients.
• Hypertension related to this tumor may be
paroxysmal with intervening normotension,
sustained with paroxysms or sustained
hypertension alone.
• As an abdominal mass which is nonmobile,
smooth, does not move with respiration, crossing
the midline

18. Complications
• Cardiovascular complications such as
myocardial infarction and arrhythmias
• Sudden death may occur in patients with
undiagnosed tumors who undergo other
surgeries or biopsy.
• precipitate hypertensive encephalopathy &
cerebral haemorrhage.
• Panic attacks

19. Differential diagnosis
• Hyperthyroidism
• Anxiety status
• Cardiac conditions
• Carcinoids (functioning)

20. Investigations
• 24-hour urine samples for catecholamines and their
metabolites
• plasma metanephrine levels.
• Urinary metanephrines are highly senisitive &
specific, whereas VMA measurements are slightly
less in so.
• False-positive VMA tests may result from ingestion of
caffeine, raw fruits, or medications ( -methyldopa).
• Fractionated urinary catecholamines also are very
sensitive but less specific for pheochromocytomas.

21. Investigations
• Many physiologic and pathologic states can alter the
levels of plasma catecholamines. Hence, they are
less accurate than urinary tests.
• Both epinephrine and norepinephrine should be
measured, as tumors often secrete one or the other
hormone. They have cutoff values of 2000 pg/mL for
norepinephrine and 200 pg/mL for epinephrine.
• Clonidine is an agent that suppresses neurogenically
mediated catecholamine excess but not secretion
from pheochromocytomas.

22. Investigations
• A normal clonidine suppression test is defined by a
decrease of basal catecholamine levels to <500 pg/mL
within 2 to 3 hours after an oral dose of 0.3 mg of
clonidine.
• Chromogranin A is a monomeric, acidic protein, which is
stored in the adrenal medulla and other neuroendocrine
tumors and released along with catecholamine
hormones. It is useful in conjunction with catecholamine
measurement for diagnosing pheochromocytomas.
• Recent studies have shown that plasma metanephrines
are the most reliable tests to identify
pheochromocytomas, with sensitivity approaching 100%.

23. • Add the table with cutoff biochemical values
which is table 41-4

24. Radiologic Studies
• CT scans are 85 to 95% sensitive and 70 to 100%
specific for pheochromocytomas.
• Images should include the region from the
diaphragm to the aortic bifurcation so as to include
the organ of Zuckerkandl.
• CT scans do not provide functional information and
cannot definitively diagnose pheochromocytomas.
• MRI scans are 95% sensitive and almost 100%
specific for pheochromocytomas because these
tumors have a characteristic appearance on T2-
weighted images or after gadolinium.

25. A left-sided pheochromocytoma (arrows) imaged by a
computed tomography scan of the abdomen

27. Radiologic Studies
• Metaiodobenzylguanidine (MIBG) is taken up and
concentrated by vesicles in the adrenal medullar cells
because its structure is similar to norepinephrine.
• Normal adrenal medullary tissue does not take up
appreciable MIBG.
• 131I radiolabeled MIBG is, therefore, useful for
localizing pheochromocytomas, especially those in
ectopic positions.
• This test has a reported sensitivity of 77 to 89% and
specificity ranging from 88 to 100%.

28. A left-sided pheochromocytoma (arrows)
MIBG scan viewed posteriorly

29. Treatment

31. Malignant pheochromocytoma

32. Case presentation

33. Newer concepts in approach to
Pheochromocytoma

34. References
• Sabiston Textbook of Surgery, 20th edition
• Schwartz's Principles of Surgery, 9th Edition
• Bailey And Love's Short Practice of Surgery
26th Ed
• SRB's Manual of Surgery, 4E
• PubMed

35. Thank you