The adrenal glands are composed of an outer cortex and inner medulla that arise from different embryonic layers. Phaeochromocytomas are rare catecholamine-secreting tumors that originate in the adrenal medulla. Diagnosis involves measuring urinary or plasma metanephrines and imaging tests. Treatment requires preoperative alpha-blockade to prevent dangerous blood pressure fluctuations during tumor resection surgery. Lifelong follow-up is needed due to the risk of recurrence or metastasis.

2. Dr.Mostafa Hegazy

3.  The adrenal or suprarenal glands are two endocrine organs in one;
an outer cortex and an inner medulla, each with distinct
embryologic, anatomic, histologic, and secretory features.
 The two functional parts, the cortex and the medulla, arise from
different blastodermic layers:
 Mesodermal cells: form the adrenal cortex
 Neuroectodermal cells: migrate to the cortex during
embryogenesis and form the adrenal medulla.

4.  The adrenal glands are situated at the upper
poles of the kidneys in the retroperitoneum
within Gerota’s capsule at the level of the
eleventh ribs.
 The weight is approximately 4 g.
 The right adrenal gland: is located between the
right liver lobe and the diaphragm, close to and
partly behind the inferior vena cava.
 The left adrenal gland: lies on the upper pole of
the left kidney and reaches the renal pedicle. It is
covered by the pancreatic tail and the spleen.

5.  The arterial blood supply:
 Superior adrenal arteries derived from the
inferior phrenic artery,
 Middle adrenal arteries derived from the
aorta,
 Inferior adrenal arteries derived from the
renal artery.
 Venous Drainge: a large adrenal vein drains
on the right side into the vena cava and on
the left side into the renal vein.

6.  The adrenal cortex: is characterised by a zonal configuration.
 Zona Glomerulosa: The outer zona glomerulosa contains small, compact
cells.
 Zona Fasciculata: The zona fasciculata can be identified by the larger, lipoid
cells, which are arranged in radial columns.
 Zona Reticularis: Compact and pigmented cells characterise the inner zona
reticularis.
 The adrenal medulla: consists of a thin layer of large chromaffin cells, which
store catecholamine granules.

7. DISORDERS OFTHE ADRENAL MEDULLA

8. It is a tumour of the adrenal
medulla, which is derived from
chromaffin cells and which
produces catecholamines.

9.  The prevalence of phaeochromocytoma in
patients with hypertension is 0.1–0.6% with
an overall prevalence of 0.05% in autopsy
series.
 In total, 4% of incidentalomas are
phaeochromocytomas.

10.  Sporadic phaeochromocytomas occur after the
fourth decade whereas patients with hereditary
forms are diagnosed earlier.
 Phaeochromocytoma is known as the ‘10% tumour’
as 10% of tumours are inherited, 10% are extra-
adrenal, 10% are malignant, 10% are bilateral and
10% occur in children.

11. Hereditary phaeochromocytomas occur in several
tumour syndromes:
1-Multiple endocrine neoplasia type 2 (MEN 2):
an autosomal dominant inherited disorder that
is caused by activating germline mutations of
the RET protooncogene.

12. 2-Familial paraganglioma (PG) syndrome:
 Extra-adrenal tumors, also called functional paragangliomas,
may be found at sites of sympathetic ganglia in the organ of
Zuckerkandl, neck, mediastinum, abdomen, and pelvis .
 Glomus tumours of the carotid body and extra adrenal
paraganglioma are characteristic in this hereditary tumour
syndrome, which is caused by germline mutations within the
succinate dehydrogenase complex subunit B (SDHB) and SDHD
genes.

13. 3-von Hippel–Lindau (VHL) syndrome:
 This syndrome also includes early-onset bilateral kidney
tumours, phaeochromocytomas, retinal angioma,
cerebellar and spinal haemangioblastomas and pancreatic
tumours., and epididymal cystadenomas.
 The incidence of pheochromocytomas in the syndrome is
approximately 14%.
 Patients have a germline mutation in theVHL gene

14. 4-Neurofibromatosis (NF) type 1:
 Phaeochromocytomas in combination with fibromas on
the skin and mucosae (‘cafe-au-lait’ skin spots) are
indicative of a germline mutation in the NF1 gene. Other
 Other neuroectodermal disorders (Sturge-Weber
syndrome and tuberous sclerosis), Carney's syndrome
(gastric epithelioid leiomyosarcoma, pulmonary
chondroma, and extra-adrenal paraganglioma), MEN1
syndrome,

15. Pathophysiology

18. • Catecholamines exhibit peripheral nervous system
excitatory and inhibitory effects as well as actions in
the CNS such as respiratory stimulation and an
increase in psychomotor activity.
• The excitatory effects are exerted upon smooth
muscle cells of the vessels that supply blood to the
skin and mucous membranes.

19. • Cardiac function is also subject to excitatory effects, which lead to
an increase in heart rate and in the force of contraction.
• Inhibitory effects,are exerted upon smooth muscle of the gut, the
bronchial tree, and blood vessels of the skeletal muscle.
• In addition to their effects as neurotransmitters, norepinephrine
and epinephrine can influence the rate of metabolism by
modulating insulin secretion and by increasing the rate of
glycogenolysis and fatty acid metabolism.
• Abnormalities in carbohydrate metabolism such as insulin
resistance, impaired fasting glucose, type 2 DM can occure

20.  Phaeochromocytomas are greyish-pink on the cut
surface and are usually highly vascularised. Areas
of haemorrhage or necrosis are often observed .
 Microscopically, tumour cells are polygonal but
the configuration varies considerably.

21.  The differentiation between malignant and benign tumours is
difficult, except if metastases are present.
 Phaeochromocytomas may also produce calcitonin, ACTH,
vasoactive intestinal polypeptide (VIP) and parathyroid
hormone- related protein (PTHrP).
 In patients with MEN 2, the onset of phaeochromocytoma is
preceded by adrenomedullary hyperplasia, usually bilateral.
 Phaeochromocytoma is rarely malignant in MEN 2.

22. DIAGNOSIS

23. Signs and Symptoms

24. Episodic headache
Sweating
Tachycardia

25. Clinical signs of phaeochromocytoma
 Symptoms and signs are caused by catecholamine
excess and can be continuous or intermittent.
 In total, 90% of patients with the combination of
headache, palpitations and sweating have a
phaeochromocytoma.
 Paroxysms may be precipitated by physical
training, induction of general anaesthesia and
numerous drugs and agents (contrast media,
tricyclic antidepressive drugs, metoclopramide
and opiates).

26.  Hypertension may occur continuously, be intermittent
or absent.
 A subset of patients is asymptomatic.
 More than 20% of apparently sporadic
phaeochromocytomas are caused by germline
mutations in the RET, SDHB, SDHD and NF1 genes;
genetic testing for these genes is therefore generally
recommended.

27. Symptoms Prevalence (%)
 Hypertension: 80–90
 Paroxysmal 50–60
 Continuous 30
 Headache 60–90
 Sweating 50–70
 Palpitation 50–70

28. Symptoms Prevalence (%)
 Pallor 40–45
 Weight loss 20–40
 Hyperglycaemia 40
 Nausea 20–40
 Psychological effects 20–40

29.  Hyperadrenergic spells eg self-limited episodes of
nonexertional palpitations, diaphoresis, headache,
tremor, pallor
 Resistant hypertension (<0.2% of patients with HTN
have pheochromocytoma)
 Pre-disposing familial syndrome eg MEN 2, NF1,VHL
 Family history of pheochromocytoma

30.  Incidentally discovered adrenal mass: 3-10% prove to be
pheochromocytomas
 Pressor response during anesthesia, surgery or angiography.
 Onset of HTN < 20 years old
 Idiopathic dilated cardiomyopathy
 History of gastric stromal tumor or pulmonary chondromas
(CarneyTriad)

31.  Historically: measured 24 hour urinary excretion of
catecholamines and total metanephrines
 Superior test: plasma fractionated metanephrines via liquid
chromatography with electrochemical detection or tandem
mass spectrometry.
 Recent studies have shown that plasma metanephrines are
the most reliable tests to identify pheochromocytomas,
with sensitivity approaching 100%.

32.  96-100% sensitive and 85-89% specific and falls to 77% in
patients >60 years old
 Predictive value is high and normal test excludes
pheochromocytoma except in patients with early preclinical
disease and those with strictly dopamine-secreting tumors.
 Tricyclic antidepressants interfere with assay most
frequently

33.  Clonidine suppression test is confirmatory when
plasma fractionated metanephrines are positive: 0.3
mg is administered orally, plasma catecholamines are
measured before and 3 hours after the dose.
 Clonidine will suppress catecholamines if excess is
due to essential hypertension, but will remain
elevated in pheochromocytoma

34.  Follow up with CT or MRI of abdomen and
pelvis
 Consider Metaiodobenzylguanidine (MIBG)
scintgraphy where a compound resembling
norepinephrine is taken up by adrenal tissue
if clinical suspicion remains high

35.  TCAs
 Levodopa
 Drugs containing adrenergic receptor agonists
eg decongestants
 Amphetamines
 Buspirone and most psychoactive agents

36.  Prochlorperazine
 Reserpine
 Withdrawal from clonidine
 Ethanol
 acetominophen

37.  The first step in the diagnosis of a
phaeochromocytoma is the determination of
adrenaline, noradrenaline, metanephrine and
normetanephrine levels in a 24-hour urine collection.
 Catecholamine levels that exceed the normal range
by 2–40 times will be found in affected patients.

38.  Determination of plasma-free metanephrine
and normetanephrine levels is a recently
available test that has a high sensitivity.
 Biochemical tests should be performed at
least twice.

39.  The biochemical diagnosis is followed by the
localisation of the phaeochromocytoma and/or
metastases.
 MRI is preferred because contrast media used for CT
scans can provoke paroxysms.
 Classically, phaeochromocytomas show a‘Swiss
cheese’ configuration .

40.  123I-MIBG (metaiodobenzylguanidine) single-photon
emission computerised tomography (SPECT) will
identify about 90% of primary tumours and is
essential for the detection of multiple extra-adrenal
tumours and metastases

41.  10% of tumors are extraadrenal, but 95% are within
abdomen and pelvis
 About 10% of all catecholamine-secreting tumors are
malignant
 Histologically and biochemically identical to benign
counterparts
 Local invasion or distant metastases can occur as long as
20 years after resection

42. Treatment

43.  Start alpha-adrenergic blocker 7-10 days preoperatively
 Phenoxybenzamine is drug of choice: irreversible, long-
acting, non-specific alpha-adrenergic agent.
 Initial dose is 10 mg b.i.d.; dose is increased by 10-20 mg in
divided doses every 2-3 days; final dose usually 20-100 mg
daily

44.  Goal BP <120/80 seated and SBP > 90 standing
 High salt (> 5000 mg daily) recommended on 3rd day to
counteract catecholamine-induced volume contraction
and orthostasis, though caution advised in patients with
CHF or CRI.
 Following adequate alpha-blockade, beta blockade is
initiated 2-3 days pre-operatively eg. Propranolol 10 mg
q.6.h

45.  NEVER start beta blockade first; unopposed alpha
adrenergic stimulation can lead to further elevation in
blood pressure
 Long-term treatment with selective alpha1-
adrenergic blockers such as prazosin, terazosin,
doxazosin.
 Calcium channel blockers are probably as effective,
eg. Nicardipine 30 mg b.i.d.

46.  Addition of metyrosine, a direct catecholamine
synthesis inhibitor, may improve perioperative course,
though most institutions reserve for those patients who
cannot tolerate the typical alpha + beta blockade
combination.
 Side effects include sedation, depression,
diarrhea,anxiety, nightmares, crystalluria and
urolithiasis, galactorrhea, and extrapyramidal signs

47.  Laparoscopic resection is now routine in the
treatment of phaeochromocytoma.
 If the tumour is larger than 8–10 cm or radiological
signs of malignancy are detected an open approach
should be considered.
preoperative
 Once a phaeochromocytoma has been diagnosed, an
α- adrenoreceptor blocker (phenoxybenzamine) is
used to block catecholamine excess and its
consequences during surgery.
 With adequate medical pre-treatment, the
perioperative mortality rate has decreased from 20–
45% to less than 3%.

48.  A dose of 20 mg of phenoxybenzamine initially should
be increased daily by 10 mg until a daily dose of 100–
160 mg is achieved and the patient reports
symptomatic postural hypotension.
 Additional β-blockade is required if tachycardia or
arrhythmias develop; this should not be introduced
until the patient is α-blocked.

49. Peroperative
 With adequate α-blockade preoperatively,
anaesthesia should not differ from that used in
patients with a non-functioning adrenal tumour;
however, in some patients, dramatic changes in heart
rate and blood pressure may occur and require sudden
administration of pressor or vasodilator agents.

50.  A central venous catheter and invasive arterial
monitoring are essential.
 Special attention is required when the adrenal vein is
ligated as a sudden drop in blood pressure may occur.
 Rarely, the infusion of large volumes of fluid or even
administration of adrenaline can be necessary.
Postoperative
 Patients should be observed for 24 hours in the
intensive care unit (ICU) as hypovolaemia and
hypoglycaemia may occur.

51.  Biochemical cure should be confirmed by an
assessment of catecholamines 2–3 weeks
postoperatively.
 Lifelong yearly biochemical tests should be
performed to identify recurrent, metastatic or
metachronous phaeochromocytoma