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.
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,
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.
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.
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
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
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
