ANATOMI DAN FISIOLOGI

KELENJAR ADRENAL

Dr. Bernhard Arianto Purba, M.Kes., AIFO

Textbooks
• Guyton, A.C & Hall, J.E. 2006. Textbook of Medical
Physiology. The 11th edition. Philadelphia: Elsevier-
Saunders: 945-960, 749-760.
• Brooks, G.A. & Fahey, T.D. 1985. Exercise Physiology.
Human Bioenergetics and Sts Aplications. New York : Mac
Millan Publishing Company: 122-143.
• Foss, M.L. & Keteyian, S.J. 1998. Fox’s Physiological Basis
for Exercise and Sport. 4th ed. New York : W.B. Saunders
Company: 471-491.
• Astrand, P.O. and Rodahl, K. 1986. Textbook of Work
Pysiology, Physiological Bases of Exercise. New York :
McGraw—Hill.
• Braunwald, Pauci, et al.2008. Harrison's PRINCIPLES OF
INTERNAL MEDICINE. Seventeenth Edition. New York :
McGraw—Hill: Chapter 336, 337.
• Kronenberg, and Melmed. 2008. WILLIAMS TEXTBOOK OF
ENDOCRINOLOGY . The 11th edition . Philadelphia:
Elsevier-Saunders: 445-494, 505-531.
THE ADRENAL
GLANDS
 Also called “suprarenal
glands”
 One at the cranial pole of each
kidney
 Left and right-sided glands
 Left gland is crescentic and right
gland is pyramidal
 Has head, body, and tail
 Measures 5 x 3 x 1 cm
 Normal weight of 4-6 grams
each after dissection of fat
They lie at the superior poles of the two
kidneys. Each gland is composed of two
distinct parts:

1. Adrenal Cortex – 80%

2. Adrenal Medulla-
20%
CORTICOSTERIODS – group of hormones secreted by the
adrenal cortex. These are synthesized from the steroid
Cholesterol. The following are the ADRENOCORTICAL
HORMONES:

1. Mineralocorticoids – affect electrolytes of the ECF – Sodium

and Potassium

2. Glucocorticoids – Exhibit an important effect in increasing

blood glucose concentration

3. Androgenic hormones

ALDOSTERONE – principal mineralocorticoid

CORTISOL – principal glucocorticoid
LAYERS OF ADRENAL CORTEX AND SECRETION
1. Zona Glomerulosa
- constitutes about 15% of the adrenal cortex

- cells are the only ones secreting Aldosterone

- they contain enzyme aldosterone synthase

necessary for synthesis of aldosterone

- secretion is controlled by ECF conc. of

Angiotensin II and Potassium

Novantrone Main Presentation Version 7.0 - 2/22/19 M-9

2. Zona Fasciculata
- constitutes about 75% of the adrenal
cortex
- middle and widest layer
- secretes the glucocorticoids cortisol
and corticosterone and small
amounts of adrenal androgens and
estrogens
- secretion is controlled by
hypothalamic- pituitary axis via
3. Zona Reticularis
- secretes the adrenal androgen
Dehydroepiandrosterone (DHEA) and
androstenedione and small amounts of
estrogen and some glucocorticoids

- secretion is regulated by ACTH and other factor

such as cortical androgen-stimulating
hormone from the pituitary
GLOMERULOSA FASCICULATA RETICULARIS

Cholesterol Cholesterol Cholesterol

Pregnenolone Pregnenolone Pregnenolone

Progesterone 17-OH- 17-OH-

pregnenolone pregnenolone

Deoxycortico- 17-OH-
progesterone
sterone
Dehydroepi-
11-deoxycortisol androsterone
Corticosterone

cortisol androstenedione
aldosterone
 21 CH3
18 =O
Lipoprotein 12 17
11 16
Acetate 13
1 19
2 15
9
CH3 10 8 14
5 pathway CH3
=O HO 3 5 7
HO Cholesterol 4 6 =O
OH Pregnenolone
5 pathway
O

HO O Progesterone CH2OH
17-OH-pregnenolone
=O
O
OH Dehyroepiandrosterone
17-OH-progesterone
(DHEA)

OH O
Androstanediol Deoxycorticosterone (DOC)
O 11-deoxycortisol
-androstenedione
4

Corticosterone

Esterone CH2OH O CH2OH CH3

OH OH
O Testosterone =O CH =O =O
OH HO

HO H HO O O O
Dihydrotestosterone Estradiol Cortisol Aldosterone Progesterone
Pathways of syntheis of the major classes of steroid hormones, Cholesterol is devided from acetate by sybthesis or from
lipoprotein partcles. The numbering of the steroid molecule is shown for pregnenolone. The major pathways thought to be used
are shown.
 Relative anti- Relative Na Duration of Appox equiv
compound inflam effect retain potency actions dose (mg)

Cortisol (HC) 1 1 S 20
Prednisone 0 0 - -
Prednisolone 4 0.8 I 5
4 - I 5
-m-prednisolone
5 0.5 I 4
Fluorocortisone
10 125 S -
11-desoxycortisol
0 0 - -
Cortisone 0.8
0.8 S 25
Corticosterone 0.35 15 S -
Triamcinolone 5 0 I 4
Betamethasone 25 0 L 0.75
dexamethasone 25 0 L 0.75

Relative potencies and equivalent

doses of corticosteroids
 More Important Glucocorticoid
Hormones including Synthetic ones:
1. Mineralocorticoids

- Aldosterone (very potent, accounts for 90% of all

mineralocorticoid activity
- Desoxycorticosterone (1/30 as potent as aldosterone,
but very small quantities secreted
- Corticosterone (slight minralocorticoid activity)
- 9a-Fluococortisol (synthetic, slightly more potent
than aldosterone)
- Cortisol (very slight mineralocorticoid activity, but
large quantity secreted
- Cortisone (synthetic, slight mineralocorticoid activity)
FUNCTIONS OF MINERALOCORTICOID –
Aldosterone
1. Renal and Circulatory Effects of Aldosterone
a. Aldosterone Increases Renal Tubular
Reabsorption of Sodium and Secretion of
Potassium – especially in the principal cells of
the collecting tubules, and to lesser extent in the
distal tubules and collecting ducts
b. Excess Aldosterone Increases ECF Volume and
Arterial Pressure but Has Only a Small Effect
on Plasma Sodium Concentration
c. Excess Aldosterone Causes Hypokalemia and
Muscle Weakness; Too little Aldosterone Causes
Hyperkalemia and Cardiac Toxicity
Regulation of Sodium Balance: Aldosterone
Hypokalemia causes severe muscle
weakness caused by alteration of the
electrical excitability of the nerve and
muscle fiber membranes which
prevents transmission of normal
action potential

Deficient Aldosterone – results to

cardiac toxicity, including weakness of
heart contraction and development of
arrhythmia
d. Excess Aldosterone Increases Tubular Hydrogen Ion
Secretion with Resultant Mild Alkalosis

- secretion hydrogen ion in exchange for sodium

in the intercalated cells of the cortical collecting
tubules

2. Aldosterone Stimulates sodium and Potassium

Transport in Sweat Glands, Salivary Glands and
Intestinal Epithelial Cells

- same effects as it has on the renal tubules

Novantrone Main Presentation Version 7.0 - 2/22/19 M-20

Cellular Mechanism of Aldosterone Action

1. Aldosterone diffuses readily to the interior of the

tubular epithelial cells

2. In the cytoplasm of the tubular cells, aldosterone

combines with specific cytoplasmic receptor protein

3. Aldosterone-receptor complex diffuses into the

nucleus, inducing RNA to form messenger RNA

4. The mRNA diffuses back into the cytoplasm

operating in conjunction with the ribosomes causes
protein formation
FACTORS THAT PLAY ESSENTIAL ROLES
IN THE REGULATION OF ALDOSTERONE
1. Increased potassium ion concentration in
extracellular fluid greatly increases aldosterone
secretion
2. Increased activity of renin-angiotensin system
(angiotensin II) greatly increased aldosteron
secretion
3. Increased sodium ion concentration in the
extracellular fluid very slightly decreases
aldosteron secretion
4. ACTH from the anterior pituitary gland is
necessary for aldosterone secretion but has
little effect in controlling the rate of secretion
 FACTORS THAT
PLAY ESSENTIAL
ROLES IN THE
REGULATION OF
ALDOSTERONE
 Natriuretic Peptide

• ANP is released by cardiac muscle cells

• In response to abnormal stretching of heart walls
caused by:
– elevated blood pressure
– an increase in blood volume
• Reduce thirst
• Block release of ADH and aldosterone
• Cause diuresis
• Lower blood pressure and plasma volume
Role of Atrial Natriuretic Peptide
2. Glucocorticoid
- Cortisol (very potent, accounts for about 95% of
all glucocorticoid activity
- Corticosterone (provides 4% of total
glucocorticoid) activity, much less potent than
cortisol)
- Cortisone (synthetic, almost as potent as
cortisol)
- Prednisone (synthetic, four times as potent as
cortisol)
- Methyprednisone (synthetic, five tmes as potent
as cortisol)
- Dexamethasone (synthetic, 30 times as potent as
The Intense Glucocorticoid
Activity of Dexamethasone, has
almost zero mineralocorticoid
activity, thus is important drug
for stimulating specific
glucocorticoid activity
 Functions of the Glucocorticoids
1- Metabolic effects:
A. Carbohydrate metabolism:
Stimulation of gluconeogenesis by the liver (rate increases 6
to 10 fold):
o enzymes required to convert amino acids into glucose are
increased (activation of DNA transcription)
o In extra hepatic tissues; Cortisol stimulates protein catabolism
(i.e. mobilization of amino acids from extra-hepatic tissues
(mainly skeletal muscles).
Decreased glucose utilization by the cells
Elevated blood glucose concentration and “adrenal
diabetes” (chronic increase of insulin  fail to produce)
 2. Effect of glucocorticoids :
on protein metabolism

Reduction in Cellular Protein

• decreased protein synthesis
• proteocatabolic effect in all body cells except of
the liver
Proteoanabolic effect in the liver
– enhanced liver proteins
– increased plasma proteins
Increased blood amino acids
– decreased amino acids transport into extrahepatic
tissues (muscles, lymphatic tissues)
– Enhanced transport into hepatic cells
(prolong wound healing)
3. Effect of glucocorticoids : on fat metabolism

• mobilization of fatty acids from adipose tissue

• moderately enhance the oxidation of fatty acids
(lower glucose utilization stimulates the cells to
utilize energy from fatty acids)
 4. Anti inflammatory effect: Cortisol in large
pharmacological dose Inhibit inflammatory reaction because
it:
 Stabilizes lysozymes membrane.
 Inhibit the release of vasodilator substances e.g. Kinins.
 Decreases capillary permeability and edema formation.
 Suppresses immune system especially the T – lymphocytes.
 Attenuates fever because reduces the release of interleukin-1
from white blood
5. Anti-allergic effect: Cortisol in pharmacological doses:
o Inhibit histamine release from mast cells.
o Decreases the Eosinophile and lymphocytes.
6. Resistance to stress: Cortisol increases the body
resistance to stress through:
• Increasing vascular reactivity to circulating Catecholamine.
• Mobilization of fatty acids as a source of energy during stress.
• Maintenance of plasma volume.
Regulation of cortisol secretion

paraventricular nuclei CRH

of hypothalamus

corticotrops ACTH
of adenohypophysis

cortisol adrenal
cortex
 Hormone

Receptor

Extracellular side

Cell membrane

Enzyme Cytosolic side

G protein
ATP cAMP (Second Messenger)

cAMP

Inactive R
Protein kinase A cAMP
Stimulates R
C R
Protein kinase
C R C Active
C Protein kinase A
 Androgenic hormones

• DHEA – dehydroepiandrosteron
• androstenedion
• testosteron
– testosterone is a precursor of estradiol
• effects:
– anabolic
– development of the secondary sexual signs
– distribution of hair
– voice
– sexual behavior - libido
 Disorders of adrenal cortex
A) Hypo function of adrenal cortex - ''ADDISION' DISEASE''

Addison's disease is an autoimmune disease in which antibodies are formed

against adrenal cortex causing its damage and atrophy.
Manifestations:
 Hypotension: Due to Aldosterone deficiency Na+ and water loss in
urine Hypovolemia decreased arterial blood pressure.
 Hyperkalemia (i.e. increased Blood K+ level) due to Aldosterone deficiency
diminished K+ excretion in urine
 Hypoglycemia. (i.e. decreased blood glucose level) due to Cortisol deficiency
 Asthenia (i.e. generalized muscle weakness) due to tissue hypoxia,
Hyperkalemia and hypoglycemia.
 Resistance to stress is decreased.
 Hyper pigmentation: Bronze skin pigmentation especially occurs in the face,
groins, axilla, nipples, and exposed area to sun light and scars as umbilicus.
 Loss of appetite (anorexia), vomiting and diarrhea.
 Sexual disturbances; e.g. amenorrhea in females.
Treatment:
 Adrenocortical hormones: Aldosterone and Cortisol are given.
 Diet rich in NaCl and glucose but poor in K+.
Acute adrenal crisis :

• hypotension, shock

• febris (e.c. infection, hypoadrenalism)

• dehidration, anorexia, nausea, vomitus

• generalized weakness, apathy, confusion, coma

• Hypoglycemia, hyponatremia, hyperkalemia

Acute adrenal crisis :

Diagnosis : based on strongly suspicious

withdrawl of GCC
sepsis
bleeding

Diagnostic : glucose , Na+ , K+

Therapy
Acute :

- Hydrocortison 100 mg iv  100 mg infusion/8-h

- Dextrose 5% or NaCl 0.9%

Chronic :
- GCC & mineralocorticoid substitution
- Hydrocortison 20-25 mg/day or
Prednison/prednisolon in equivalent dose

2/3 – 3/4 dose : morning

1/3 – 1/4 dose : evening
 B- Hyper function of adrenal cortex
''Cushing's syndrome''
It is due to excessive secretion or
administration of Glucocorticoids
(Cortisol and corticosterone)
Manifestations:
1- Increased protein catabolism; this leads to:
 Muscle wasting and weakness.
 Thin skin, hair and subcutaneous tissues.
 Osteoporosis; loss of bone mass due to
decreased protein content with bone
demineralization leading to:
o Deformity and fractures of bone
o Collapse of vertebrae leading to Kyphosis
(i.e. arching of the back).
2- Abnormal fat distribution; fat is deposited
in:
 Face becomes rounded (moon face)
 Supra-clavicle region and back of the
neck and inter-scapular region.
 Trunk and abdominal wall (trunk obesity);
while extremities are thin (Buffalo hump
appearance) .
CUSHING ‘S SYNDROME
Hypercortisolism
Hypercortisolism (cortisol
(cortisol ))

Cushing
Cushing disease
disease :: primary
primary hypercortisolism
hypercortisolism
(from
(from pituitary)
pituitary)

Etiology :
-- Exogen
Exogen :: administration
administration of of supraphysiologic
supraphysiologic doses
doses of
of CS
CS
in
in long
long term
term
-- Endogen
Endogen :: -- pituitary
pituitary tumor
tumor (( 60-70%)
60-70%)
-- adrenal
adrenal tumor
tumor (20%)
(20%)
-- nonendocrine
nonendocrine tumors
tumors ACTH-like
ACTH-like substance
substance ::
>> Oat cell Ca (lung tumor)
>> Carcinoid bronchial
bronchial adenoma
adenoma
>> Prostat / Ovarium Ca
Ca
>> Pancreas Ca
Cushing Syndrome
Cushing’s disease
Diagnosis :
Clinical app : habitus, striae, osteoporosis, hypertension

1. Exogenous : history of usage of CS drugs

blood cortisol & ACTH at 8.0 a.m
2. Endogenous : 2 steps
a) screening test : dexamethasone test
1 mg of dexamethasone at 10 p.m (po)
morning at 8 a.m : blood cortisol level
Normal response : cortisol < 5 µg/dl
Cushing’s disease : no cortisol suppression
Diagnosis :
Liddle
Liddle test
test ::
0.5
0.5 mgmg (po)
(po) dexamethasone
dexamethasone every
every 6-h
6-h intervals
intervals –– 48
48 hh
24-h
24-h urine
urine samples
samples for
for 17-OCHS
17-OCHS
(before
(before and
and during
during dexamethasone
dexamethasone administration)
administration)

Normal
Normal :: urine
urine 17-OCHS
17-OCHS
Cushing’s
Cushing’s dis:
dis: fail
fail to
to suppress
suppress

b) Definitive test
1.
1. Cortisol
Cortisol &
& ACTH
ACTH level
level without
without dexamethasone
dexamethasone adm
adm
2.
2. Metyrapone
Metyrapone test
test
Diagnosis :

Radiologic diagnosis :
1. X- ray : sella turcica
2. Adrenal angiography & venography :
uni/bilateral ?
3. Scanning

Treatment :
1. Surgery
2. Pituitary irradiation
3. Drugs: metyrapone ( inhibits 11-β hydroxylase )
- pre-operative
- inoperable adrenal Ca
- ectopic tumor with unknown sites or has
already metastated
 Cushing’s
Syndrome

“moon face”

striae
ADRENAL MEDULLA
AND
CATECHOLAMINES
 Adrenal medulla

a) The adrenal medulla secretes

Catecholamines: Adrenaline or
Epinephrine (80%) and
noradrenaline or
Norepinephrine (20%)
hormones.
b) Adreno-medullary hormones
help the activity of sympathetic
system when generalized
sympathetic stimulation occurs
(stress response or flight and
fight response)
Adrenal Medulla

Histology :
chromafin cells, contain granules (catecholamine)

Function :
tyrosine CATECHOLAMINE

- adrenalin
- noradrenalin

* Paraganglia cells
* CNS
* End of otonomic nerves
 tyrosine
tyrosine

DOPA
DOPA (dihydroxyphenilalanine)
(dihydroxyphenilalanine)

dopamine
dopamine
PEMT
PEMT
norepinephrine
norepinephrine epinephrine
epinephrine
COMT
COMT MAO
MAO MAO COMT
COMT
MAO

normetanephrine
normetanephrine dihydroxy
dihydroxy mandelic
mandelic acid
acid metanephrine
metanephrine
COMT
COMT
MAO
MAO MAO
MAO
vanilly
vanilly mandelic
mandelic acid
acid

urine
MAO
MAO :: Mono
Mono AmineOxidase
AmineOxidase
COMT
COMT :: catechol-O-methyl-transferase
catechol-O-methyl-transferase
PEMT
PEMT :: phenyl
phenyl ethanol
ethanol amine-N-methyl
amine-N-methyl transferase
transferase
 Effects :

2 receptors :  and β (β1, β2)

peripheral vasoconstriction
-receptor midriasis
hyperhydrosis
noradrenalin

vasodilatation
bronchodilatation
β-receptor cardiac : inotrophic &
chronotrophic effect
adrenalin
gastric motility
Autonomic Nervous System (ANS)
• Involuntary or visceral nervous system
• Regulates the activity of:
– Cardiac Muscle (Heart)
– Smooth Muscle ( In Hollow Organs)
• Blood Vessels
• Digestive System
• Bronchioles
• Sphincters
– Glands
• Adrenal
• Digestive glands
ANS Divisions
o Sympathetic: o Parasympathetic:
o “Fight or Flight” o “Rest & Digest”
o Activated during o Reduces energy use
emergencies, exercise o Promotes:
or vigorous physical  digestion of food
activity
 storage of energy
o Revs up body to
respond to situations  elimination of
that upset homeostasis wastes
 homeostasis
Mosby items and derived items © 2006 by Mosby, Inc.
Somatic versus Autonomic Pathways

ANS = 2 neurons from CNS to effectors

• presynaptic neuron cell body in CNS
• postsynaptic neuron cell body in peripheral ganglion 15-68
 Sympathetic - Origin
• Thoracolumbar
• Nerve fibers originate between T1 & L2
Sympathetic Nervous System
pathways of preganglionic fibers
1.enter ganglia and synapse on
postganglionic cell
2.travel to higher or lower ganglia and
synapse
3.pass through chain without synapsing to
reach collateral ganglia via splanchnic
nerves

15-70
Preganglionic Pathways

15-71
Efferent Pathways

15-72
 Adrenal Medulla Glands
• Medulla (inner core)
– a modified sympathetic ganglion
• stimulated by preganglionic sympathetic neurons
– secretes neurotransmitters (hormones) into blood
• catecholamines (80% epinephrine and 20% norepinephrine)
• Sympathoadrenal system is the closely related
functioning adrenal medulla and symphathetic
nervous system

15-73
Ganglia and Abdominal Aortic Plexus

15-74
 Parasympathetic - Origin
• Craniosacral
• Nerve fibers emerge from brain & sacrum
 Parasympathetic Nervous
System
• Pathways of preganglionic fibers
– cranial nerves III, VII, IX and X
– arising from sacral spinal cord
• pelvic splanchnic nerves and inferior
hypogastric plexus
• Terminal ganglia in/near target organs
– long preganglionic, short postganglionic
fibers
15-76
Efferent Pathways

15-77
Parasympathetic Cranial
Nerves
• Oculomotor nerve (III)
– narrows pupil and focuses lens
• Facial nerve (VII)
– tear, nasal and salivary glands
• Glossopharyngeal (IX)
– parotid salivary gland
• Vagus nerve (X)
– viscera as far as proximal half
of colon
– Cardiac, pulmonary, and
esophageal plexus

15-78
 Parasympathetic
Innervation of Visceral
Targets
• Ganglia close to or on target organs
• Preganglionic neurons - long
• Post ganglionic neurons - short
 Parasympathetic
Neurotransmitters
• Preganglionic neurons release
acetylcholine = Cholinergic
 Parasympathetic
Neurotransmitters
• Postganglionic neurons release
acetylcholine = Cholinergic
 Cholinergic Receptors
• Found on skeletal muscle cells
regulated by motor neurons.

Motor Neuron
 Cholinergic Receptors
• Found on dendrites & cell bodies of
postganglionic neurons of both
sympathetic and parasympathetic
divisions of ANS.

• Found on parasympathetic target

organs.
 Cholinergic Receptor
Types
• Muscarinic:
Nicotinic:
• On all
skeletal
targetmuscle
organscells
of
• parasympathetic
On postganglionic dendrites & cell
• bodies
May excite
in both
or decrease
sympathetic
activity
&
parasympathetic
depending on target
• Almost always excite
 Muscarinic Receptor
Effects
• Cardiac Muscle - Slows heart rate
and strength of contraction
• Digestive System - Increases
digestive activity including
secretions & peristalsis.
• Increases flow of blood to liver,
pancreas & digestive organs by
vasodilation of appropriate vessels.
• Eye - Causes constriction of Iris
 Sympathetic
Innervation of Visceral Targets
• Short, lightly myelinated preganglionic
neurons
• Long, unmyelinated postganglionic neurons
o Ganglia close to spinal cord

Spinal
Cord
Mosby items and derived items © 2006 by Mosby, Inc.
 Sympathetic
Neurotransmitters
• Preganglionic neurons -
– Cholinergic = ( release acetylcholine )
 Sympathetic Neurotransmitters
• Postganglionic neurons:
– release norepinepherine at target organs
– ie. Adrenergic
• Adrenal medulla:
– releases epinepherine & norepinepherine into
blood
– ie. Adrenergic

Mosby items and derived items © 2006 by Mosby, Inc.

 Adrenergic Receptors
o Located only on sympathetic target organs

• Respond only to norepinepherine released

by postganglionic neurons (precise effects)
or
• Epinepherine & norepinepherine released
by adrenal medulla into blood (general
effects)
Mosby items and derived items © 2006 by Mosby, Inc.
Epinephine: 1, 2, b1, b2
Norepinephine: 1, 2, b1
Dopamin & Dobutamin: b1
 Action of Catecholamines
Catecholamine act on:
I. Metabolism: Adrenaline stimulates basal metabolic rate, liver
glycogenolysis, muscle glycogenolysis and lipolysis.
II. The heart: Catecholamine stimulates all cardiac properties and dilates
coronary vessels. So, it produces:
 Increased heart rate (tachycardia), increased force of contraction, increased
excitability & enhanced conductivity, increased metabolism and O2
consumption and coronary vasodilatation.
III- On blood vessels & blood pressure:
o Noradrenalin causes generalized vasoconstriction increase in
the peripheral resistance increase of blood pressure with
concomitant decrease in cardiac output.
o Adrenaline causes vasoconstriction of skin, renal and splanchnic blood
vessels whilst vasodilatation occurs in skeletal muscles blood vessels.
Cardiac output is increased.
IV-Central nervous system: Catecholamine increases the excitabilities of CNS and
shortens the response time. Adrenaline increases the alertness, awareness
and mental activity.
V- Respiration: Catecholamine increases the rate and depth of respiration.
VII- Skin: adrenaline causes pallor of the skin due to cutaneous vasoconstriction
 tyrosine
tyrosine

DOPA
DOPA (dihydroxyphenilalanine)
(dihydroxyphenilalanine)

dopamine
dopamine
PEMT
PEMT
norepinephrine
norepinephrine epinephrine
epinephrine
COMT
COMT MAO
MAO MAO COMT
COMT
MAO

normetanephrine dihydroxy
dihydroxy mandelic
mandelic acid
acid metanephrine
metanephrine
COMT
COMT
MAO
MAO MAO
MAO
vanilly
vanilly mandelic
mandelic acid
acid

urine
urine
MAO
MAO :: Mono
Mono AmineOxidase
AmineOxidase
COMT
COMT :: catechol-O-methyl-transferase
catechol-O-methyl-transferase
PEMT
PEMT :: phenyl
phenyl ethanol
ethanol amine-N-methyl
amine-N-methyl transferase
transferase
Phaeochromocytoma

Tumor of chromaffin cells cathecholamine

 1% of hypertensive pts
 curable
 tumors : adrenal medulla
paraganglia along aorta abdominal
(zuckerkandl)
vesica
vesica urinaria,
urinaria, mediatinum
mediatinum
Clinical manifestations :

Depend on :
• type of catecholamine which is predominant
(adrenalin or noradrenalin)

Noradrenalin
Noradrenalin ::
Adrenalin
Adrenalin ::
-- Hypertension
Hypertension -- Palpitation
Palpitation
-- Headache
Headache -- Chest
Chest pain
pain
-- Sweating
Sweating -- Tremor
Tremor
-- Pallor
Pallor -- Flushing
Flushing
-- Nausea
Nausea
• secretion : continous or paroxysmal

Paroxysmal
Paroxysmal :: Precipitating
Precipitating factors
factors ::
 episodic
 episodic -- exercise
exercise
-- stress
stress
(mnts
(mnts –– hours)
hours)
-- eating
eating
 << 11 hour
 hour -- abdominal
abdominal palpation
palpation
Diagnosis :
- Definitive : plasma catecholamine
- 24-hours urine VMA

Teraphy : - operative  risky !!

- medicamentosa : α-blocker ; β-blocker

Pre-op : stress  catecholamine

crisis hypertension  Heart failure
Intra-op : acute vasodilation  relative hypovolemic shock
Pheochromocytoma - Screen
 Best detected during or immediately
after episodes
Sensitivity Specificity
Plasma free 99% 89%
metanephrine
>.66nmol/L

24hr urine 77% (95%) 93% (96%)

metanephrine
(>3.7nmol/d)

24 urine VMA 64% 95%

Lenders, et al. JAMA 2002 Mar 20;287(11):1427-34

 Adrenal Medulla
• L-Tyrosine converted to
• L-DOPA converted to
• Dopamine converted to
• L-Norepinephine converted to
• L-Epinephrine
• Degrades to VMA, metanephrine,
normetanephrine
TERIMAKASIH