Structure
1. Located
at the top of the kidneys, fitting like caps.
2. Made
up of two portions:
a. Adrenal
cortex – composed of endocrine tissue
b. Adrenal
medulla – composed of neurosecreting tissue (catecholamines); inner portion.
THE ADRENAL
CORTEX
Layers of secretory cells:
1. Zona
glomerulosa – outermost layer, directly under the outer connective tissue
capsule of the adrenal gland; secretes mineralocorticoid.
2. Zona
fasciculate – middle layer; secretes glucocorticoid.
3. Zona
reticularis – inner layer; secretes small amounts of glucocorticoid and
gonadocorticoids.
The corticosteroids
1.
Mineralocorticoids
a. Has
an important role in the regulatory process of mineral salts in the body.
b. Aldosterone
(1) Only
physiologically important mineralocorticoid in human; primary function is
maintenance of sodium homeostasis in the blood by increasing sodium
reabsorption in the kidney.
(2) Aldosterone
also increases water retention and promotes the loss of potassium and hydrogen
ions.
(3) Aldosterone
secretion is controlled by the renin–angiotensin mechanism and by blood
potassium concentration.
Regulation of
secretion of aldosterone
(1) The
initial step of aldosterone synthesis (cholesterol to pregnenolone) is under
control of ACTH but the steps after pregnenolone synthesis are controlled by
the renin–angiotensin system and the fluid volume.
(2) If
the sodium concentration and or plasma volume decreases, the proteolytic enzyme
renin is released from the juxtaglomerular cells of the nephron into the
plasma.
(3) It
has been hypothesized that baroceptors in the juxtaglomerular cells respond to
changes in blood pressure. If the baroceptors are stretched because of an
increase in blood pressure, renin secretion is inhibited, whereas a decrease in
blood pressure stimulates renin secretions.
(4) A
circulating protein called angiotensinogen is cleaved by the renin to form
angiotensin I.
(5) Angiotensin
I is modified by converting enzymes in the plasma and the lung tissue to become
angiotensin II.
(6) Angiotensinogen
II stimulates the cells in the adrenal cortex to synthesize and release
aldosterone.
(7) In
addition, angiotensin II causes constriction of the peripheral arteries,
resulting in an increase in the blood pressure and an increased filtration rate
in the kidney.
Assay
methodology
(1) RIA,
available in kits (for renin and aldosterone)
(2) For
aldosterone determination, the position of the patient either lying down
(supine) or upright must be noted for proper interpretation of results.
Normal values: Upright = 5 – 30 ng/dl
Supine = 3 –
10 ng/dl
(3) The
activity of renin is measured rather than the concentration of the enzyme
itself and is based on the amount of angiotensin I produced from
angiotensinogen.
Normal values: Upright = 0.1 – 3.1 ng/hour/ml
Supine = 1.6
– 7.4 ng/hour/ml
2.
Glucocorticoids
a. Main
glucocorticoid secreted by the zona fasciculata is cortisol, cortisone and
corticosterone with cortisol the only one secreted in significant quantities.
b. Affect
every cell in the body.
c. They
are protein–mobilizing, gluconeogenic and hyperglycemic.
d. Tend
to cause a shift from carbohydrate catabolism to lipid catabolism as an enzyme
source.
e. Essential
for maintaining normal blood pressure by aiding norepinephrine and epinephrine
to have the full effect, causing vasocontriction.
f.
High blood concentration causes
eosinopenia and marked atrophy in lymphatic tissues.
g. Act
with epinephrine to bring about normal recovery from injury produced by
inflammatory agents.
h. Secretion
increases in response to stress.
i.
Except during stress response,
secretion is mainly controlled by a negative feedback mechanism involving ACTH
from the adenohypophysis.
Regulation of
secretion of cortisol
a. ACTH
from the anterior pituitary is responsible for stimulating the release and synthesis
of glucocorticoids from the zona fasciculata. The conversion of cholesterol to
pregnenolone (the rate–limiting step) is under the control of ACTH as well as
subsequent reaction that produce cortisol.
b. Ninety
percent of cortisol released into the blood circulates attached to CBG or
albumin and has a half life of approximately 90 minutes.
c. The
secretion of cortisol is diurnal and is associated with a
person’s sleep–wake cycle. A peak level of cortisol is usually observed
between 6 and 8 am and a low level between 6pm and 12am.
The concentration of cortisol in the plasma at 8pm is approximately 50% of the
level at 8am.
d. Changes
in sleeping patterns or stress levels cause alterations in the secretion of
ACTH and cortisol.
e. Cortisol
stimulates both gluconeogenesis and glycogenesis in the liver, resulting in
increases in the plasma glucose.
(Click
here for discussion about gluconeogenesis under Carbohydrate)
(Click
here for discussion about Liver Function Test)
f.
The stimulation of gluconeogenesis
in the liver occurs in the fasting state and in conjunction with cortisol’s
inhibition of glucose uptake in peripheral tissues, causes the increase in
plasma glucose.
g. Since
many amino acids are being used for gluconeogenesis in the liver, muscle uptake
of amino acids is inhibited and protein catabolism increases, usually causing a
loss of muscle tissue.
h. Excess
cortisol has been shown to decrease the amount of calcium that is absorbed from
the intestine, initiating a decrease in plasma calcium. Plasma calcium concentrations
are maintained by the body by removing calcium from storage in the bone tissue.
i.
Cortisol will stimulate
lipolysis in adipose tissue so that the plasma concentration of glycerol and
free fatty acids will increase.
j.
Cortisol in high concentrations
will cause both anti–inflammatory and immunosuppressive actions. These actions of
cortisol make it a valuable therapeutic agent in some types of diseases such as
rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis.
GENERAL
METHODS EMPLOYED IN STERIOD DETERMINATION
A.
Hydrolysis
1.
Acid
hydrolysis (mineral acid method) – portion of a 24 hour urine sample is
boiled under reflux in a specific length of time (10–60 minutes). Except for
acid labile hormones, this method is preferred because of simplicity, speed and
completeness of reaction.
2.
Enzymatic hydrolysis
a. A
portion of a 24 hour urine specimen is adjusted with buffer to the optimal pH
of the enzyme employed.
b. An
adequate amount of the respective enzyme (beta–glucosidase to hydrolyze
glucosidunates and sulfatase to hydrolyze sulfate conjugates) are added and the
test sample incubated for 18–76 hours at 37oC).
c. This
method requires special attention regarding optimal concentration of enzyme,
optimal pH of the enzyme, temperature and duration of incubation.
d. The
method is employed when the steroids are labile in strong acid solution (e.g.
pregnanetriol, corticosteroid)
B.
Extraction
Organic
solvents are used for extraction. Selection of solvents is based on polarity of
the steroids.
Steroids with
one or two oxygen (like androgens and estrogens) are low polarity and solvent
used are chloroform, dichlormethane or ethyl acetate.
C.
Purification
This is
necessary because a large number of urinary pigment chromogenic substances and
other non–specific materials are invariable extracted along with the steroid
and they will interfere in the final estimation of the steroid if they are not
removed.
Strongly acid
component migrate into aqueous layer and discarded. Neutral and phenolic
steroids can be done in the same way. Phenolic steroids (estrogen) being acid
in nature are readily extracted with an aqueous solution of hydroxide. After
lowering the pH of the alkaline solution, estrogens are re – extracted with a
suitable solvent like diethyl ether and are processed further for final
estimation.
D.
Estimation
1. Colorimetric
method
2. Flurometric
method
3. Gas
chromatography
Urinary metabolites of cortisol
quantitated
1. 17–hydroxycorticosteroids
– have hydroxyl groups at C–21 and C–17 and a keto group at C–20; this
configuration is known as dihydroxyacetone side chain. These
compounds are measured using the Porter–Silber reaction.
2. 17–ketogenic
steroids group as:
Group I : cortisol,
cortisone, 11–deoxycortisol, tetrahydro S
Group II : cortols
and cortolones
Group III : pregnanetriol
and 11–oxygenated derivatives
Group IV : 17–hydroxyprogesterone,
17–hydroxypregnenolone
·
These compounds are measured
using the Zimmerman reaction
Interference
in 17–ketosteroid determination
a. Cortisol
b. Dexamethasone
c. Equanil
d. Librium
e. Quinine
f.
Seconal
g. Thorazine
h. Serpasil
i.
Nodular
j.
Paraldehyde
The Porter–Silber reaction
17–hydroxycorticosteroids and
phenylhydrazine are incubated at 60oC for 30 minutes. A
characteristic yellow pigment is formed that can be measured in a
spectrophotometer at 410 nm.
The Zimmerman reaction (Appleby
method)
1. Treatment
of sodium bismuthate to break the 17–hydroxyl bond and replace it with a
ketogroup at position 17.
2. The
17–ketosteroid is then quantitated by producing a color reaction with
dinitrobenzene in the presence of alcohol and potassium hydroxide.
3. A
reddish purple pigment is formed and readings are taken in a spectrophotometer
at 480, 520 and 580 nm.
Biosynthesis of Adrenal Hormone
The biosynthesis of the adrenal
steroids is a multienzyme (cytochrome P–450 oxygenase) process that takes place
in the cytoplasm and mitochondria of the cortex endocrine cells. Synthesis of
the various steroid hormones start at the mitochondria with the conversion of
cholesterol, primarily from the plasma lipoprotein, to pregnenolone. The
pregnenolone must be transported out of the mitochondria and to the various
intracellular sites for the process of hormone synthesis to continue.
In addition, this is the rate–limiting
step in the synthesis of adrenal steroids and is primarily under the control of
adrenocorticotropic hormone (ACTH). At this point, the pathways diverge to
produce the different hormone. The individual layers of the adrenal cortex
contain the enzyme necessary for each of the respective hormones produced
there. For example, the zona glomerulosa has the enzyme 18– hydroxysteroid
dehydrogenase that is necessary for the production of aldosterone but lacks the
enzyme 11–beta–hydroxylase necessary for cortisol synthesis. This layer also
lacks the enzyme 17–alpha–hydroxylase that is required for the production of
androgens.
Metabolism of adrenal hormone
The major site of metabolism for the
steroid hormone is the liver. The rate of metabolism by the liver is dependent
on whether the hormone is bound to a protein carrier. A higher percentage of
aldosterone is not protein bound is removed from circulation and metabolized by
the liver more rapidly than cortisol, which is mostly bound to a protein
carrier (transcortin, also called corticosteroid–binding protein, CBG).
Most steroids excreted in urine must
be conjugated by the liver to either glucuronic acid or sulfates to form
soluble compounds. The metabolism of cortisol begins in the liver with a delta
reductase enzyme and dehydrocortisol is produced. Dehydrocortisol is not
excreted in urine and is further metabolized by 3–alpha– hydroxysteroid
dehydrogenase. The metabolites formed from this reaction are the major (50%)
excretory compounds of cortisol (tetrahydrocortisol, tetrahydrocortisone).
Approximately 30% of urinary metabolites of cortisol are cortrol and cortolone
and are formed by the hydrogenation of the C–20 ketone group. In normal
patients, very little urinary free cortisol is found. Conversely, relatively
large amounts of urinary free cortisol are seen in patients with Cushing’s
syndrome.
Clinical significance of
adrenal cortex function
1.
Primary
Mineralocorticoid Excess
a. Primary
Aldosteronism
2.
Syndrome with
Deoxycorticosterone (DOC) Excess
a. 17–alpha–hydroxylase
deficiency
b. 11–beta–hydroxylase
deficiency
c. Androgen–estrogen–producing
adrenal tumors
d. Syndrome
of Primary Cortisol Resistance
3.
Syndrome with
Secondary Mineralocorticoid Excess
a. Hypertension
4.
Syndrome of
Glucocorticoid Excess and Hypertension
a. Cushing’s
syndrome
b. Other
hypertensive syndromes with pseudorhyperaldosteronism
(1) Secondary
Mineralocorticoid Deficiency
(2) 11–beta–hydroxysteroid
dehydrogenase deficiency
(3) Chronic
ingestion of licorice
(4) Liddle’s
syndrome
(5) Arnold–Healy–Gordon
syndrome
THE ADRENAL
MEDULLA
Structure
1. Located
at the middle portion of the adrenal gland
2. Chromaffin
cells or pheochromocyte
a. Large,
ovoid, columnar cells arranged in clumps or cords around blood vessels.
b. Their
granules turn brown when stained with chromic acid due to the oxidation of
epinephrine and norepinephrine to melanin.
c. These
cells have large nuclei and well–developed Golgi complex.
d. They
contain large numbers of vesicles or granules containing catecholamine.
Vesicles containing norepinephrine are darker than those containing
epinephrine.
e. The
reason for the high production of epinephrine is the presence of the enzyme
phenylethanolamine–N–methyltransferase (PNMT).
Schema of
embryonic development of adrenergic cells
Hormones
of the adrenal medulla
Catecholamine is a collective term
used to describe the hormones of the adrenal medulla. The adrenal medulla is a
highly innervated tissue with many neurons that appear to be in direct contact
with chromaffin cells. Catecholamine hormone release can be stimulated by the
action of these neurons.
1.
Dopamine
a. Appear
in highest concentration in the central nervous system, where if functions as a
neurotransmitter.
b. In
hypothalamus, it helps to control the synthesis of prolactin from the
pituitary. When dopamine is present, prolactin is inhibited and when dopamine
is absent, prolactin is freely secreted.
c. The
final metabolite of dopamine is homovanillic acid (HVA).
2.
Norepinephrine
a. The
highest concentration of norepinephrine is found in the brain (CNS) and to a
lesser degree in the sympathetic nervous system (SNS) where it functions as
neurotransmitter.
b. Acting
primarily through the alpha adrenergic receptors, norepinephrine can cause many
varied responses. These responses include such physiologic actions as
vasoconstriction of the small vessels in the skin or relaxation of the smooth
muscle of the gastrointestinal tract.
3.
Epinephrine
a. The
major catecholamine produced by the chromaffin cells of the adrenal medulla.
b. It
is often called the “flight or fight” hormone since it is released in response
to physiologic (injuries) or psychological (stress, anxiety, threats).
c. Epinephrine
secretion causes increased heart rate, blood pressure, respiration and
metabolic rate.
d. In
addition, it stimulates glucogenolysis in the liver and skeletal muscle that
leads to increase in the plasma glucose level.
Synthesis of catecholamine
The synthesis
of catecholamine can be measured by the following procedures
1.
Conversion of
tyrosine to dopa
The
catecholamines are synthesized from tyrosine, which may be derived from
ingested food or synthesized from phenylalanine in the liver. Tyrosine circulates
at a concentration of 1–1.5 mg/dl of blood. It enters neurons and chromaffin
cells by an active transport mechanism and is converted to
dihydroxyphenylalanine (dopa). The reaction is catalyzed by tyrosine
hydroxylase, which is transported via axonomal flow to the nerve terminal.
2.
Conversion of
dopa to dopamine
This is
through the action of the enzyme dopa decarboxylase. This enzyme
is found in all tissues, with the highest concentrations in the liver, kidney,
brain and vas deferens. Competitive inhibitors of dopa decarboxylase such as
methyldopa are converted to substances that are then stored in granules in the
nerve cell and released in place of norepinephrine.
3.
Conversion of
dopamine to norepinephrine
This is
through the action of the enzyme dopamine β–hydroxylase. This
enzyme when newly synthesized is incorporated directly into storage vesicles
that take up, synthesize and store catecholamines. The membranes of these
vesicles contain dopamine β–hydroxylase, ATPase, cytochrome P–561: NADH
reductase. Dopamine β–hydroxylase is also found within the granules and is
released with norepinephrine during secretion. Inhibitors of the enzyme, such
as disulfuramic and picolinic acid, have no clinical importance.
4.
Conversion of
norepinephrine to epinephrine
PNMT catalyzes
the N–methylation of norepinephrine to epinephrine, using 8–adenosylmethionine
as a methyl donor. It is found only in the adrenal medulla and in a few neurons
in the central nervous system. The enzyme is found in the cytosol.
Norepinephrine leaves the granule and after methylation reenters different
granules. This enzyme is induced by the high levels of glucocorticoids found in
the adrenal medulla. The conversion of dopamine to epinine is catalyzed by a
non–specific N–methyltransferase
Metabolism of catecholamines
Catecholamines that are secreted into
the plasma have a short half–life of about 1 to 2 minutes. They are rapidly
remove from the circulation by the liver and kidneys or taken up by sympathetic
neurons.
Two enzyme systems are responsible for
the breakdown or inactivation of the catecholamine hormones. Monoamine
oxidase (MAO) deaminates the catecholamines and is present in many
tissues throughout the body.
The second enzyme, catechol–o–methyl–transferase
(COMT), methylates a hydroxyl group on the aromatic ring structure of
the catecholamine molecule. COMT is found in highest concentration in kidneys
and liver. The methylation reaction of this enzyme produces metaneprine from
epinephrine and normetanephrine from norepinephrine.
Both metanephrine and normetanephrine
can be conjugated with sulfate or glucuronide and excreted in the urine. The
final metabolite of both epinephrine and norepinephrine is vanillylmandelic
acid (VMA).
Receptors
The action of the catecholamine
hormones is mediated through adrenergic receptors. There are two alpha
receptors and two beta receptors. These receptors are found throughout the body
in most tissues. Some tissues have both alpha and beta receptors present,
whereas other tissues may have only one type.
Both epinephrine and norepinephrine
interact with these receptors, although the receptor affinity for the two
hormones may be different. The alpha–1 receptor uses calcium and phosphatidyl
inositol for its second messengers. The alpha–2, beta–1 and beta 2–receptors
are cAMP as their second messenger.
Regulation of secretion of
catecholamines
Adrenal medullary catecholamine
secretion is increased by exercise, angina pectoris, myocardial infarction,
hemorrhage, ether anesthesia, surgery, hypoglycemia, anoxia and asphyxia and
many other stressful stimuli.
The rate of secretion of epinephrine
increases more than that of norepinephrine in the presence of hypoglycemia and
most other stimuli. However, anoxia and asphyxia produce a greater increase in
adrenal medullary release of norepinephrine than is observed with other
stimuli.
Secretion of the adrenal medullary
hormones is mediated by the release of acetylcholine from terminals of preganglionic
fibers. The resulting depolarization of the axonal membrane triggers an influx
of calcium ions. The contents of the storage vesicles, including the
chromograms (storehouse of catecholamines) and soluble dopamine
beta–hydroxylase, are released by exocytosis by the calcium ion increase.
Membrane bound dopamine beta–hydroxylase is not released.
Tyramine, however, releases
norepinephrine primarily from the free store in the cytosol. Cocaine and
monoamine oxidase inhibitors inhibit the effect of tyramine but do not affect
the release of catecholamines by nervous stimulation. The rate of release in
response to nerve stimulation is increased or decreased by a wide variety of
neurotransmitter acting at specific receptors on the presynaptic neuron. Norepinephrine
has an important role in modulating its own release by activating the alpha
receptors on the presynaptic membrane.
Alpha–2 receptor antagonists inhibit
this reaction. Conversely, presynaptic beta receptors enhance norepinephrine
release, whereas beta receptor blockers increase it. The accumulation of excess
catecholamine that is not in the storage granules is prevented by the presence
of intraneuronal monoamine oxidase.
Laboratory evaluation of
adrenomedullary function
1.
Dopamine
a. Assay
methodology: radioenzymatic kit method using plasma
Utilizes the enzyme
COMT to transfer a H–methyl group to the catecholamine. All catecholamine
present in the sample are H– methylated. The catecholamines is extracted from
the sample and are separated by thin layer chromatography. The amount of
radioactivity in each of the chromatography spots can be measured and the
individual catecholamine quantitated.
Normal value: 0 – 83 pg/dl
Precaution in
specimen collection
(1) Specimen
should be collected by catheterization since venipuncture tend to increase
catecholamine
(2) The
blood drawing tubes should contain sodium thiosulfate and EDTA.
(3) Blood
samples must be placed on ice immediately after drawing
(4) The
blood should be separated with a refrigerated centrifuge as soon as possible
after drawing and the plasma frozen at –70oC until the analysis is
performed.
b.
Urine HVA
using GC or HPLC
Precaution in
specimen collection
(1) A
24 hours specimen is collected and 10 ml of concentrated HCl is added as
preservative.
(2) During
the collection time, the urine container should be kept in refrigerator.
(3) Once
the 24 hour urine specimen is returned to the laboratory, the toal volume
should be recorded and the specimen is aliquoted.
(4) The
pH of all aliquots should be adjusted to about pH 3 to 4 using 6M HCl.
Normal values: <15
mg/24 hours
2.
Norepinephrine
and epinephrine
a.
Using plasma
sample
(1) The
radioenzymatic method described previously for dopamine using COMT and H–methylation
of the catecholamine followed by TLC can also be used here.
Normal values: Epinephrine = 0 – 62 pg/ml
Norepinephrine
= 111 – 603 pg/ml
(2) Ethylenediamine
(EDA) Fluorometric method
(a) Extracting
the catecholamine from the plasma first with an alumina column followed by an
Amberlite CG–50 column.
(b) EDA
is added to the collected eluate, where it combines with the catecholamine
(c) Three
fluorescent products are obtained from norepinephrine and one from the
epinephrine.
(d) These
products are measured in a fluorometer at two different wavelengths (emission
510 and 580 nm, activation 420) and concentrations of the hormones are
calculated.
Normal values:
Epinephrine
= 140 – 300 pg/ml
Norepinephrine
= 360 – 800 pg/ml
Assay
interference: Penicillin, coffee, tea
b.
Using urine
sample
(1) Urine
vanillylmandelic acid and colorimetric method
(a) Hydrolysis
with HCl to destroy conjugates is the initial step in the process.
(b) Solvent
extraction with ethyl acetate separates the VMA into the organic layer.
(c) Further
purification of the mixture is accomplished by reextracting the VMA into an
aqueous potassium carbonate solution.
(d) Treatment
with sodium metaperiodate oxidizes VMA to vanillin which can be quantitated
spectrophotometrically.
Normal values: 2 – 7 mg/24 hours
Interference
in the determination
(a)
Falsely
decreased values
pH above 3
decomposes VMA, salicylates, clofibrate and L–dopa, clonidine, disulfram,
hydrazine derivatives, imipramine, MAO inhibitors, morphine, phenothiazines and
some radiography agents.
(b) Falsely
elevated values
Bananas,
coffee, tea, vanilla, chocolates, salicylates, disulfram, nalidixic acid,
oxytetracycline, pthalein dyes, insulin, isoproterenol, L–dopa, lithium,
reserpine
(2)
Fluorometric
assay
(a) Adjust
the urine pH to alkaline range. Both epinephrine and norepinephrine exist as
neutral compounds at pH values above 8 since the amine groups on these
molecules are not protonated. These forms of molecules then bind to alumina or
resin ion– exchange columns.
(b) After
washing to remove other materials, the catecholamine is eluted with dilute
acid.
(c) Oxidation
with ferricyanide converts the catecholamine to cyclic derivatives. Addition of
trihydroxyindole derivatives to fluorescent forms.
Normal values: Epinephrine
= 0 – 15 ug/24 hours
Norepinephrine
= 0 – 100 ug/24 hours
Dopamine
= 65 – 400 ug/24 hours
Interference
in the assay:
Falsely
elevated values is seen in pH values below about 8.5 will lead to lowered
extraction efficiency, prolonged refrigeration sometimes discolors the sample
causing increased blank values.
(3)
Urine
metanephrine using Pisano method
(a) Hydrolysis
with HCl breaks down all conjugates, allowing more uniform extraction of all
fractions.
(b) The
solution containing the metanephrine mixture is poured onto an ion–exchange
column which loosely binds the metanephrine but allows other components to pass
through and be removed from the reaction mixture.
(c) Elution
with ammonium hydroxide washes the metanephrine off the column.
(d) Conversion
to vanillin is accomplished through periodate oxidation.
Normal values:
Metanephrine
= 74 – 297 ug/24 hours
Normetanephrine
= 105 – 354 ug/24 hours
HVA =
66 – 222 ug/24 hours
Interference
in the assay:
Falsely
elevated values: chlorpromazine, imipramine, phenothiazines, methyldopa,
tetracycline
Clinical significance
1. Increased
catecholamine level is seen in
a. Pheochromocytoma
b. Neuroblastoma
c. Essential
hypertension
d. Hypothyroidism
e. Diabetic
acidosis
f.
Cardiac disease
g. Burns
h. Septicemia
i.
Depression
2. Decreased
catecholamine level is seen in
a. Hyperthyroidism
b. Long–term
diabetes
****** PHEOCHROMOCYTOMA ******
Pheochromocytoma is a rare tumor of
the chromaffin cells. Adrenal chromaffin cell tumors make up about 90% of all
pheochromocytoma. The adrenal tumors may secrete large amounts of epinephrine,
norepinephrine or varying combinations of both. Pheochromocytomas found in
areas other than the adrenal medulla secrete mostly norepinephrine. Most
pheochromocytomas occur in adults and in each sex about equally.
Signs and symptoms
1. Symptoms
during or following paroxysms
a. Headache
b. Sweating
c. Forceful
heartbeat with or without tachycardia
d. Anxiety
or fear of impending death
e. Tremor
f.
Fatigue or exhaustion
g. Nausea
and vomiting
h. Abdominal
or chest pain
i.
Visual disturbances
2. Symptoms
between paroxysm
a. Increased
sweating
b. Cold
hands
c. Weight
loss
d. Constipation
The hypertension seen in connection
with a pheochromocytoma in an alpha receptor effect related to the excess of
norepinephrine produced. The hypertension can be sustained or paroxysmal. The
hypermetabolic features seen in pheochromocytoma resemble those seen in
patients with hyperthyroidism. These include heat intolerance, tremor, weight
loss, palpitations and increase BMR.
In contrast to hyperthyroidism, in
which the patient has hyperthyroidism, patients with pheochromocytoma have
constipation. The increased levels of catecholamine reduced gastrointestinal
motility and increase sphincter tone, which also lead to nausea, abdominal pain
and possibly obstruction.
Pheochromocytoma may be misdiagnosed
since the symptoms are similar to those of several other disorders. When
diagnosed correctly, they are easily treated surgically. If left untreated, the
patient usually dies.
Catecholamine has a tendency to block
insulin release, increase gluconeogenesis and cause fatty acid mobilization.
These actions can elevate serum glucose levels. Some patients have hypokalemia
owing to their diuretic therapy or an elevation of plasma renin and
aldosterone.
****** NEUROBLASTOMA
******
Neuroblastoma is a rare form of
malignant tumor of cells that are neuron precursors found in infants and
children. The primary tumor often is in or near the adrenal gland and is not
found until after the tumor has metastasized to another site such as the liver.
Neuroblastoma secretes sporadic increases in catecholamine hormones. The symptoms
due to the catecholamines may be transient hypertension, sweating, tachycardia
and headaches. Generally, the most persistent symptom is due to tissue damage
from the secondary metastatic sites, that is, the liver or lymph nodes.
Problems encountered in collecting
sample
1. Collection
of a 24 hours specimen from infants and small children.
2. Seventy
to eighty percent of children show increases in urinary VMA, but the increases
vary from just slightly above normal to about ten times the normal level.
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