Gland Cortisol and VMA corticosteroids ACTH ACTH Adrenocorticotropic hormone or corticotropin Is a 39 amino acid peptide hormone MW4500 secreted by the pituitary to regulate the production of steroid hormones by the adrenal cortex ID: 533552
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Slide1
Adrenal Gland
Cortisol and V.M.ASlide2
corticosteroidsSlide3
ACTHACTH (Adrenocorticotropic hormone) or corticotropin.
Is a 39 amino acid
peptide hormone (MW=4500) secreted by the pituitary to regulate the production of steroid hormones by the adrenal cortex.Slide4
ACTH secretion from the anterior pituitary is controlled by both a classical negative feedback control mechanism and CNS-stress mediated control system.Various types of stress or pain perceived in higher levels of the brain modulate secretion of the hypothalamic neurosecretory hormone, corticotropin releasing hormone (CRH), a 41-amino acid peptide. CRH stimulates pituitary ACTH secretion. The
second peptide that modulates ACTH secretion is
vasopressin (AVP).
AVP secretion is also stimulated by stress and acts synergistically with CRH to increase ACTH secretion in the pituitary portal circulation. Slide5Slide6
ACTH increases the synthesis and release of all adrenal sterioids, aldosterone, cortisol and adrenal androgens. It is the principal modulator of cortisol, the most important glucocorticoid in man. As the cortisol level in blood increases,
release of ACTH is inhibited directly at the pituitary level.
Through this same mechanism, decreasing cortisol levels lead to elevated ACTH levels. Slide7
Cortisol
Physiologically effective in
anti-inflammatory
activity and
blood pressure
maintainace
,
cortisol is also involved in
gluconeogensis
.
Cortisol is probably the most measured
analyte
for
evaluating adrenal function
although aldosterone and rennin are also ordered frequently.Slide8Slide9
Primary aldosteronism is being increasingly investigated as a possible secondary cause of hypertension in adults.From the laboratory perspective, this usually involves measuring both aldosterone and renin and calculating aldosterone to renin ratio. Slide10
The determination of ACTH should be performed on EDTA plasma. To assay the specimen in duplicate, 400 μL of EDTA plasma is required.Slide11
Cortisol the glucocorticoid found in the largest concentration in the serum, is the one usually measured to gain information about the functioning of the adrenal cortex.Plasma cortisol has a diurnal variation
, its levels being higher in the morning than in the evening.
Baseline readings are taken in the morning with the
clinet
at rest
.
CortisolSlide12
Increased amounts of ACTH and cortisol are secreted independently of the circadian rthyme in response to physical and psychological stress.Elevated cortisol
levels and lack of diurnal variation have been identified in patients with
cushings
disease
Elevated circulating cortisol levels have also been identified in patients with
adrenal tumorsSlide13
Low cortisol levels are found in primary adrenal inufficiency as adrenal hypoplasia, congenital adrenal hyperplasia or addisson’s disease and in ACTH
defeciency
. Slide14
The timing of the cortisol levels with suppression and stimulation are determined by the procedure of the particular laboratory.Due to the normal circadian variation of cortisol levels distinguishing normal and abnormally low cortisol level =s can be difficult. Therefore, various tests to evaluate the pituitary adrenal axis ACTH-cortisol, including insulin-induced hypoglycemia, short and long term ACTH stimulation
,
CRF stimulation
and artificial blockage of cortisol synthesis with metronome have been performed.Slide15
While the assessment of cortisol in sweat or tears is only of theoretical importance and urinary cortisol of decreasing interest, salivary cortisol
has become an invaluable tool for both basic scientists and clinicians. A number of significant advantages over the assessment of
cortisol
in blood has resulted in an steadily increasing interest in salivary
cortisol
.Slide16
Q: Does the concentration of cortisol in saliva accurately reflect the level in blood? A:Yes, when compared to the amount of unbound cortisol in serum or plasma samples. A number of studies have revealed correlations between the two specimen of r > 0.90. However, the correlation between the total cortisol levels in blood and salivary cortisol is usually weaker due to different amounts of CBG found in blood (e.g., high levels of CBG due to oral contraceptive use results in high total cortisol levels; free cortisol levels are usually unaltered in states of increased CBG). Slide17
Q: Does the salivary cortisol levels depend on saliva flow rate?A:No. Studies looking at salivary cortisol levels obtained under minimal and maximal flow rate clearly showed that the cortisol
levels in saliva do not depend on flow rateSlide18
Preparation of client:The specimen is usually drawn in the morning after the client has been fasting. Evening samples may also require about 3 hour of fasting. Water is allowed. Because activity increases the level, the client needs to be supine for 2 hour before the test
.
Cortisol is excreted primarily in urine in an unbound free form
Salivary cortisol:
For research studies, salivary cortisol is simple noninvasive way to obtain a physiological index of stress.Slide19
You may be asked to avoid strenuous physical activity the day before the test.Be sure to drink enough fluids during the 24-hour urine test. This prevents dehydration .Many
medicines
may change the results of this test. Be sure to tell your doctor about all the
non-prescription
and
prescription medicines you take.
Talk to your doctor about any concerns you have regarding the need for the test, its risks, how it will be done, or what the results will meanSlide20
Increased serum cortisol level significance: an increase in cortisol can either ACTH-dependent or ACTH- independent.The specific medical treatment of elevated cortisol levels depends on the cause.The client may undergo a battern of tests to determine whether there is
a tumor of the pituitary
gland
or of the adrenal gland
.
Decrease serum cortisol
level clinical significance: the lack of cortisol in the serum may be due to primary
hypofunction of the adrenal cortex
, or it may be secondary to
hypo functioning of the pituitary gland
. Slide21
Once the symptoms of a lack of cortisol and aldosterone are recognized and confirmed, replacement therapy is started. Until the hormones are replaced, or when the need is greater than the supply, these clients may have problems related to the lack of cortisol and aldosterone.Slide22
Cortisone is a synthetic version of cortisolCortisol and cortisone are both
steroids
. They share a similar core chemical structure which is common to all the cholesterol-like molecules. They comprise 4 fused carbon rings and, therefore, have a very rigid structure. The difference between
cortisol
and cortisone lies in
the difference of the functional groups present in the two molecules
.
When the adrenal glands do not make enough
cortisol
, this is called
adrenal insufficiency,
the treatment is
hydrcortisonSlide23
V.M.A
Generally, unfortunately most of the hormones are present in blood in such
small amounts
that their measurement is
very difficult
.
Some of hormones or their
metabolites
are excreted in the urine and in many instances their concentration in urine is much greater than in blood. Since it is much easier to obtain a few hundred milliliters of urine, than, say,20 ml of blood, some hormone analysis may be done with urine. Since the hormone excretion rate may vary during the day. The use of a
24 hour urine specimen
gives more accurate results. Slide24
Not all hormones are excreted in the urine in appreciable amounts, those of lower molecular weight, e.g. the steroids, are more likely to be found in the urine in measurable amounts than are larger molecules such as the pituitary hormones. In some instances the hormone itself may not be excreted in the urine in large quantities, but various
metabolites of the hormone
may be found. The measurement of these metabolites sometimes gives satisfactory
estimate
of the amount of original hormone present in the blood. Slide25
Vanillylmandelic Acid, 24 hr urine. Vanillylmandelic acid (VMA) is one of the metabolites of the catecholamines
epinephrine
(adrenaline) and norepinephrine
. This test measures the amount of VMA that is excreted into the urine, typically over a 24-hour period,
to detect excess catecholamine production.Slide26
Useful ForScreening children for catecholamine-secreting tumors. Supporting a diagnosis of neuroblastoma
Monitoring patients with a treated
neuroblastoma
The measurement of urinary
metanephrines
plus VMA have been suggested as the best screening procedure for the detection of
pheochromocytomas
.Slide27
VMA is usually present in the urine in small fluctuating amounts that only increase appreciably during and shortly after the body is exposed to a stressor. (24 hr is the best)Neuroblastomas, pheochromocytomas, and other neuroendocrine
tumors
, however, can produce large amounts of
catecholamines
, resulting in greatly increased concentrations of the hormones and their metabolites.
The hormone releases can cause persistent hypertension, severe headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.Slide28
patient Preparation Abstain from medications for 72 hours prior to collection. Collect 24-hour or random urine. Refrigerate 24-hour specimens during collection. Storage/Transport Temperature Refrigerated.
Unacceptable
Conditions:
Specimen types other than urine.
Stability Ambient: Unacceptable; Refrigerated: 1 week; Frozen: 2 weeks Slide29
dehydroepiandrosterone(DHEA)HomeworkSlide30