Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Adrenal Function Tests Lecture PPT
ADRENAL
FUNCTION
TESTS
DR. S. SHEKHAR
ASSOC. PROFESSOR
DEPT. OF BIOCHEMISTRY
Adrenal Glands
SUPRARENAL GLANDS or ADRENAL GLANDS
? Paired organ each weight
about 4 grams, pyramidal in
shape, located on the top of
the kidneys, one on each side
at the level of T12
? It is enclosed by fibro elastic
connective tissue - capsule
Adrenal Glands
Each gland is divided into two parts:
? Cortex
? outer part of gland
? Part of hypothalamus ? pituitary ? adrenal axis
? Secrete a variety of steroid hormones
? Medulla
? inner part of gland, (20% of gland)
? Part of sympathetic nervous system
? Secrete catecholamines
? Both parts are structurally and functionally different
Histology of adrenal glands
Adrenal cortex
? Zona glomerulosa:
? Produce mineralocorticods
? Mainly aldosterone (because it contain
enzyme aldosterone synthase)
Hormones that help control the balance of minerals
(Na+ and K+) and water in the blood
Adrenal cortex
ALDOSTERONE SECRETION
Adrenal cortex
Zona fasciculata
? Produce glucocorticods
? Mainly cortisol and corticosterone
? The human adrenal glands produce the equivalent of
35?40 mg of cortisone acetate per day
Hormone that play a major role in glucose metabolism
as well as in protein and lipid metabolism
? The secretion of these cells is controlled by
hypothalamic-pituitary axis via ACTH
Adrenal cortex
Zona reticularis
? The innermost layer of the adrenal cortex, lying
deep to the zona fasciculata and superficial to the
medulla
? These cells produce androgens
Adrenal cortex
Zona reticularis
?The androgens produced includes
. Dehydroepiandrosterone (DHEA)
.
. Androstenedione
? Synthesized from cholesterol
? DHEA is further converted to DHEA-sulfate via a
sulfotransferase
? The androgens produced are released into the blood
stream and taken up in the testis and ovaries to
produce testosterone and the estrogens respectively
Regulation of
adrenal gland
secretion
ADDISON'S DISEASE
CUSHING DISEASE SYMPTOMS
ADRENAL
FUNCTION TESTS
TESTS FOR
TESTS FOR
GLUCOCORTICOID
MINERALOCORTICOID
ACTIVITY
ACTIVITY
SCREENING
CONFIRMATORY
PLASMA
TESTS
TEST
ALDOSTERONE
SCREENING
TESTS FOR
GCC
PRELIMINARY
ESTIMATION OF
ASSESMENT OF
SCREENING
URINARY FREE
DIURNAL RHYTHM
TEST
CORTISOL
OF PLASMA
CORTISOL
ACTH STIMULATION TEST
METYRAPONE
STIMULATION TEST
CONFIRMATORY
CRH STIMULATION
TEST FOR GCC
TEST
MEASUREMENT OF PLASMA ACTH
DEXAMETHASONE SUPPRESSION TEST
A. TESTS FOR GLUCOCORTICOID FUNCTIONS
SCREENING TESTS
1. PRELIMINARY SCREENING TEST
- The most potent effect of GCC is on carbohydrate
metabolism.
- so evaluation of blood sugar and plasma cortisol at
8:00 AM are the initial tests.
- A high blood sugar or low sugar level along with
changes in cortisol levels go in favour of adrenal
cotex lesion.
- The initial screening is followed by further definite
test
2. ASSESMENT OF DIURNAL RHYTHM OF
PLASMA CORTISOL
? Plasma cortisol levels are about 10 times higher in the
early morning hours than at midnight.
? Normal range for plasma cortisol
At 8:00 AM ? 8-26?g/dL
At 12:00 AM - < 1?g/dL
? Loss of this diurnal rhythmicity is an early indication
of a lesion at any point in the hypothalamic ?pituitary
?adrenal axis.
? Stress such as trauma, pain, apprehension, fever and
hypoglycemia can also override this diurnal rhythm
3.
Estimation of Urinary Free Cortisol
? Another useful screening test
? Urinary cortisol secretion is higher during day time (7
AM ? 7 PM) than night (7 PM ? 7 AM). Hence a
properly collected 24 hours urine sample is required.
? Urine creatinine should also be measured to assess
renal function and adequqte urine collection.
? Urine cortisol ranges from 10-100 ?g/day.
? Levels of urine cortisol increases in hyperadrenalism
and decrease in hypoadrenalism.
CONFIRMATORY TEST FOR ADRENAL
CORTEX FUNCTION
? If the preliminary test shows that the adrenal function
is increased (hyperadrenalism) or decreased
(hypoadrenalism) then they are confirmed by further
tests
? Hyperadrenalism is confirmed by SUPPRESSION
TEST
? Hypoadrenalism is confirmed by STIMULATION
TEST.
? These tests evaluate the pituitary adrenal axis and also
the adrenal reserve.
1.DEXAMETHASONE SUPPRESSION TEST
A. LOW DOSE DEXAMETHASONE
SUPPRESSION TEST
? This test is recommended if results of urinary
free cortisol test are abnormal.
? Dexamethasone is a potent suppressor of
pituitary ACTH and cortisol level.
? It causes about 50% fall in serum cortisol with a
dose as low as 2mg .
The
patient
takes
2mg
of
dexamethasone at night
The next morning 8:00 AM plasma
cortisol level is determined.
A morning cortisol level less than
5?g/dL is considered normal
Higher level is indicative of
hyperfunction of adrenal cortex.
B. HIGH DOSE DEXAMETHASONE
SUPPRESSION TEST
This test is carried out with administration of 2 mg
dexamethasone every 6 hours for 2 days while
collecting urine for 24 hrs.
Plasma and urine cortisol is determined
If these parameters are not
There is suppression of
suppressed , adrenal tumors
plasma cortisol in pituitary
producing high levels of
dependent Cushing disease
cortisol or ectopic ACTH
.
producing tumors are usually
the aetiology
2. Measurement of plasma ACTH
? Cortisol and ACTH interact in a feedback loop.
? Low levels of plasma cortisol associated with high
plasma ACTH would indicate primary adrenocortical
insufficiency.
? Likewise increased plasma cortisol will be associated
with suppression of ACTH in primary adrenal lesion.
? In contrast, increased cortisol due to an ACTH
producing pituitary adenoma ( Cushing's disease) or
due to ectopic production of ACTH will be associated
with increased plasma ACTH levels.
3. ACTH STIMULATION TEST
? Useful in assessing adrenal reserve capacity
? Also used for documenting the existence of
hormonal deficiency state.
? The test uses a synthetic form of ACTH
(Synacthen)
? It consists of first 24 amino acids of ACTH,
which is injected IM/ IV
A. SHORT ACTH STIMULATION TEST
? 250 ?g Synacthen is administered intramuscularly or
intravenously
? Basal and post ACTH administration, cortisol
measurement at 30 and 60 minutes is done.
? There should be a minimum rise of more than 7?g/dL
over the basal level or plasma level should be more
than 18?g/dL.
? Lower results show hypofunction of adrenal.
? Whereas a person with primary adrenal failure does
not respond.
B. LONG ACTH STIMULATION TEST
? Here, lower dose of 1?g/day of ACTH is
administered for several days to effectively
stimulate adrenals than single dose of 250?g.
? This successfully assesses the adrenal
insufficiency.
4. METYRAPONE STIMULATION TEST
? This test is used to
delineate
cause
of
Cushing's syndrome.
? Metyrapone is a potent
inhibitor of the
11-hydroxylase enzyme
so blocks cortisol
synthesis.
11-hydroxylase
METYRAPONE
? Measures the ability of
the pituitary gland to release
ACTH in response to decreased blood cortisol levels
? Hypothalmic pituitary axis responds by releasing
more ACTH and so increases the concentration of 11-
deoxycortisol due to inhibition of 11-hydroxylase
? Likewise
the
urinary
excretion
of
17-
hydroxycorticosteroid also increases.
? In Cushing's syndrome caused by a pituitary tumor,
the ACTH response remains intact and 11
deoxycortisol level show marked rise (>200 nmol/L)
? Levels of 11 deoxycortisol that are less than this are
consistent with adrenal tumour or ectopic ACTH.
5. CRH STIMULATION TEST
? To differentiate between secondary adrenal
insufficiency due to pituitary or hypothalamic
disease.
? Results :
Pituitary disease ? blunted or nil response
Hypothalamic lesions ? positive response
B. TESTS FOR
MINERALOCORTICOID ACTIVITY
A. PLASMA ALDOSTERONE
? Levels of plasma aldosterone are more in
morning than in evening.
? Morning blood levels in supine position are 6
-22 ?g/dL in males and 5-30 ?g/dL in
females.
? Levels increase in hyperaldosteronism and
low in hypoaldosteronism.
A. STIMULATION TEST
? The stimulation test use volume depletion by
- salt restriction
These act as stimulant
- use of diuretic
which increases renin
- up right posture
activity leading to high
aldosterone secretion
? Salt restricted diet 0.5-0.6g of dietary salt / day for 3-
4 days leads to 2-3 times increase over the basal
levels of aldosterone.
B. SUPPRESSION TEST
? High sodium leads to volume expansion
leading to decrease in plasma renin level which
in turn decreases aldosterone.
? Normal saline infusion 500 ml/hour for 4 hours
should lead to a plasma aldosterone level of
less than 8 ?g/dL.
ADRENAL MEDULLA
Synthesis of
catecholamines.
DOPA = Dihydroxyphenylalanine,
PNMT=Phenylethanolamine-
Nmethyl transferase.
ADRENAL MEDULLA
Metabolism of
catecholamines
COMT = Catechol-O-
methyltransferase,
MAO = Monoamine
oxidase
PHAEOCHROMOCYTOMA
? Tumour of the adrenal medulla, which is derived from
chromaffin cells catecholamines
? Occur around 4th decade, earlier in hereditary type
? Known as "10% tumor
Symptoms
Lab. investigation
? Urine
-Determination of adrenaline, noradrenaline,
metanephrine, normetanephrine levels in a
24hour urine collection
? Plasma
-free metanephrine& normetanephrine
This post was last modified on 30 November 2021