Download MBBS Adrenal Function Tests Lecture PPT

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TESTS

DR. S. SHEKHAR

ASSOC. PROFESSOR

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DEPT. OF BIOCHEMISTRY
Adrenal Glands

SUPRARENAL GLANDS or ADRENAL GLANDS

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? Paired organ each weight

about 4 grams, pyramidal in
shape, located on the top of

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the kidneys, one on each side
at the level of T12

? It is enclosed by fibro elastic

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connective tissue - capsule
Adrenal Glands

Each gland is divided into two parts:
? Cortex

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? outer part of gland
? Part of hypothalamus ? pituitary ? adrenal axis
? Secrete a variety of steroid hormones
? Medulla
? inner part of gland, (20% of gland)

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? Part of sympathetic nervous system
? Secrete catecholamines
? Both parts are structurally and functionally different
Histology of adrenal glands
Adrenal cortex

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? Zona glomerulosa:
? Produce mineralocorticods
? Mainly aldosterone (because it contain

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enzyme aldosterone synthase)

Hormones that help control the balance of minerals
(Na+ and K+) and water in the blood
Adrenal cortex

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ALDOSTERONE SECRETION
Adrenal cortex

Zona fasciculata

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? Produce glucocorticods
? Mainly cortisol and corticosterone
? The human adrenal glands produce the equivalent of

35?40 mg of cortisone acetate per day

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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

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hypothalamic-pituitary axis via ACTH
Adrenal cortex

Zona reticularis

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? The innermost layer of the adrenal cortex, lying

deep to the zona fasciculata and superficial to the
medulla

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? These cells produce androgens
Adrenal cortex

Zona reticularis

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?The androgens produced includes
. Dehydroepiandrosterone (DHEA)

.

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. Androstenedione

? Synthesized from cholesterol
? DHEA is further converted to DHEA-sulfate via a

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sulfotransferase

? The androgens produced are released into the blood

stream and taken up in the testis and ovaries to

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produce testosterone and the estrogens respectively
Regulation of
adrenal gland
secretion

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ADDISON'S DISEASE
CUSHING DISEASE SYMPTOMS
ADRENAL

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FUNCTION TESTS

TESTS FOR

TESTS FOR

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GLUCOCORTICOID

MINERALOCORTICOID

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ACTIVITY

ACTIVITY

SCREENING

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CONFIRMATORY

PLASMA

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TESTS

TEST

ALDOSTERONE

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SCREENING

TESTS FOR

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GCC

PRELIMINARY

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ESTIMATION OF

ASSESMENT OF

SCREENING

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URINARY FREE

DIURNAL RHYTHM

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TEST

CORTISOL

OF PLASMA

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CORTISOL
ACTH STIMULATION TEST

METYRAPONE

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STIMULATION TEST

CONFIRMATORY

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CRH STIMULATION

TEST FOR GCC

TEST

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MEASUREMENT OF PLASMA ACTH

DEXAMETHASONE SUPPRESSION TEST
A. TESTS FOR GLUCOCORTICOID FUNCTIONS

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SCREENING TESTS

1. PRELIMINARY SCREENING TEST
- The most potent effect of GCC is on carbohydrate

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metabolism.

- so evaluation of blood sugar and plasma cortisol at

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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

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cotex lesion.

- The initial screening is followed by further definite

test

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2. ASSESMENT OF DIURNAL RHYTHM OF

PLASMA CORTISOL

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? Plasma cortisol levels are about 10 times higher in the

early morning hours than at midnight.

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? 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

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of a lesion at any point in the hypothalamic ?pituitary

?adrenal axis.

? Stress such as trauma, pain, apprehension, fever and

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hypoglycemia can also override this diurnal rhythm
3.

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Estimation of Urinary Free Cortisol

? Another useful screening test
? Urinary cortisol secretion is higher during day time (7

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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

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renal function and adequqte urine collection.

? Urine cortisol ranges from 10-100 ?g/day.
? Levels of urine cortisol increases in hyperadrenalism

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and decrease in hypoadrenalism.
CONFIRMATORY TEST FOR ADRENAL

CORTEX FUNCTION

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? If the preliminary test shows that the adrenal function

is increased (hyperadrenalism) or decreased
(hypoadrenalism) then they are confirmed by further

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tests

? Hyperadrenalism is confirmed by SUPPRESSION

TEST

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? Hypoadrenalism is confirmed by STIMULATION

TEST.

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? These tests evaluate the pituitary adrenal axis and also

the adrenal reserve.
1.DEXAMETHASONE SUPPRESSION TEST

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A. LOW DOSE DEXAMETHASONE

SUPPRESSION TEST

? This test is recommended if results of urinary

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free cortisol test are abnormal.

? Dexamethasone is a potent suppressor of

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pituitary ACTH and cortisol level.

? It causes about 50% fall in serum cortisol with a

dose as low as 2mg .

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The

patient

takes

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2mg

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of

dexamethasone at night

The next morning 8:00 AM plasma

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cortisol level is determined.

A morning cortisol level less than

5?g/dL is considered normal

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Higher level is indicative of

hyperfunction of adrenal cortex.
B. HIGH DOSE DEXAMETHASONE

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SUPPRESSION TEST

This test is carried out with administration of 2 mg

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dexamethasone every 6 hours for 2 days while
collecting urine for 24 hrs.

Plasma and urine cortisol is determined

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If these parameters are not

There is suppression of

suppressed , adrenal tumors

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plasma cortisol in pituitary

producing high levels of

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dependent Cushing disease

cortisol or ectopic ACTH

.

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producing tumors are usually
the aetiology

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2. Measurement of plasma ACTH

? Cortisol and ACTH interact in a feedback loop.
? Low levels of plasma cortisol associated with high

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plasma ACTH would indicate primary adrenocortical
insufficiency.

? Likewise increased plasma cortisol will be associated

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with suppression of ACTH in primary adrenal lesion.

? In contrast, increased cortisol due to an ACTH

producing pituitary adenoma ( Cushing's disease) or

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due to ectopic production of ACTH will be associated
with increased plasma ACTH levels.
3. ACTH STIMULATION TEST

? Useful in assessing adrenal reserve capacity

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? Also used for documenting the existence of

hormonal deficiency state.

? The test uses a synthetic form of ACTH

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(Synacthen)

? It consists of first 24 amino acids of ACTH,

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which is injected IM/ IV
A. SHORT ACTH STIMULATION TEST

? 250 ?g Synacthen is administered intramuscularly or

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intravenously

? Basal and post ACTH administration, cortisol

measurement at 30 and 60 minutes is done.

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? 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.

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? Lower results show hypofunction of adrenal.
? Whereas a person with primary adrenal failure does

not respond.

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B. LONG ACTH STIMULATION TEST

? Here, lower dose of 1?g/day of ACTH is

administered for several days to effectively

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stimulate adrenals than single dose of 250?g.

? This successfully assesses the adrenal

insufficiency.

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4. METYRAPONE STIMULATION TEST

? This test is used to

delineate

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cause

of

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Cushing's syndrome.

? Metyrapone is a potent

inhibitor of the

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11-hydroxylase enzyme
so blocks cortisol
synthesis.

11-hydroxylase

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METYRAPONE
? Measures the ability of

the pituitary gland to release

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ACTH in response to decreased blood cortisol levels

? Hypothalmic pituitary axis responds by releasing

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more ACTH and so increases the concentration of 11-
deoxycortisol due to inhibition of 11-hydroxylase

? Likewise

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the

urinary

excretion

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of

17-

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hydroxycorticosteroid also increases.

? In Cushing's syndrome caused by a pituitary tumor,

the ACTH response remains intact and 11

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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.

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5. CRH STIMULATION TEST

? To differentiate between secondary adrenal

insufficiency due to pituitary or hypothalamic

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disease.

? Results :
Pituitary disease ? blunted or nil response
Hypothalamic lesions ? positive response

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B. TESTS FOR

MINERALOCORTICOID ACTIVITY

A. PLASMA ALDOSTERONE

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? Levels of plasma aldosterone are more in

morning than in evening.

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? Morning blood levels in supine position are 6

-22 ?g/dL in males and 5-30 ?g/dL in
females.

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? Levels increase in hyperaldosteronism and

low in hypoaldosteronism.
A. STIMULATION TEST

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? The stimulation test use volume depletion by
- salt restriction

These act as stimulant

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- use of diuretic

which increases renin

- up right posture

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activity leading to high
aldosterone secretion

? Salt restricted diet 0.5-0.6g of dietary salt / day for 3-

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4 days leads to 2-3 times increase over the basal
levels of aldosterone.
B. SUPPRESSION TEST

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? High sodium leads to volume expansion

leading to decrease in plasma renin level which
in turn decreases aldosterone.

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? Normal saline infusion 500 ml/hour for 4 hours

should lead to a plasma aldosterone level of
less than 8 ?g/dL.
ADRENAL MEDULLA

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Synthesis of

catecholamines.

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DOPA = Dihydroxyphenylalanine,

PNMT=Phenylethanolamine-

Nmethyl transferase.

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ADRENAL MEDULLA

Metabolism of

catecholamines

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COMT = Catechol-O-

methyltransferase,

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MAO = Monoamine

oxidase
PHAEOCHROMOCYTOMA

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? Tumour of the adrenal medulla, which is derived from

chromaffin cells catecholamines

? Occur around 4th decade, earlier in hereditary type

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? Known as "10% tumor

Symptoms
Lab. investigation

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? Urine
-Determination of adrenaline, noradrenaline,

metanephrine, normetanephrine levels in a
24hour urine collection

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? Plasma
-free metanephrine& normetanephrine