Download MBBS Adrenal Function Tests Lecture PPT

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