• Corticosteroid hormones(cortisol an
dihydroxycortisol) - to help control the body's use
of fats, proteins, and carbohydrates.
• Aldosterone - inhibits the level of sodium
excreted into the urine, and maintains blood
volume and blood pressure.
• Androgenic steroids (androgen hormones) -
hormones that have an effect on the development
of male characteristics.
• Epinephrine (adrenaline) - increases the heart
rate and force of heart contractions.
• Norepinephrine (noradrenaline) - this
hormone has little effect on smooth
muscle, metabolic processes, and cardiac
output, but has strong vasoconstrictive effects
• produced by the zona fasciculata of the adrenal cortex.
• Its primary functions are to increase blood sugar through
• A cortisol level lower than 6 micrograms per deciliter of
blood may indicate Addison's disease or hypopituitarism.
• Cortisol levels above 23 micrograms per deciliter can be a
sign of adrenal tumor or Cushing's syndrome.
Synthesized and released into bloodstream by zona
glomerulosa of the adrenal gland
Average daily production is 0.1 to 0.7 μml (50 to 250 μg) with
normal salt intake.
Inactivated in liver by conjugation with glucuronic acid or sulfuric
Secretion is regulated by renin-angiotensin system (main
regulator), serum potassium concentration and ACTH levels
.Decrease in effective circulating blood volume increases
aldosterone via renin-angiotensin axis
Increase in serum potassium increases aldosterone levels
ACTH plays a minor role in regulation of aldosterone synthesis
Aldosterone secretion in healthy subjects is increased by low-
salt diet (< 2 gm/day), stress, upright posture and diuretic
therapy, and is decreased by high salt diet or lying supine (lying
down with face up)
Major regulator of effective circulating blood volume
● Increases renal reabsorption of sodium and water to maintain blood
pressure and tonicity
● Acts through mineralocorticoid receptors in renal cortical collecting
● Also increases urinary excretion of potassium and hydrogen ions
● Recently discovered to have an effect on endothelium and coronary
Plasma aldosterone - supine position and normal sodium
diet: 209 ng/dl (55-250 pmol/L)
● Plasma aldosterone - upright position (standing/seated
for at least 2 hr) and normal sodium diet: 2-5x supine
● Urine aldosterone: 5-20 μmg/24 hr (14-56 nmol/24 hr)
● Conversion factor: multiply by 0.0277 to convert from
ng/dl to nmol/L
High values: primary
hyperaldosteronism, aldosterone secreting
adrenal tumor, idiopathic adrenal
Low values: adrenal insufficiency, congenital
adrenal hyperplasia due to 11-beta-hydroxylase
Includes androstenedione and DHEAS
Normal plasma levels of:
a)DHEAS is 4.5-18.8 mumol/l In men and 3.5 -
17.8 mumol/l in women
b)Androstenedione is 2.1 -7.7 in men and 3.3 -
9.9 in women
Elevated levels of this hormones lead to
• Include norepinephrine (decapeptide) and
• About half of plasma dopamines produced in
the adrenal medulla
• The plasma free dopamine level is about 35
pg/mL (0.23 nmol/L)
• Increased level is due to factors such as
hypoglycemia ,surgery,ketoacidosis ,exercise
and myocardial infarction
• Relative adrenal insufficiency is present when adrenal response is
inadequate for the stress situation-highest levels of baseline
-but do not respond to the ACTH
absolute adrenal insufficiency is characterized by low levels of
baseline cortisol and by non-response to the ACTH stimulation test.
Functional tests and their medical
1.Random cortisol level Test
• Cortisol’s normal diurnal variation is often lost in critically ill
patients, so cortisol can be measured at any time during stress.
• 2.The ACTH stimulation test
• It is performed to evaluate adrenal gland response and
reserve, i.e., it is important to detect relative adrenal insufficiency.
During the standard ACTH stimulation test, cortisol is measured
before and then 30 and 60 minutes after cosyntropin (Cortrosyn;
ACTH 1-24) 250 mg is given intravenously or intramuscularly. The
test can be performed at any time of day with similar maximum
• may not detect partial adrenal insufficiency in patients with
hypothalamic or pituitary disorders,
• 3. Low-dose test
• The dose of cosyntropin used in the standard ACTH
stimulation test—250 μg—is a large overdose. For this
reason and to improve the test’s sensitivity in detecting
partial secondary or tertiary adrenal insufficiency, the low-
dose ACTH stimulation test has been adopted, which uses
cosyntropin 1 mg intravenously. The low-dose test is more
sensitive in detecting partial adrenal insufficiency in
critically ill patients.
• The cortisol level at 30 minutes during the standard ACTH
stimulation test is similar to the result during the low dose
test. For this reason, the standard test is normally
used, with a cortisol threshold of 20 mg/dL at 30 minutes.
4. Delta 9” as a cutoff value
• The “delta” value during the ACTH stimulation
test is the difference between the baseline and
the maximum cortisol value at either 30 or 60
• Delta 9 (9 mg/mL) is the cutoff for diagnosing
relative or functional adrenal insufficiency in
patients with septic shock in an intensive care
• The delta value is a measure of adrenal reserve
5. Free cortisol test
• About 70% of circulating cortisol is tightly bound to
cortisol-binding globulin (CBG), and about 10% to 20% is
loosely bound to albumin.
• That only free cortisol is biologically active. Free cortisol
levels in thus dependeds on the serum albumin level.
• Patients with hypoalbuminemia (albumin levels ≤2.5 g/dL)
have significantly lower basal and stimulated total cortisol
levels during the ACTH stimulation test, and nearly 40% of
them have a stimulated total cortisol level ≤18.5 μg/dL.
• In critically ill patients with hypoalbuminemia , total serum
cortisol may be a poor indicator of glucocorticoid activity
• The metyrapone test was developed to evaluate pituitary reserve
• Metyrapone inhibits enzyme P450C11, which converts 11-
deoxycortisol (compound S) into cortisol, consequently reducing
serum levels of cortisol and increasing 11-deoxycortisol levels.
• Reduction in serum cortisol stimulates release of ACTH by
feedback, acting at a hypothalamic-pituitary level.
• Adequate adrenal production occurs when compound S is higher
than 7.0 μg/dL, independent of cortisol value.
• Required waiting time for its execution is at least 8 hours between
administration of metyrapone and serum dosages.