• The body has two adrenal ( supra renal)
glands, each located on the superior pole of
each kidney. Each adrenal gland is structurally
and functionally differentiated into two
regions or zones:
1. Adrenal cortex:
This is the outer or peripheral zone of the
adrenal gland, which makes up the bulk of
2. Adrenal medulla:
This is the inner zone of the adrenal gland.
• The adrenal cortex is divided into three zones.
Each zone has a different cellular arrangement
and secretes different groups of steroid
• The layers/zones of the adrenal cortex.
Formula for remembering layers. (GFR)
This is the outer most zone of the adrenal
cortex which secretes mineralocorticoids.
This is the middle zone of the adrenal cortex
which secretes glucocorticoids and adrenal
This is the inner most zone of the adrenal cortex
which secretes glucocorticoids and adrenal
androgen, but in a small quantities.
HORMONES OF THE ADRENAL CORTEX
• The adrenocortical hormones and their
functions in the body are classified into:
3. Adrenal androgens
• These hormones help to control the water and
electrolyte homeostasis, particularly the
concentration of Na+ and K+ ions.
Mineralocorticoids include the following
a) Aldosterone ( principal hormone).
b) Deoxy corticsterone.
• The glucocorticoids are group of hormones
concerned with normal organic metabolism
and resistance to stress. Glucocorticoids
include the following hormones:
e) Mythyl prednisone.
3. ADRENAL ANDROGENS
• These are steroids which exhibit actions similar to
Biosynthesis of adrenocortical hormones:
Progesterone Cortisol Androgen
This is a hormone of the adrenal cortex,
secreted by the outermost layer called the zone
Daily secretion = 150 ug/day.
Normal plasma level : 6 ng/100 ml.
• The secretion of aldosterone is caused by?
• a) angiotensin II
• b) ACTH
• c) epinephrine
• d) insulin
• Aldosterone secretion is regulated by the
• a) ACTH
• b) calcium
• c) blood volume
• d) potassium
The half-life of aldosterone is short, about 20
Most of the secreted aldosterone is bound to
albumin, with a lesser amount bound to
corticosteroid binding globulin (CBG). The
transport is as follows:
I. 60% bound with plasmaproteins (mostly
II. 40% transported in free form.
Most aldosterone is converted in the liver to a
tetra hydroglucronide derivative, but some is
changed in the liver and kidneys to an 18
glucronide. The glucronide which is unlike the
breakdown products of other steroids. It is
converted to free aldosterone by hydrolysis at a
pH of 1.0 and is therefore referred to as the “
Less than 1% of the secreted aldosterone
appears in the urine in free form. 5% is in
the form of “acid labile conjugate” and
upto 40% is in the form of the
• REGULATION OF ALDOSTERONE SECRETION:
A. Factors increasing aldosterone secretion:
a) Increased K+ ions.
b) Decreased Na+ ions.
c) Undefined pituitary factors.
g) Increased renin angiotensin.
i) Adrenal adenoma (Conn’s Syndrome)
j) Idiopathic adrenal hyperplasia.
Factors stimulating aldosterone release from
the adrenal cortex:
Angiotensin II is the most
important trophic factor for the zona glomerulosa
and one of the two most important stimulators of
aldosterone release. Even a 0.5 mM increase in
plasma [K] stimulates aldosterone release. In turn,
aldosterone regulates plasma [K] by promoting K
secretion in the collecting ducts. Angiotensin III
has 100% aldosterone releasing activity but only
40% of the pressor activity of aldosterone. ACTH
as well as a decrease in plasma [Na] stimulate
aldosterone release but the stimulatory effects of
acute administration of pharmacologic doses of
ACTH on aldosterone release are transient if at all.
• When excess aldosterone is administered, it
causes excess Na+ and water absorption
increasing ECF volume, in turn increasing
blood volume. Increased blood volume causes
increased cardiac output and blood pressure.
Pressure diuresis and pressure natriuresis
cause a secondary loss of Na+ and water. This
process is called aldosterone escape.
EFFECTS OF ALDOSTERONE
• A. Effects on renal tubules:
The main action of aldosterone is to maintain
balance of the electrolyte contents of the body
fluid. The sites of action are the ascending limb,
loop of Henle, and distal and collecting tubules.
i) Aldosterone causes increased tubular
reabsorption of Na+ in exchange for K+ and H+
ions. The lack of aldosterone causes an excess
loss of Na+ in urine.
ii) Aldosterone increases K+ secretion into
the distal and collecting tubules of the
kidneys. This may be due to ionic exchange
with Na+ reabsorption. Excess aldosterone
causes hypokalemia and muscle paralysis.
iii) Aldosterone causes water absorption
due to the concentration gradient created
by Na+ absorption, increasing EFC volume.
B. General effects on:
i. Circulation: increases blood volume and
ii. Blood pressure: increases blood
pressure due to increased cardiac
output, blood volume and venous
iii. Sweat glands and salivary glands:
aldosterone causes increases Na+ and Cl-
reabsorption. And at the same time, it
increases K+ secretion.
iv. GIT: causes increased Na+ and Cl-
absorption from the intestine,
simultaneously increasing water
reabsorption from GIT.
Cortisol is also known as hydrocortisone. This
hormone is most abundunt and essential for life.
It is responsible for about 90% of glucocorticoid
• Site of formation:
Cortisol is secreted by the zona fasiculata and
zona reticularis layers of the adrenal cortex of
the adrenal gland
This hormone is a 21 carbon atom steroid which
is synthesized from acetyl-CoA cholesterol.
Daily secretion rate = 15 mg/day
Half-life = 90 – 100 minutes
Normal plasma level = 94% bound with cortisol
binding protein, 6% in
• Regulation of cortisol:
The secretion of glucocorticoids is
regulated by hormone of anterior pituitary
gland called adrenocortcotropic hormone
The control of glucocorticoid secretion is
under a typical negative feedback
mechanism. The two principle stimuli are
stress and low blood level of
• Regulation of cortisol:
Both conditions stimulate the
hypothalamus to secrete a regulating
hormone called corticotropin releasing
hormone(CRH). This secretion initiates the
release of ACTH from the anterior pituitary
gland. ACTH is carried through blood to the
adrenal cortex where it stimulates glucocorticoid
• Effects of cortisol:
A. Metabolic effects:
1. Carbohydrate metabolism:
a) Cortisol stimulates gluconeogenesis in
the liver by mobilizing amino acids from
extra hepatic tissues (muscles) and by
increasing the enzymes of
b) It decreases the utilization of glucose by
cells by decreasing oxidation of NADH2,
which is needed for glycolysis, and by
decreasing glucose transport into the cells.
c) It increases blood glucose levels due to
increased gluconeogenesis and decreases
glucose utilization. This condition is called
2. Protein metabolism:
a) The principle effects of cortisol on the
metabolic systems of the body is reduction of
protein stores in all body cells except those of
the liver. This is caused by both decreased
protein synthesis and increases catabolism of
protein in the cells.
b) It inhibits amino acid entry into all cells
except the liver.
c) It increases amino acid concentration in
d) It increases urea level in blood.
3. Fat metabolism:
a) It mobilizes fatty acids from adipose tissues.
b) It increases free fatty acid concentrations in
c) It increases utilization of free fatty acids for
d) It causes ketosis due to increased conversion
of free fatty acids into acetyls-CoA.
4. Electrolyte metabolism:
a) It promotes Na+ and Cl- retention from the
b) It increases excretion of K+ by kidneys.
5. Water metabolism:
It causes diuresis by suppressing ADH secretion
or by increasing destruction of ADH by the liver
B. General effects:
a) Cortisol increases blood pressure
because of increased production of
b) Increased sensibility of vascular smooth
muscle to nor-adrenaline and
2. On blood cells:
a) Increases the platelet count.
b) Decreases blood clotting time.
c) Increases total WBCs.
d) Decreases lymphocytes, eosinophils and
e) Increases neutrophils, monocytes and RBC
3. On C.N.S. :
a) Low cortisol levels cause restlessness,
insomnia, and inability to concentrate.
b) Causes excitation of the CNS.
4. On GIT:
a) Increases gastric acidity and may cause a
5. On bone:
a) Excess cortisol may cause a defect in the
synthesis of protein matrix.
b) It decreases the deposition of calcium.
c) It increases the loss of calcium in urine.
d) It decreases absorption of calcium from
6. On infection, inflammation, and trauma:
a) Large doses of cortisol decrease the
formation of antibodies due to its destructive
effect on lymphoid tissues.
b) It decreases tissue response to bacteria.
c) It is anti- inflammatory.
d) It is anti- allergic.
e) It delays wound healing.
PATHOLOGY OF ADRENAL CORTEX
• ADDISON’S DISEASE:
This disease results from failure of adrenal cortex to
produce adrenocortical hormones.
1. Atrophy of the adrenal cortex.
3. Surgical removal of adrenal gland.
5. Deficiency of enzymes (responsible for the formation
6. Hemorrhage and infarction.
7. Meningococal septicaemia.
9. Schilder’s disease.
Clinical features of Addison's disease:
Weight loss, anorexia, malaise, fever,
depression, impotence, abdominal pain, nausea,
vomiting, diarrhoea, syncope, constipation etc.
General wasting, loss of weight, loss of body
hair, buccal pigmentation, postural hypotension,
dehydration, vitiligo etc.
• Blood cortisol level.
• The short ACTH stimulation test.
• Plasma ACTH level.
• Electrolytes and urea ( classically shows
hyponatremia, hyperkalemia and high
• Blood glucose levels may be low.
• Adrenal antibodies are present.
• Chest X-rays may show evidence of
• Serum aldosterone level is increased.
Long term treatment is replacement with
glucocorticoids and mineralcorticoids.
• In Addison’s disease, the following is
• a) hyperkalemia
• b) increase in ECF volume
• c) hyperglycemia
• d) high blood pressure
This syndrome is characterized by a clinical state
of increased free circulating glucocortcoid.
Adrenal cortex tumor that secretes excess
Anterior pituitary gland tumor that secretes
• Clinical features of Cushing’s syndrome:
Fat accumulates the face, neck and trunk.
Depression, insomnia, psychosis.
Thin skin, easy bruising.
Hair growth on face, acne.
Polyurea and polydipsia.
B. Signs :
Acne, thin skin, bruising, hirsutism, striae (purple),
Moon face, buffalo hump, central obesity
(pendulous abdomen, tomato head, potato body
and four match stick limbs).
Kyphosis, rib fractures.
Poor wound healing.
Proximal muscle wasting, proximal myopathy.
• Diagnosis: ( diagnosis of Cushing’s syndrome
is based on the following investigations).
Clinical features = buffalo hump, moon face,
Blood glucose level increases.
Blood cortisol level increases.
Urinary secretion of the 17 hydroxysteroids