ADRENOCORTCAL

HORMONES
 Adrenal Glands
The two adrenal glands, each of which weighs about 4
grams, lie at the superior poles of the two kidneys.

Each gland is composed of two distinct parts, the adrenal medulla

and the adrenal cortex.
The adrenal medulla, the central 20 per cent of the gland, is
functionally related to the sympathetic nervous system; it secretes
the hormones epinephrine and norepinephrine in response to
sympathetic stimulation.

The adrenal cortex secretes an entirely different group of

hormones, called corticosteroids. These hormones are all synthesized
from the steroid cholesterol.
 Adrenal
capsule - 15Cortex
1.The zona glomerulosa - just underneath the
% - aldosterone - enzyme aldosterone
synthase - controlled by the ECF concentrations of
angiotensin II and potassium

2.The zona fasciculata – middle layer – 75 % -

glucocorticoids cortisol and corticosterone - small
amounts of adrenal androgens and estrogens -
controlled by the hypothalamic-pituitary axis via ACTH

3.The zona reticularis - deep layer of the cortex - the

adrenal androgens dehydroepiandrosterone (DHEA)
and androstenedione - small amounts of estrogens
and some glucocorticoids - ACTH
 Glucocorticoid
•Cortisol (very potent, accounts for about 95 per cent
s
of all glucocorticoid activity)
•Corticosterone (provides about 4 per cent of total
glucocorticoid activity, but much less potent than
cortisol)

• Cortisone (synthetic, almost as potent as cortisol)

•Prednisone (synthetic, four times as potent as
cortisol)
•Methylprednisone (synthetic, five times as potent as
cortisol)
•Dexamethasone (synthetic, 30 times as potent as
cortisol)
 Glucocorticoid
Stimulation of Gluconeogenesis - formation of
s
carbohydrate from proteins and some other substances by
liver

1. Cortisol increases the enzymes required to

convert amino acids into glucose in the liver cells

2. Cortisol causes mobilization of amino acids from

the extra hepatic tissues mainly from muscle

marked increase in glycogen storage in the liver cells. This

effect of cortisol allows other glycolytic hormones, such as
epinephrine and glucagon, to mobilize glucose in times of
need, such as between meals
 Carbohydrate
Metabolism
Decreased Glucose Utilization by Cells –
glucocorticoids depress the oxidation of NADH to form
NAD+. Because NADH must be oxidized to allow
glycolysis.

high levels of glucocorticoid reduce the sensitivity of

many tissues, especially skeletal muscle and adipose
tissue, to the stimulatory effects of insulin on glucose
uptake and utilization - adrenal diabetes
 Protein Metabolism
reduction of the protein stores in essentially
all body cells except those of the liver –
muscle weakness
This is caused by both decreased protein synthesis
and increased catabolism of protein - decreased
amino acid transport into extrahepatic tissues -
cortisol mobilizes amino acids from the nonhepatic
tissues

enhance amino acid transport into liver cells and

enhance the liver enzymes required protein
- Cortisol Increases Liver and Plasma
synthesis for
Proteins
 Fat Metabolism
Mobilization of Fatty Acids - increases the

diminishedconcentration of free into

transport of glucose fattythe
acidsfatincells:
the plasma,
alpha -
glycerophosphate, which is derived from glucose, is
required for both deposition and maintenance of
triglycerideswhich also increases
in these cells, and their
in its utilization
absence the for fat
energy.
cells
begin to release fatty acids.
Cortisol also seems to have a direct effect to
Obesity - excess deposition of fat in the chest and head
regions of the body, giving a buffalo-like torso and a
rounded “moon
enhance face”
the-oxidation
excess stimulation of food
of fatty acids in the intake,
cells
with fat being generated in some tissues of the body more
rapidly than it is mobilized and oxidized
 Anti-inflammatory Effects
1.Cortisol stabilizes the lysosomal membranes -
proteolytic enzymes that are released by damaged
cells to cause inflammation, which are mainly stored
in the lysosomes, are released in greatly decreased
quantity

2.Cortisol decreases the permeability of the

Capillaries - prevents loss of plasma into the tissues.

3.Cortisol decreases both migration of WBC into the

inflamed area and phagocytosis of the damaged cells -
cortisol diminishes the formation of PGs and LTs that
increase vasodilation, capillary permeability, and
mobility of WBC .
 Anti-inflammatory Effects
4.Cortisol suppresses the immune system, causing T
lymphocyte reproduction to decrease markedly - reduced
amounts of T cells and antibodies in the inflamed area
decrease the tissue reactions

5.Cortisol reduces fever mainly because it reduces the

release of IL-1 from WBC, which is one of the principal
excitants to the hypothalamic temperature control system -
decreased temperature reduces vasodilation

Rate of healing is greater - mobilization of amino acids and

use of these to repair the damaged tissues – extra glucose –
fatty acids - Resolution of Inflammation

Rheumatoid arthritis, rheumatic fever and acute

glomerulonephritis
 Anti-inflammatory Effects
Cortisol Blocks the Inflammatory Response to Allergic
Reactions - cortisol effectively prevents shock or
death in anaphylaxis

Cortisol decreases the number of eosinophils and

lymphocytes in the blood - atrophy of all the
lymphoid tissue throughout the body - fulminating
infection and death

Prevents immunological rejection of transplanted

hearts, kidneys, and other tissues
Circadian Rhythm
Hypoadrenalism - Addison’s Disease
primary atrophy of the adrenal cortices – autoimmunity (80%)

tuberculous destruction of the adrenal glands or invasion of the

adrenal cortices by cancer

Mineralocorticoid Deficiency - greatly decreased ECF volume -

hyponatremia, hyperkalemia and mild acidosis - CO decreases,
and the patient dies in shock

Glucocorticoid Deficiency – cant maintain normal blood glucose

concentration between meals - reduces the mobilization of both
proteins and fats from the tissues - highly susceptible to stress
and infection

Melanin Pigmentation - mucous membranes and thin skin (lips,

nipples)
 Treatmen
small quantities of mineralocorticoids and glucocorticoids
are administered daily
t
Addisonian Crisis
In a person with Addison’s disease, the output of glucocorticoids
does not increase during stress.

whenever different types of trauma, disease, or other stresses,

such as surgical operations, appear, a person is likely to have an
acute need for excessive amounts of glucocorticoids and often
must be given 10 or more times the normal quantities of
glucocorticoids to prevent death.

This critical need for extra glucocorticoids and the associated

severe debility in times of stress is called an addisonian crisis

Adrenal crisis – tapering dose always

Hyperadrenalism - Cushing’s
Syndrome
abnormal excess secretion of cortisol & androgens

(1) adenomas of the anterior pituitary that secrete large

amounts of ACTH, which then causes adrenal
hyperplasia and excess cortisol secretion;
(2) abnormal function of the hypothalamus that causes
high levels of CRH, which stimulates excess ACTH
release;
(3) “ectopic secretion” of ACTH by a tumor elsewhere in
the body, such as an abdominal carcinoma;
(4) adenomas of the adrenal cortex – Reduced ACTH

When Cushing’s syndrome is secondary to excess secretion

of ACTH by the anterior pituitary, this is referred to
as
Cushing’s disease
 Dexamethasone
In patients who have overproduction of ACTH due to
Test
an ACTH-secreting pituitary adenoma or to
hypothalamic-pituitary dysfunction, even large doses
of dexamethasone usually do not suppress ACTH
secretion.

In patients with primary adrenal overproduction of

cortisol usually have low or undetectable levels of
ACTH.

Cushing’s syndrome can also occur when large

amounts of glucocorticoids are administered over
prolonged periods for therapeutic purposes –
Rheumatoid Arthritis
Cushing’s syndrome
mobilization of fat from the lower part of the
body, with concomitant extra deposition of fat in
the thoracic and upper abdominal regions, giving
rise to a buffalo torso – Buffalo hump

Edematous appearance of the face (Moon Face) –

acne & hirsutism – Hypertension

Hyperglycemia - ↓ protein except liver (Plasma

proteins) – muscle weakness - suppressed immune
system - large purplish striae - severe
 Treatmen
t
Hypertrophied pituitary glands or tumors – Surgical removal
or irradiation

Removal
When surgery is an adrenal tumor –
not possible;
Drugs that block steroidogenesis -
ketoconazole and aminoglutethimide
Adrenalectomy metyrapone,
Drugs that inhibit ACTH secretion - serotonin antagonists
and GABA-transaminase inhibitors

Bilateral partial (or even total) adrenalectomy, followed by

administration of adrenal steroids to make up for any
insufficiency