ADRENOCORTICAL HORMONES
ANATOMY
• The adrenal glands are small, yellowish organs that rest on
the upper poles of the kidneys in the Gerota fascia.
• The right adrenal gland is pyramidal, whereas the left one
is more crescentic, extending toward the hilum of the
kidney.
• At age 1 year, each adrenal gland weighs approximately 1 g,
and this increases with age to a final weight of 4-5 g.
• The arterial blood supply comes from 3 sources, with
branches arising from the inferior phrenic artery, the renal
artery, and the aorta.
• Venous drainage flows directly into the inferior vena cava
on the right side and into the left renal vein on the left side.
• Lymphatics drain medially to the aortic nodes.
• Each adrenal gland is composed of two
distinct parts:
• The adrenal cortex and the adrenal medulla.
• The cortex is divided into three zones.
• From exterior to interior, these are
• The zona glomerulosa,
• The zona fasciculata, and
• The zona reticularis.
Adrenal Cortex
• The adult cortex
composed of 3 zones
– Glomerulosa
– Fasciculata
– Reticularis
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Adrenal Cortex Hormones
4
PRODUCTION..
EMBRYOLOGY
• First detected at 6 weeks' gestation, the adrenal cortex is
derived from the mesoderm of the posterior abdominal
wall.
• Steroid secretion from the fetal cortex begins shortly
thereafter.
• Adult-type zona glomerulosa and fasciculata are detected
in fetal life but make up only a small proportion of the
gland, and the zona reticularis is not present at all.
• The fetal cortex predominates throughout fetal life.
• The adrenal medulla is of ectodermal origin, arising from
neural crest cells that migrate to the medial aspect of the
developing cortex.
• The fetal adrenal gland is relatively large.
• At 4 months' gestation, it is four times the size
of the kidney; however, at birth, it is a third of
the size of the kidney.
• This occurs because of the rapid regression of
the fetal cortex at birth.
• It disappears almost completely by age 1 year;
by age 4-5 years, the permanent adult-type
adrenal cortex has fully developed.
• Anatomic anomalies of the adrenal gland may
occur.
• Because the development of the adrenals is
closely associated with that of the kidneys,
agenesis of an adrenal gland is usually associated
with ipsilateral agenesis of the kidney, and fused
adrenal glands (whereby the two glands join
across the midline posterior to the aorta) are also
associated with a fused kidney.
• Adrenal hypoplasia occurs in the following two
forms:
• Hypoplasia or absence of the fetal cortex with
a poorly formed medulla
• Disorganized fetal cortex and medulla with no
permanent cortex present
PHYSIOLOGY
• Adrenal cortex
• The adrenal cortex secretes the following
three types of hormones:
• Mineralocorticoids (the most important of
which is aldosterone), which are secreted by
the zona glomerulosa
• Glucocorticoids (predominantly cortisol),
which are secreted by the zona fasciculata
and, to a lesser extent, the zona reticularis
• Adrenal androgen (mainly
dehydroepiandrosterone [DHEA]), which is
predominantly secreted by the zona
reticularis, with small quantities released from
the zona fasciculata
• All adrenocortical hormones are steroid
compounds derived from cholesterol
Structure
Derivative of cholesterol
Have 3 cyclohexyl rings( A, B, C)
One cyclopentyl ring (D)
18
19
2
10
A
4
12
5
17
16
14
9
B
13
D
C
1
3
11
8
15
7
6
Cyclopentanoperhydrophenanthrene
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Adrenal Cortex Hormones
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Synthesis
Cholesterol
ACTH
Ang II
pregnenolone
Cortisol &
sex steroids
progesterone
Deoxycortico
sterone
11 hydroxylase
Cortisone
18hydroxycortico
sterone
Aldosterone
synthatase
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Aldosterone
synthatase,
Ang II
Aldosterone
Adrenal Cortex Hormones
13
Synthesis
Acetate
cholesterol
pregnenolone
17-OHpregnenolone
progesterone
17-OHprogesterone
Aldosterone
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Cortisol
Adrenal Cortex Hormones
Androgen
14
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Adrenal Cortex Hormones
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Cortisol
• Cortisol binds to proteins in the blood, mainly cortisolbinding globulin or transcortin.
• More than 90% of cortisol is transported in the blood
in this bound form.
• In contrast, only 50% of aldosterone is bound to
protein in the blood.
• All adrenocortical steroids are degraded in the liver and
predominantly conjugated to glucuronides, with lesser
amounts of sulfates formed.
• About 75% of these degradation products are excreted
in the urine, and the rest is excreted in the stool by
means of the bile.
Glucocorticoids
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Adrenal Cortex Hormones
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Functions of Glucocorticoids
• Affect metabolic systems for utilizing
– Proteins
– Carbohydrates
– Fats
• 95% of glucocorticoid activity of adrenal
cortex result from
– Cortisol (hydrocortisone)
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Mechanism of Action
• Multiple effects of
glucocorticoids
triggered by
– Binding to intracellular
receptors which
– Interact with specific
regulatory DNA
sequences
• Glucocorticoids Response
Element
Textbook of Medical Physiology:
By Guyton
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Adrenal Cortex Hormones
21
Mechanism of Action
• Induce or repress gene
transcription
• Leads to Increased or
decreased
– Formation of mRNA
• Alters synthesis of
enzymes
• Alter cell functions
Textbook of Medical Physiology:
By Guyton
17-Nov-21
Adrenal Cortex Hormones
22
• Glucocorticoids
• Approximately 95% of glucocorticoid activity comes
from cortisol, with corticosterone, a glucocorticoid less
potent than cortisol, making up the rest.
• Normal cortisol concentration in the blood averages 12
μg/dL, with a secretory rate averaging 15-20 mg/day.
• Cortisol release is almost entirely controlled by the
secretion of ACTH by the anterior pituitary gland,
which is controlled by corticotropin-releasing hormone
(CRH) secreted by the hypothalamus
• In normal situations, CRH, ACTH, and cortisol
secretory rates demonstrate a circadian
rhythm, with a spike in the early morning.
• Various stresses stimulate increased ACTH
and, thus, cortisol secretion.
• A –ve feedback effect of cortisol on the
anterior pituitary and the hypothalamus help
control these increases and regulate plasma
cortisol concentrations.
Glucocorticoids
• Produced from zona fasciculata
• Cortisol (very potent, accounts for about 95 per cent of
all glucocorticoid activity)
• Corticosterone (provides about 4 per cent of total
glucocorticoid activity, but much less potent than
cortisol)
• Hydrocortisone (synthetic, almost as potent as cortisol)
• Prednisone (synthetic, 4 times as potent as cortisol)
• Methylprednisone (synthetic, 5 times as potent as
cortisol)
• Dexamethasone (synthetic, 30 times as potent as
cortisol)
• Adrenal hormones are bound to plasma proteins:
90-95% of cortisol in plasma binds to a globulin
called cortisol-binding globulin or transcortin & to
a lesser extent albumin
• Slows elimination giving it a half of 60-90
minutes. While only 60% of aldosterone binds to
plasma proteins (40% free form) having a half life
of 20 minutes.
• Binding serves as a reservoir to lessen rapid
fluctuations in free hormone concentration & to
ensure uniform distribution to the tissues.
Functions of glucocorticoids
• 95% of glucocorticoid activity results from
cortisol, also known as hydrocortisone.
• In addition, there is a small but significant
amount of glucocorticoid activity is provided
by corticosterone.
Carbohydrate metabolism
• 1.Stimulation of Gluconeogenesis (formation of
carbohydrates from proteins and some other
substances) by the liver which is increased as much
as 6- to 10- fold. This results mainly from two effects:
• Increases the enzymes required to convert amino
acids into glucose in the liver cells.
• Cause mobilization of amino acids from the
extrahepatic tissues mainly from muscle. Results in
more amino acids becoming available to enter into
the gluconeogenesis process in liver thereby
promoting increased formation of glucose.
• With increased gluconeogenesis, there is
increased glycogen storage in the liver cells
allowing other glycolytic hormones, such as
epinephrine and glucagon, to mobilize glucose in
times of need, such as between meals.
• 2.Decreased Glucose Utilization by Cells.
• Cause of this is unknown, but believed that
somewhere between the point of entry of
glucose into the cells and its final degradation,
cortisol directly delays the rate of glucose
utilization.
• 3. Elevated Blood Glucose Concentration and “Adrenal
Diabetes.”
• Increased rate of gluconeogenesis and reduction in
glucose utilization by the cells causes the blood glucose
concentration to rise which in turn stimulates insulin
secretion.
• However, the levels are not as effective in maintaining
plasma glucose as they are under normal conditions
• High levels of glucocorticoid somehow reduce the
sensitivity of many tissues, especially skeletal muscle
and adipose tissue, to the stimulatory effects of insulin
on glucose uptake and utilization.
Protein metabolism
• 1.Reduction in Cellular Protein –
• Reduces the protein stores in all cells except liver cells.
• Caused by both decreased protein synthesis and
increased catabolism of protein already in the cells.
• Effect results from depressed formation of RNA and
subsequent protein synthesis in many extrahepatic
tissues, especially in muscle and lymphoid tissue.
• In excessive levels cortisol, the muscles can become so
weak that the person cannot rise from the squatting
position.
• 2. Cortisol Increases Liver and Plasma Proteins.
• With the reduced proteins elsewhere in the body,
liver proteins become enhanced and plasma
proteins increased.
• This results from the effect of cortisol to enhance
amino acid transport into liver cells (but not into
most other cells) and to enhance the liver
enzymes required for protein synthesis.
Fat metabolism
• 1.Mobilization of Fatty Acids from adipose tissue.
• This increases the concentration of free fatty acids in the
plasma, which also increases their utilization for energy.
• 2. Obesity Caused by Excess Cortisol –
• Moderate degree of fatty acid mobilization from adipose
tissue may cause people with excess cortisol secretion to
develop a peculiar type of obesity (excess deposition of fat
in the chest and head regions of the body, giving a buffalolike torso and a rounded “moon face”).
• Although the cause is unknown, it has been suggested that
this obesity results from excess stimulation of food intake,
with fat being generated in some tissues of the body more
rapidly than it is mobilized and oxidized.
Cortisol is Important in Resisting Stress
and Inflammation
• In almost any type of stress, whether physical or neurogenic there is
an immediate and marked increase in ACTH secretion, followed
within minutes by greatly increased secretion of cortisol.
• Some of the different types of stress that increase cortisol release
are the following:
• Trauma of almost any type
• Infection
• Intense heat or cold
• Injection of norepinephrine and other sympathomimetic drugs
• Surgery
• Injection of necrotizing substances beneath the skin
• Restraining an animal so that it cannot move
• Almost any debilitating disease
• Significance of this increase is unknown.
• However, a possibility is that the
glucocorticoids cause rapid mobilization of
amino acids and fats from their cellular stores,
making them immediately available both for
energy and for synthesis of other compounds,
including glucose, needed by the different
tissues of the body.
Anti-inflammatory Effects of High
Levels of Cortisol
• When large amounts of cortisol are secreted or
injected into a person, the cortisol has two basic
antiinflammatory effects:
• (1) it can block the early stages of the inflammation
process before
inflammation even begins, or
• (2) if inflammation has already begun, it causes rapid
resolution of the inflammation and increased rapidity
of healing.
• These is because cortisol Prevents the Development of
Inflammation by Stabilizing Lysosomes and by Other
Effects.
Cortisol has the following effects in
preventing inflammation:
• 1. Cortisol stabilizes the lysosomal membranes.
• Important because it is makes it more difficult for the
membranes of the intracellular lysosomes to rupture.
• As such, there is decreased release of proteolytic
enzymes that are released by damaged cells to cause
inflammation (which are mainly stored in the
lysosomes).
• 2. Cortisol decreases the permeability of the
capillaries, probably as a secondary effect of the
reduced release of proteolytic enzymes. This prevents
loss of plasma into the tissues.
• 3. Cortisol decreases both migration of white
blood cells into the inflamed area and
phagocytosis of the damaged cells.
• These effects are due to diminished formation
of prostaglandins and leukotrienes (which
normally cause vasodilation, increased
capillary permeability, and increased mobility
of white blood cells).
• 4. Cortisol suppresses the immune system, causing
lymphocyte reproduction to decrease markedly.
• The T lymphocytes are especially suppressed. In turn,
reduced amounts of T cells and antibodies in the
inflamed area lessen the tissue reactions that would
otherwise promote the inflammation process.
• 5. Cortisol attenuates fever mainly because it reduces
the release of interleukin-1 from the white blood cells,
which is one of the principal excitants to the
hypothalamic temperature control system.
• The decreased temperature in turn reduces the degree
of vasodilation.
Cortisol causes resolution of
inflammation
• Even after inflammation has become well
established, the administration of cortisol can
often reduce inflammation within hours to a few
days.
• The immediate effect is to block most of the
factors that are promoting the inflammation.
• In addition, the rate of healing is enhanced.
• This effect of cortisol plays a major role in
combating certain types of diseases, such as
rheumatoid arthritis, rheumatic fever, and acute
glomerulonephritis.
• All these diseases are characterized by severe
local inflammation, and the harmful effects on
the body are caused mainly by the inflammation
itself and not by other aspects of the disease.
• On administration of cortisol or other
glucocorticoids the the inflammation begins to
subside within 24 hours.
• Glucocorticoids may not correct the basic disease
condition but by merely preventing the damaging
effects of the inflammatory response, this alone
can often be a lifesaving measure.
Other effects
• Cortisol Blocks the Inflammatory Response to Allergic
Reactions
• Effect on Blood Cells and on Immunity in Infectious
Diseases - Cortisol decreases the number of eosinophils
and lymphocytes in the blood; this effect begins within a
few minutes after the injection of cortisol and becomes
marked within a few hours.
• Administration of large doses of cortisol causes significant
atrophy of all the lymphoid tissue throughout the body,
which in turn decreases the output of both T cells and
antibodies from the lymphoid tissue.
• This results in decreased immunity to all for
almost all foreign invaders
• This ability to suppress immunity makes
glucocorticoids useful drugs in preventing
immunological rejection of transplanted
hearts, kidneys, and other tissues.
• Cortisol also increases the production of red
blood cells (via unclear mechanisms).
• Excess cortisol will result in polycythemia and
conversely decreased cortisol results in
anemia
Cellular mechanism of cortisol
• Is lipid soluble and will diffuse through the cell
membrane.
• In cytoplasm, binds with its protein receptor in the
cytoplasm
• Hormone-receptor complex then interacts with specific
regulatory DNA sequences, called glucocorticoid
response elements, to induce or repress gene
transcription.
• Will then increase or decrease transcription of many
genes to alter synthesis of mRNA for the proteins that
mediate their multiple physiologic effects.
• Thus, most of the metabolic effects will not be
immediate but require 45 to 60 minutes for
proteins to be synthesized, and up to several
hours or days to fully develop.
• However, especially at high concentrations,
they may also have some rapid nongenomic
effects on cell membrane ion transport that
may contribute to their therapeutic benefits.
CORTISOL ON PROTEINS
• PRINCIPAL ACTION
REDUCTION OF PROTEIN STORES IN ALL
TISSUES EXCEPT THE LIVER
BY
Depressing formation of RNA in most tissues
and stimulating protein catabolism
CORTISOL ON PROTEINS..
• IN EXCESS
• MUSCLE WEAKNESS WHERE ONE CANNOT
RISE FROM A SQUATTING POSITION
• THIS IS DUE TO INCREASED MOBILISATION OF
AMINO ACIDS FROM EXTRAHEPATIC TISSUES
DECREASING PROTEIN STORES
CORTISOL ON PROTEINS..
• IN EXCESS..
INCREASED PLASMA CONCENTRATION OF
AMINO ACIDS LEADS TO
1. INCREASED AMINO ACID DEAMINATION BY
LIVER
2. INCREASED LIVER PROTEIN SYNTHESIS
3. INCREASED PLASMA PROTEINS FORMATION
BY THE LIVER
4. INCREASED GLUCONEOGENESIS
CORTISOL ON FATS
• INCREASES
 Mobilisation of fats from adipose tissue
 Free fatty acids in the plasma
Increasing utilisation
 FATTY ACID OXIDATION IN CELLS
 THIS ENHANCES UTILISATION OF FATS INSTEAD OF
GLUCOSE IN TIMES OF STARVATION AND OTHER
STRESSES
RELEASE
REGULATION OF CORTISOL
SECRETION
LEVELS
Mineralocorticoids
• Aldosterone accounts for 90% of
mineralocorticoid activity, with some activity
contributed by deoxycorticosterone,
corticosterone, and cortisol.
• The normal conc’n of aldosterone in the blood
ranges from 2-16 ng/dL supine and 5-41 ng/dL
upright, although the concentration exhibits
diurnal variation, and the secretory rate is
generally 150-250 mcg/d.
Effects
• Promotes Na reabsorption and K+ excretion by
the renal tubular epithelial cells of the
collecting and distal tubules.
• As Na+ is reabsorbed, water follows passively,
leading to an increase in the extracellular fluid
volume with little change in the plasma Na
conc’n.
• Persistently elevated extracellular fluid
volumes cause hypertension.
• This helps minimize further increases in
extracellular fluid volume by causing a
pressure diuresis in the kidney, a phenomenon
known as aldosterone escape.
• Without aldosterone, the kidney loses
excessive amounts of sodium and,
consequently, water, leading to severe
dehydration
• As Na+ is actively reabsorbed, K+ is excreted.
• Imbalances in aldosterone thus lead to
hypokalemia and muscle weakness if levels are
increased and to hyperkalemia with cardiac
toxicity if levels are decreased.
• In addition to Na being exchanged for K at the
renal tubules, H+ is also exchanged, although to a
much lesser extent.
• As such, with aldosterone excess, mild metabolic
alkalosis may develop.
• Also has smaller but similar effect on the
sweat glands and salivary glands.
• Stimulates NaCl reabsorption and K secretion
in the excretory ducts, which helps prevent
excessive salivation and conserve body salt in
hot climates.
• Also affects Na absorption in the intestine,
especially the colon.
• Deficiency may cause a watery diarrhea from
the unabsorbed sodium and water.
• Most important factor affecting secretion is
the the renin-angiotensin system and changes
in the plasma potassium concentration, as
follows
1. Activation of the renin-angiotensin system –
• The JGA senses decreased blood flow to the
kidney secondary to hypovolemia, hypotension,
or renal artery stenosis and releases renin
• Renin is an enzyme that activates
angiotensinogen to release angiotensin I;
• In the lungs, ACE converts angiotensin I to
angiotensin II, a potent vasoconstrictor and
stimulator of aldosterone release by the adrenal
gland
2. ECF potassium conc’n –
• Increases in the plasma K+ conc’n stimulate
the release of aldosterone to encourage
potassium excretion by the kidney
3. ECF Na+ Conc’n
• Decreases in plasma Na+ conc’n also stimulate
aldosterone release
4. Adrenocorticotropic hormone (ACTH)
secretion –
• ACTH secreted by the anterior pituitary
primarily affects release of glucocorticoids by
the adrenal but, to a lesser extent, also
stimulates aldosterone release
Adrenal Androgens
• The adrenal cortex continually secretes several
male sex hormones which include
• Dihdroepiandrosterone (DHEA)
• DHEA sulfate (DHEAS),
• Androstenedione, and
• 11-hydroxyandrostenedione,
• Also small quantities of the female sex
hormones progesterone and estrogen.
• Most of the effects result from extra-adrenal
conversion of the androgens to testosterone.
• All have weak effects, but they likely play a role in
early development of the male sex organs in
childhood, and they have an important role in
women during pubarche.
• ACTH has a definite stimulatory effect on
androgen release by the adrenal
• Therefore, secretion of these hormones parallels
that of cortisol.
Adrenal Medulla
• The adrenal medulla is a completely different
entity.
• Epinephrine (80%)
• Norepinephrine (20%), and
• Minimal amounts of dopamine,
• are secreted into the bloodstream due to
direct stimulation by acetylcholine release
from sympathetic nerves.
• Preganglionic sympathetic nerve fibers pass
from the intermediolateral horn cells of the
spinal cord through the sympathetic chains
and splanchnic nerves, without synapsing, into
the adrenal medulla.
• These hormones are responsible for an
increase in cardiac output and vascular
resistance and for all the physiologic
characteristics of the stress response.
Adrenal Pathology
•
•
•
•
•
Glucocorticoid excess
Mineralocorticoid excess
Androgen excess
Catecholamine excess
Adrenal insufficiency
EFFECTS OF EXCESS PRODUCTION
• Glucocorticoid excess or Cushing syndrome
• The clinical findings associated with excess
cortisol secretion most commonly include
• Obesity with moonlike face (the obesity is due to
excess deposition of fats in chest and head
regions )
• Growth failure,
• Hirsutism, and
• Acne.
Cushing’s syndrome
• Corticosteroid dependent cushings syndrome
due to excess stimulation by ACTH
• Could be due to CRH excess from an extrapituitary tissue eg small cell lung calcinoma.
• Could be due to excess secretion of CRH by
pituitary corticotroph tumors and is the most
common form of the syndrome
CUSHING’S SYNDROME...
CUSHING’S SYNDROME
CUSHING’S SYNDROME
CUSHING’S SYNDROME
CUSHING’S SYNDROME
CUSHING’S SYNDROME
• Other findings include
• hypertension, muscle weakness, osteoporosis,
glucose intolerance, easy bruising,
yperpigmentation and thin skin, menstrual
irregularities, and psychiatric disturbances.
• Patients with cortisol excess also have impaired
wound healing and an increased susceptibility to
infection.
• The differential diagnosis of Cushing syndrome is
as follows:
• Use of exogenous steroids
• ACTH-independent causes - Adrenal nodular
hyperplasia, adrenocortical adenoma,
adrenocortical carcinoma
• ACTH-dependent causes - Pituitary adenoma
(Cushing disease), ectopic ACTH (non pituitary
tumours producing ACTH) or CRH production
from tumors (eg, pancreatic tumor)
Mineralocorticoid excess
• Presenting features of mineralocorticoid excess
include
• Hypertension,
• Headache,
• Tachycardia,
• Others are fatigue, proximal muscle weakness,
polyuria, and polydipsia.
• The differential diagnosis of hyperaldosteronism
is as follows:
• Primary –
• Idiopathic adrenal nodular hyperplasia (idiopathic
hyperaldosteronism), glucocorticoid-suppressible
hyperaldosteronism, adrenocortical adenoma,
adrenocortical carcinoma
• Secondary –
• Elevated renin secretion secondary to renal artery
stenosis, a renin-producing tumor, congestive
heart failure, and Bartter syndrome (ie,
juxtaglomerular hyperplasia)
Primary hyperaldosteronism
•
•
•
•
•
•
Characterized by
Elevated plasma aldosterone,
low plasma renin levels,
hypokalemia, and
hypertension,
Rare in children where, unlike in adults, most
common cause is bilateral adrenal hyperplasia
• Bilateral adrenal hyperplasia as a cause of
hyperaldosteronism occurs in nodular adrenal
hyperplasia and in a unique autosomal dominant
condition called glucocorticoid-suppressible
hyper-aldosteronism.
• This has all of the clinical and biochemical
features noted in other causes of primary
hyperaldosteronism but demonstrates complete
and rapid suppression of aldosterone secretion
by administration of dexamethasone.
Androgen excess
• The predominant clinical feature of
hyperandrogenism in the newborn girl is
ambiguous genitalia.
• In the older child or adolescent, signs and
symptoms include
• pseudoprecocious puberty in boys and
• hirsutism, acne, clitoromegaly, deepening of
voice, and oligomenorrhea in girls.
• In both sexes, linear growth and skeletal
maturation (ie, bone age) are accelerated.
Causes
1. Use of exogenous anabolic steroids
2. Adrenal causes –
• Congenital adrenal hyperplasia , Adrenocortical
adenoma, adrenocortical carcinoma,
3. Extra-adrenal causes –
• Polycystic ovary, ovarian tumors, testicular
tumors (most commonly Leydig cell tumors),
adrenal hyperplasia secondary to a pituitary
adenoma or ectopic secretion of ACTH or CRH,
hyperprolactinemia, acromegaly
Catecholamine excess
• The clinical manifestations include
• hypertension, tachycardia, arrhythmias,
headache, fatigue, visual blurring, sweating
and heat intolerance, weight loss, abdominal
pain, and polyuria and polydipsia.
• These symptoms should prompt biochemical
testing to confirm excess catecholamine
secretion characteristic of
pheochromocytoma.
• Pheochromocytomas are rare tumors that
arise from the neural crest–derived
chromaffin cells found in the adrenal medulla
and sympathetic ganglia.
Adrenal Insufficiency
• May be acute or chronic.
• Chronic adrenal insufficiency may be primary,
secondary, or tertiary.
• Acute adrenal insufficiency results when an
acute stress is superimposed on chronic
adrenal insufficiency of any type.
• Symptoms of chronic adrenal insufficiency may
be explained by the lack of adrenal hormones
and by the unopposed secretion of ACTH.
• Hypotension, fatigue, weight loss, anorexia,
nausea, vomiting, abdominal pain, salt craving,
hypoglycemia, and syncope can occur.
• Skin and mucous membrane hyperpigmentation
resulting from unopposed secretion of ACTH and
melanocyte-stimulating hormone.
• Hyponatremia, along with hyperkalemia, is
sometimes observed due to chronic
insufficiency of aldosterone.
• Diagnosis should not be based on the
presence or absence of these abnormalities.
• The loss of secondary sex characteristics is
seen only in women with the disease.
Acute Adrenal Insufficiency
• Is a medical emergency and must be identified
and promptly treated.
• Hallmarks of acute adrenal insufficiency are
circulatory collapse with abdominal pain that
can simulate an acute abdomen.
• Profound hypoglycemia, elevated core
temperature, and potentially cardiac
dysrhythmias are also observed.
Chronic adrenal insufficiency
• Primary insufficiency
• results when the adrenal glands themselves are
destroyed or infiltrated
• Causes
• Congenital adrenal hyperplasia,
• bilateral hemorrhage
• Severe meningococcal infection or other severe,
bacterial infection), TB, HIV, histoplasmosis, and
infiltrative diseases (eg, sarcoidosis).
• Autoimmune destruction of the adrenal glands is
referred to as Addison disease.
Secondary insufficiency
• Results from diminished release of ACTH from the
pituitary.
Causes
• Trauma,
• Pituitary tumors, and
• Pituitary hemorrhage (Sheehan syndrome- a
condition that affecting women who lose a lifethreatening amount of blood in childbirth or who
have severe low blood pressure during or after
childbirth. The lack of oxygen from above causes
damage to the pituitary gland).
Tertiary Insufficiency
• Results from suppression of the hypothalamicpituitary-adrenal axis.
• Observed with the long-term administration
of exogenous steroids.
• Important distinguishing feature of tertiary
adrenal insufficiency is that adrenal medullary
and androgen-secreting functions are
preserved.