Transcript Adrenal Disorders

Adrenal Disorders
Supervised by:
Dr.Azza Azzo
Dr. Rania Aljezani
Presented by:
Deema Alangari
Fatima AlHussain
Joza AlOtaiby
Rawan AlEnzi
¤ Physiology:
- The Adrenal gland are:
Triangle-shaped organs that weigh
approximately 4g .
- located:
Directly above the poles of the kidney.
- Composed of two physiologically
distinct organs:
The adrenal medulla and the adrenal
cortex.
Both of these endocrine organs are
responsible for producing substances that
aid the body in coping with stress.
The Adrenal medulla:
Represent the Innermost portion of the
adrenal gland.
Secretes: Epinephrine.
Norepinephrine.
All are related as Catecholamines.
The secretion of catecholamines is under
control of the sympathetic nervous system.
The Adrenal cortex:
represent outer portion, comprises 90% of
the adrenal gland.
Subdivided into three zones:
● The outer zona glomerulosa :
make up 15% of cortex.
● The medial zona fasciculata : make
up 75% of cortex.
● The inner zona reticularis : make
up 10% of cortex.
Synthesize and secrete :
● Glucocorticoids : e.g., cortisol , from the
zona fasciculata.
● Mineralocorticoids : aldosterone , from
the zona glomerulosa.
● Sex steroids : androgens and estrogens
from the zona reticularis.
► Normal physiological effect of
adrenaline and noradrenaline :
1. Glycogen broken down to glucose lead to
increase blood glucose level.
2. Increase blood pressure (due to
vasoconstriction of blood vessel )
3. Increase breathing grate (due to
bronchodilator effect of N)
4. Increase metabolic rate.
5.Change in blood flow patterns , leading to
increase digestive and kidney activity.
► Normal effect of cortisol:
Cortisol's most important job is to help the body
respond to stress. Among its other vital tasks,
cortisol.
- helps maintain blood pressure and cardiovascular
function.
- helps slow the immune system's inflammatory
response.
- helps balance the effects of insulin in breaking
down sugar for energy.
- helps regulate the metabolism of proteins,
carbohydrates, and fats.
- helps maintain proper arousal and sense of wellbeing.
► Normal effect of and aldosterone:
Aldosterone belongs to a class of
hormones called mineralocorticoids. It
helps maintain blood pressure and water
and salt balance in the body by helping
the kidney retain sodium and excrete
potassium.
¤ Metabolic effects of Glucocorticoids:
● Glucocorticoid excess causes
alteration in the following:
1. protein and carbohydrate metabolism.
2. Distribution of adipose tissue.
3. Electrolytes.
4. The immune system.
5. Gastric secretion.
6. Brain function.
7. Erythropoiesis.
8. suppresses inflammation.
Effect on protein:
Glucocorticoid have catabolic effect and
antianabolic effects on protein, causing:
Decrease in the ability of protein forming
cells to synthesize protein. As a
consequence, there is loss of protein from
tissue such as skin, muscles, bold vessels,
and bone.
● The skin:
The skin atrophies and break down easily;
wounds heal slowly.
Rapture of elastic fibers in the skin causes
purple stretch marks, or striae.
● The muscles:
- Muscles also atrophy and become
weak.
- Thinning of blood vessel walls and weakening
of perivascular supporting tissue result in
easy bruising. This condition can be severe
enough for petechiae or even large areas of
ecchymosis to appear under the cuff when
the patient's blood pressure is taken.
● The bone:
- There is loss of protein matrix of bone,
causing a condition known as osteoporosis ,
which occur most frequently in the spine,
causing vertebral collapse and resultant
back pain and loss of height.
Effect on carbohydrate :
Glucocorticoid stimulate gluconeogenesis and
interfere with the action of insulin in peripheral
cells. As a consequence, patients may develop
hyperglycemia.
● In person with an adequate insulinsecreting capacity:
The effect of glucocorticoids is countered by
increasing insulin secretion that subsequently
normalizes glucose tolerance.
● In patients with diminished insulinsecreting capacity:
They are unable to compensate.
Effect on the distribution of adipose tissue:
Accumulation of adipose tissue in the central area of
the body:
- truncal obesity.
- moon face: round face.
- buffalo hump: supraclavicular fossa fullness and
cervicodorsal hump.
The truncal obesity and thinning of the upper and lower
extremities as a result of muscle atrophy give patients
the classic cushingoid appearance.
Effect on serum electrolyte levels:
May cause sodium retention and potassium
waste, leading to edema hypokalemia, and
metabolic alkalosis.
Effect on gastric secretion:
Gastric secretory activity is increased because
steroids alter mucosal protective factors
lead to ulcer formation.
Effect on immune response:
Glucocorticoids can inhibit immune response.
- Immune responses are of two major types:
1. Production of humoral antibodies by B lymphocytes and
plasma cells following antigenic stimulation.
2. Depends on sensitized T lymphocytes-mediated reaction.
A] Impairment of the immunologic response can occur at each
of the stages of this response:
1. initial processing of antigens by cells of the
monocyte-macrophage system.
2. induction and proliferation of
immunocompetent lymphocytes and
release of cytokines.
3. antibody production.
4. the inflammatory reaction.
B] glucocorticoid also suppress delayed
hypersensitivity reactions.
C] The glucocorticoid-mediated inhibition of
cellular immunity is probably important in
suppressing transplant rejection.
On Cardiovascular :
Hypertension .
due to (increase aldosterone cause Na
and water retention and edema), increase
cardiac out put by effect of cortisone, and
Because sensitivity of blood vessel to
chatecolamine is increased.
Effect on brain function:
-emotional liability.
-euphoria.
-insomnia.
-episodes of transient depression.
Erythropoiesis :
-Involution of lymphoid tissue.
-stimulation of neutrophil release.
-enhancement of erythropoiesis.
Suppresses inflammatory response :
It is the most important and clinically useful
pharmacologic effect of glucocorticoids.
-inhibit hyperemia.
-extravasation of cells.
-cellular migration.
-capillary permeability.
-inhibit the release of vasoactivekinins.
-suppress phagocytosis.
By their effect on mast cells,
glucocorticoids inhibit histamine synthesis
and suppress the acute anaphylactic
reaction based on antibody-mediated
hypersensitivity.
Also decrease serum calcium levels →
hypocalcaemia.
҉ Regulated and stimulated by :
¤ Hypothalmic-Pitutary glandAdrenal Feedback system:
During stress, plasma Adrenocorticotropic
hormone (ACTH) is elevated, and then cortisol is
produced and released by the adrenal cortex.
ACTH is secreted by the anterior pituitary gland
under the regulatory control of corticotrophinreleasing factor (CRF), which is secreted by the
hypothalamus.
Catecholamines and vasopressin also simulate the
release of ACTH.
In stressful situations, ACTH secretion
increases to many time the basal rate and
increase cortisol production and
secretion.
As cortisol level increase in response to
ACTH stimulation. CRF release from the
hypothalamus is turned off. The decrease
in CRF then leads to a reduction in
further ACTH and cortisol secretion.
Conditions that Stimulate ACTH and
Cortisol Secretion
Cold exposure
Hypoglycemia
Pain
Infection
Anxiety
Trauma
Hemorrhage
Toxins
Exercise
Depression
Starvation
Alcoholism
¤ Circadian Rhythm:
It is factor which influences cortisol secretion.
This circadian, or diurnal, rhythm : is the cyclic
release of cortisol occurring throughout a 24-hr
period as a result of intrinsic endocrine function.
Minimal secretion of cortisol occurs just before and
in the initial hours of sleep; maximal secretion of
cortisol occurs just before and in the initial hours
of wakefulness. During the rest of the day;
intermittent secretion of cortisol occur.
Hyperfunction
of the adrenal
gland
ⱷ Cushing's Syndrome:
Cushing's syndrome may result from:
- long-term administration of pharmacologic
doses of glucocorticoids (iatrogenic).
-excessive cortisol secretion caused by a
disturbance in the hypothalamic-pituitaryadrenal axis (spontaneous).
● Iatrogenic Cushing's syndrome:
is seen in patients with conditions such as
rheumatoid arthritis, asthma, lymphoma, and
generized skin disorders who receive synthetic
glucocorticoids as anti-inflammatory agents.
● Spontaneous Cushing's syndrome:
Adrenocortical hyperfunction develops either as a
result of excessive stimulation by ACTH or as a
consequence of adrenal pathology leading to
abnormal production of cortisol.
Cushing's syndrome can be divided into
two types:
● ACTH- dependant:
Its etiologies based on chronic hypersecretion of
ACTH, account for approximately 80% of all cases
of spontaneous Cushing's syndrome.
Elevated ACTH levels lead to overstimulation of the
adrenal zona fasciculata and zona reticularis and
therefore, to increase secretion of cortisol and
androgens.
*ACTH-dependant causes include the
following:
1.pituitary microadenomas resulting in an
increased release of ACTH (Cushing's
disease).
2. ectopic, malignant ACTH-secreting tumors
(e.g., small cell carcinoma of the lung isletcell tumor, thymoma, and bronchial
adenoma).
3. ectopic CRF-secreting tumors.
● ACTH- independent:
ACTH- independent etiologies involve
cortisol secreting tumors, which lead to
elevated serum cortisol levels and
secondarily to suppressed ACTH release.
Accounting for fewer than 20% of patient
with Cushing's syndrome.
* ACTH- independent causes include the following:
1. nodular hyperplasia of the adrenal cortex.
2. adrenal cortical tumors. may be:
a- Benign (adenomas): may lead to severe
Cushing’s syndrome, but they usually
develop slowly, and symptoms may be
present for several years before the
diagnosis is finally made.
b- Malignant (carcinoma): develop rapidly
and may lead to metastasis and early
death.
3. ectopic production of cortisol.
N.B:
Female having 3.5 times higher risk than
males and having a propensity to
developing pituitary microadenmas
(Cushing's disease) as the cause of
Cushing syndrome.
Etiologies of Cushing’s Syndrome
Clinical Manifestation:
An overall change in appearance and
increased total body fat are classic initial
finding.
-Obesity is common, and fat is redistributed
to central areas of the body, resulting in
truncal or centripetal obesity with a
protuberant abdomen and wasted
extremities.
-moon faces: rounding of the face.
-buffalo hump.
-the skin of the patient is fine and
translucent (why?), because of atrophy of
the epidermal layer and connective tissue
beneath it.
-florid complexion.
-vascular striae.
-easy bruising and poor wound healing are
results of hypercortisolemic atrophy.
-Hyperpigmentation: from the stimulatory
action of cortisol on melanocytes may be
seen
-growth of lanugo facial hair.
-increase in androgen levels.
In female patients: Hirsutism (abnormal
growth of hair).
Acne.
Seborrhea.
Amenorrhea.
In male patients: Decrease in libodo.
Decrease in body
hair.
Testicular atrophy.
-On Muscle:
* muscles wasting and myopathy
(why?).
because of the catabolic effect of cortisol
on muscle tissue.
* Proximal muscle weakness.
* Primarily of the lower
extremities, is often exhibited
as
difficulty in climbing stairs
and
standing up from a sitting
position.
-effect on the metabolic functions of bone:
* inhibition of osteoblasts by cortisol may cause
osteopenia and ultimately osteoporosis.
* Hypercalciuria: result in kidney stone formation.
* In Adults: bone pain and fractures.
* In children: premature closure of the long
epiphyses, leading to stunted growth and short
stature.
-Hypokalemia.
-Psychiatric disturbance: include mood liability,
euphoria, increased anxiety, crying, insomnia,
and decreases in memory and
concentration.
-Immunosuppresion: which leads to a
predisposition for bacterial and
opportunistic infections ranging in severity
from fungal skin infections to Pneumocystis
carinii pneumonia and cryptococcal
meningitis.
Diagnosis:
1. 24-Hour Urinary Free cortisol Level (free scanning):
This is the most specific diagnostic test. The patient's urine is
collected over a24-hour period and tested for the amount of
cortisol.
Once Cushing's syndrome has been diagnosed, other tests are
used to find the exact location of the abnormality that leads
to excess cortisol production.
Normal value: 20 – 100 mg/24 hrs, when it is greater than 100
to 125 mg/24 hr. Cushing syndrome is likely.
2. Dexamethasone Suppression Test:
This test helps to distinguish patient with excess Production of ACTH
due to pituitary adenomas from those with ectopic ACTHproducing tumors.
Dexamethasone is a man-made (synthetic) steroid that is similar to
cortisol. It reduces ACTH release in normal people. Therefore,
taking dexamethasone should reduce ACTH levels and lead to
decreased cortisol levels.
Cushing syndrome related to ectopic ACTH-producing tumor: there
is no response.
Cushing syndrome caused by pituitary tumor (Cushing's disease)
there is a response to dexamethason suppression test.
3. CRH Stimulation Test:
This test helps to distinguish between
patients with Pituitary adenomas and
those with ectopic ACTH Syndrome or
cortisol-secreting adrenal tumors.
Patients are given an injection of CRH Rise
in blood levels of ACTH and cortisol in
patients With ectopic ACTH syndrome.
No response in patients with cortisolsecreting adrenal tumors.
4. Direct Visualization of the Endocrine
Glands (Radiological
Imaging):
Imaging test sreveal the size and shape of
the pituitary and adrenal glands and help
determine if a tumor is present.
Treatment:
-Surgical treatment.
-Medical treatment:
Medical treatment for Cushing's syndrome is
reserved for intractable cases of Cushing's syndrome
or situations in which there will be a delay in surgery.
Two types of medication are used:
1.medications that inhibit the pituitary secretion of
ACTH (e.g., Bromocriptine).
2.medications that inhibit the adrenocorticol
secretion of cortisol (e.g., Metyrapone).
ⱷ Aldosteronism:
Aldosteronism results from excessive
production of aldosterone, The
mineralocorticoid steroid hormone of the
adrenal cortex.
N.B:
Aldosterone enhances proximal renal tubule
reabsorption of sodium and causes
potassium and hydrogen ion excretion.
● The clinical consequence of
aldosterone excess:
-Sodium and water retention.
-expansion of the extracellular fluid volume.
-hypertension.
-hypernatremia.
-hypokalemia.
-metabolic alkalosis.
There are two types of aldosteronism:
● Primary Aldosteronism (Conn's
syndrome):
The excessive production of aldosterone occurs as
a result of tumor or hyperplasia of the adrenal
cortex.
Most aldosterone-secreting tumors are benign and
small – 0.5 to 2.0 cm.
It is a form of endocrine hypertension and probably
affects 1% to 2% of patients with hypertension.
● Secondary Aldosteronism:
Occurs in conditions in which afferent arteriolar
pressure in the renal glomerulus decreases,
leading to stimulation of the rennin-angotensin
system. Angotensin stimulates aldosterone
production.
It is seen in:
-Congestive heart failure.
-Cirrhosis of the liver.
-Kidney disease.
These conditions in which edema is prominent
clinical feature.
* Congestive heart failure exemplifies the way
secondary aldosteronism may develop (How?):
→ Patients in congestive heart failure cannot pump
blood normally and develop a fall in cardiac
output.
→ Perfusion pressure to the afferent arteriole of
the renal glomerulus decreases.
→ The fall in pressure is sensed by stretch
receptors in the juxtaglomerular apparatus.
→ Rennin is secreted in increased amounts.
→ Rennin activates angiotensin production.
→ Angiotensin stimulates aldosterone secretion by an
otherwise normal adrenal cortex.
→ The increased production of aldosterone promote
sodium and water reabsorption, expansion of the
extracellular fluid compartment, and possibly an
increase in afferent arteriolar pressure.
N.B.:
Secondary aldosteronism can also develop in conditions
in which a partial occlusion of the renal artery occurs,
leading to renal vascular hypertension.
Diagnosis:
Is based on:
1.the measurement of increased levels of
aldosterone in plasma.
2. the measurement of increased levels of
aldosterone in urine.
3.Special blood test called: plasma rennin activity
(PRA): is measured to distinguish between
primary aldosteronism (low PRA) and secondary
aldosteronism ( high PRA) .
4.Computered Tomography scanning and
Nuclear photoscanning: also help detect
and localize an adrenal lesion in patient
with primary aldosteronism. If a tumor
cannot be localized, samples of adrenal
venous blood may be obtained by
selective catheterization of the right and
left adrenal veins. A higher concentration
of aldosterone on the side suspected of
harboring a tumor helps confirm the
presence of the lesion.
Treatment:
Treatment of primary aldosteronism
includes unilateral adrenalectomy through
a laparoscopic approach, with resection of
the aldosterone-secreting hormone.
Patient with adrenal hyperplasia are treated
by the administration of aldosterone
antagonists such as sipronolactone.
ⱷ Syndromes of Androgen Excess:
Androgen Physiology:
Both men and women normally secrete
various androgen.
The three major types of androgen are:
1. dehyroepiandrosterone.
2. delta 4-androstenedione.
3. testosterone.
- the adrenal gland is the main source of it.
- its metabolite DHEA sulfate
Dehyroepiandroste - weak androgens.
- can be measured in the urine as 17rone (DHEA)
ketosteroids.
Delta 4androstenedione
Testosterone
- It is a stronger androgen product than
DHEA but weaker than testosterone.
- The adrenal cortex & ovary also produce
Delta 4-androstenedione.
- It is the most potent of the three androgen
compound.
- There are several source of testosterone
including in:
Adrenal cortex, the ovary, the testes ,and the
peripheral tissue.
- Testosterone circulates in the plasma
partially bound to a carrier protein: sex
hormone –binding globulin (SHBG),
a small fraction is unbound.
¤ Hirsutism :
One of the most common problem seen by
the endocrinologist among young women
is Hirsutism , which is usually a
manifestation of androgen excess.
● What is the hirsutism?
Hirsutism is excessive growth of body hair
in the female in a characteristic masculine
distribution over the facial, periareolar
,abdominal and sacral area.
It may be associated with baldness or
temporal recession of the hairline.
Hirsutism may be present alone or as a
part of the a virilizing syndrome.
Women with hirsutism usually have
abnormalities in testosterone secretion,
transport and metabolism.
For example; hirsute women have less
testosterone binding, higher free
testosterone level, and more active
metabolic clearance tests than women
without hirsutism.
Although in normal women testosterone is
extracted and metabolized almost
completely by the liver.
Hirsutism is seen in disorder such as
porphyria and congenital ectodermal
dysplasia or in areas of the body that have
been either immobilized or placed in a
body cast.
● Adrenal Virilism:
Virilism, excessive secretion of androgens from the
adrenal gland, is more commonly seen in females, with
hirsutism being the dominant feature.
Women who present with hirsutism also may have:
-voice deepening.
-increased muscle mass.
-menstrual abnormalities.
-clitoral enlargement.
While Virilism me be easy to diagnose based on clinical
symptoms, making the diagnosis on a biochemical
basis difficult.
The most common etiology of virilism involves one of
many possible congenital enzymes defects.
Depending on the enzyme deficiency, accumulation of a
variety of androgens, notably testosterone, can
develop.
Hirsutism, often without any other signs of virilism but
frequently accompanied by irregular or absent
menstrual period and acne, is a common clinical
entity and associated with polycystic ovary syndrome
(PCOS).
When hirsutism is present alone and without virilization
or menstrual irregularity, women are thought to have
simple or idiopathic hirsutism.
Differential diagnosis of androgen
Excess:
Five major categories of conditions are
associated with androgen excess:
1. Polycystic ovary syndrome ( PCOS).
2. Adrenocortical or ovarian tumors.
3. Late- onset or non classical adrenocortical
hyperplasia.
4. Simple or idiopathic hirsutism.
5. Miscellaneous states.
1. Polycystic ovary syndrome ( PCOS):
Hirsutism is frequently associated with infertility,
amenorrhea, obesity, and enlarged ovaries.
It have sustained elevations of serum luteinizing
hormone (LH).
In these patients testosterone production rates are
responsible for the manifestations of androgen execs.
The increased production of androgens in PCOS may
be secondary to the hyperinsulinemia that develops in
association with obesity.
The high insulin levels stimulate insulin-like growth
factor-1(IGF-1)concentration in the ovary and
cause increased androgen secretion.
PCOS may result from hypothalamic-pituitary
abnormalities affecting the cyclic release of
gonadotropins.
N.B.:
These change in gonadotropin secretion may lead
to anatomic changes in the ovary and stimulation
of ovarian androgen production .
2- Adrenocortical or ovarian tumors:
adrenocortical or ovarian tumors can be associated
with cortisol and produced with adrenogen
execs.
* Adrenocortical carcinomas secrete androgens
alone or in combination with cortisol and
produce either a pure virilizing syndrome or a
mixed Cushing’s virilizing syndrome.
* Ovarian tumors:
Such as arrhenoblastomas and hilus cell neoplasms,
are capable of secreting large amounts of
testosterone and producing virilization.
● Congenital Adrenal hyperplasia(CAH):
Is a condition in which there is an inborn
defect in one of the enzyme involved in
cortisol biosynthesis .
The most common type is a defect in 21hydroxylase , the adrenal cortex has an
impaired capacity to secrete cortisol.
The decrease in cortisol production causes an
increase in ACTH secretion in response to
the negative feedback activation of pituitary
function. ATCH stimulate the adrenal cortex
causing precursors of cortisol biosynthesis
to be shunted to the biosynthesis of
androgen.
When the fetus is exposed to increase
amounts of androgen, it undergoes change in
the development of the external genitalia.
This may create difficulties in sexual
identification of the new born.
For example; a female fetus with this defect
develops an enlargement of the clitoris and fusion
of the labia major. The genitalia then resemble
male external genitalia.
The syndrome of a masculinized genetically female
fetus caused by androgen excess in utero is called
female pseudohermaphroditism.
N.B.; manifestation of androgen excess in patients
with congenital adrenal hyperplasia can also
develop at puberty or
after puberty.
3- Late –onset or non classic CAH:
Is consequence of a milder form of
congenital adrenal hyperplasia with only
partial defects in 21-hyrdoxlase, 11-betahydroxlase,or 3-beta-ol-dehydrognase,
delta 4,5-isomerase.
Androgen Excess Differential Diagnosis
I. androgen excess of adrenocortical origin.
A) Cortisol excess: Cushing’s syndrome.
B) Androgen excess only.
1. prenatal : congenital adrenal hyperplasia(CAH).
2. postnatal :
a. late manifestation of CAH.
b. carcinoma.
3. pubertal or postpubertal.
a. hyperplasia , with or without polycystic ovaries.
b. carcinoma.
II. androgen excess of ovarian origin
A) NEOPLASMS: arrhenoblastoma ,adrenal rest cell neoplasms,
hilus cell neoplasm ,luteoma.
B) Hilus cell or leydig cell hyperplasia.
C) Polycystic ovary syndrome.
Continue: Androgen Excess Differential Diagnosis
III. simple or idiopathic hirsutism.
IV. miscellaneous cause.
A. endocrine
1. acromegaly
2. pregnancy
3. hypothyroidism
4. menopause
5.androgen therapy
6. inanition
B. Non endocrine
1. immobilization
2. body cast
3. porphria
4. congenital ectodermal dysplasia.
● Clinical and laboratory Evaluation of Hirsute
Women:
It is necessary to determine whether the hirsutism
is present by itself or accompanied by
manifestation of virilization.
It is also important to determine whether the
symptoms are those of androgen excess alone or
are accompanied by symptoms of cortisol excess.
A history of recent onset and rapid progression of
excessive hair growth frequently suggests a
malignancy as the source of excessive androgen
production.
Tests to document excessive
androgen production include:
● Measurement of blood levels of total and free
testosterone ,DHEA , androstenedione .
● When PCOS is suspected , measurement of
serum LH and glucose and insulin levels is helpful.
● Patient suspected of non classical CAH should
have , in addition , measurement of serum 17
alpha-hydroxyprogesterone and 17 alphahydroxypregnenolone before and after
stimulation with corticotrophin.
● In the presence of an enzyme defect, this
stimulation result in an exaggerated rise
of these steroid precursors and helps
confirm the diagnosis.
● Patient suspected of an adrenal or
ovarian androgen secreting tumor should
undergo a pelvic examination abdominal
and pelvic CT scan, MRI, or ultrasound.
ⱷ Pheochromocytoma:
Pheos mean dusky, Chromo mean color, Cytoma
mean tumor refers to color the tumor cells
acquire when stained by chromium salts.
It is a rare cause of secondary hypertension.
It is an adrenal medullary or sympathetic chain
(paraganglioma) tumor that releases excessive
amounts of catecholamines (epinephrine,
norepinephrine and dopamine) in sustained or
intermittent manner.
N.B.:
Pheochromocytoma affect 0.1% to 0.5% of the hypertensive
population and may have fatal outcome if undiagnosed or
untreated.
Pheochromocytoma occurs equally in men and women and has
a peak incidence between age 30 and 50.
90% of these tumors are derived from adrenal medullary
chromaffin cells, and 10% are extraadrenal, located in the
retropertioneal area (organs of Zuckerkandl), celiac and
mesentric ganglia, and urinary bladder.
Pheochromocytoma are usually benign (95% of cases), but they
may be malignant and present with distant metastases.
Clinical manifestation:
Clinical manifestation of these tumors are related to the
release of catecholamine.
1. The most prominent feature is hypertension that may be
paroxysmal (45% of cases) or sustained.
N.B.:
Patients with paroxysmal symptom develop acute episodes of
sever hypertension (250/140 mm Hg)lasting minutes to
hours. The episodes may be triggered by exercise, ingestion
of tyrosine-containing foods (red wine, aged cheese, yogurt ),
caffeine-containing foods, abdominal palpation, or induction
of anesthesia.
2. Patients remain normotensive between
episodes.
- headaches on the top of their head.
- palpitations.
- pallor.
- diaphoresis.
- dysrhythmias.
* Patients with sustained hypertension may
also show variability in their high-blood
pressure readings and complain of headaches
and irregular heartbeat.
3.Patients present with symptoms of
orthostatic hypotension, especially if the
tumor secretes significant amounts of
dopamine.
Diagnosis:
1. The biochemical evaluation of patients suspected
of a Pheochromocytoma.
Consists of measurement of plasma or urinary
levels of : epinephrine, norepinephrine, and their
metabolites metanephrine and normetanephrine.
Because normal adrenal secretion of epinephrine
and norepinephrine may vary, distinction between
physiologic and pathologic hypersecretory states
may be difficult with a single determination of
catecholamine levels.
Norepinephrine can increase with a change from the
recumbent to the upright position.
Catecholamines are also increased with an acute myocardial
infarction, volume depletion, hypothyroidism, and other
physical or emotional stress.
Peripheral vasodilators, cocaine, phenoxybenzamine can
increase catecholamine release.
Insulin-induced hypoglycemia can evoke major increases in
epinephrine and small increases in norepinephrine.
Drugs such as clonidine, decrease plasma norepinephrine levels.
2. Basal plasma catecholamine levels should be
obtained with the patient resting in the
supine position for at least 30 minutes.
Normal levels:
- epinephrine, range from o to 100 pg/ml.
- norepinephrine, 0 to 500 pg/ml.
- dopamine, 0 to 100 pg/ml.
Markedly increased levels (epinephrine more
than 500 pg/ml and norepinephrine greater
than 1500 pg/ml) are virtually diagnostic of
pheochromocytoma.
3. Basal urinary catecholamines should be
collected for 12 hours during the night.
Normal levels:
- epinephrine, 0 to 20 mg/day.
- norepinephrine, 0 to 100 mg/day.
- metanephrines, 0 to 300 mg/day.
- normetanephrines, 50 to 800 mg/day.
- vanillyl mandelic acid (VMA), 0 to 7 mg/day.
Patients with pheochromocytoma have high
urinary catecholamine levels.
4. In borderline cases, a clonidine suppression test may
help differentiate normal subjects from patients with
a pheochromocytoma (How?)
- 0.3 mg of clonidine, is administered orally after two
baseline blood samples for epinephrine and
norepinephrine are obtained.
- Plasma epinephrine and norepinephrine samples are
repeated 3 hours after clonidine administration.
Patients with a pheochromocytoma fail to suppress
catecholamine secretion, whereas clonidine will
restore normal levels of catecholamines in other
hyperadrenergic states.
Treatment:
1. Surgical resection of the pheochromocytoma and
exploration of the retroperitoneal space for
paraganglia-derived tumors.
2. Patients' blood pressure should be stabilized
preoperatively by:
- alpha adrenergic blocking agents. such as
phenoxybenzarnine.
- Beta-blockers, such as propranolol, when needed.
- Phenoxybenzamine is also used as medical treatment
to block catecholamine effects in patients with
malignant, unresectable pheochromocytomas.
Hypofunction
of the adrenal
gland
ⱷ Addison’s Disease:
Definition:
It results from primary or secondary causes.
- Primary adrenocortical insufficiency (Addison's disease):
Result from destruction of the adrenal cortex.
* Tuberculosis used to be the most frequent cause of Addison's
disease
- Secondary adrenocortical insufficiency:
Due to deficient pituitary ACTH secretion causing atrophy of
the adrenal cortex.
Etiology:
Approximately 80% of primary adrenocortical
insufficiency is now idiopathic .
The remaining 20% of Addison's disease occurs as a
complication of Tuberculosis or in rare situation,
is due to:
- cancer infections ( bacterial or fungal ).
- trauma.
- hemorrhagic disorders.
- congenital adrenal hypoplasia (autoimmune
destruction of the adrenal gland).
Adrenal insufficiency in patients with acquired
immune deficiency syndrome (AIDS) occur rarely
and is thought to be due to:
- disseminated infection.
- Neoplasm.
- autoimmune process.
- changes associated with chronic disease.
- malnutrition.
The common cause of secondary adrenocortical
insufficiency is steroid withdrawal in a patient
with adrenal atrophy due to exogenous
glucocorticoid therapy.
Pathogenesis:
In addition to primary or secondary causes ,
adrenocortical insufficiency can also be acute or
chronic
A) chronic adrenocortical insufficiency:
- When Addison's disease occurs as a result of
gradual destruction of the adrenal gland , chronic
adrenal insufficiency is manifested .
- Patients of this disease have normal basal cortisol
secretion but may have difficulty in increasing
cortisol secretion with stress .
N.B.:
Over time , even basal cortisol secretion
becomes inadequate , and clinical
manifestations of adrenocortical
insufficiency become evident.
However , without an acute stressful event ,
chronic adrenal insufficiency will usually
go unnoticed because of the vaguse
symptoms of the disease.
B) Acute adrenocortical insufficiency :
- When adrenal need, generated by stress
of surgery, trauma, or infection, exceeds
the glands capacity for cortisol
production.
- When 90% or more of the adrenal cortex
is nonfunctioning and is usually
accompanied by elevated ACTH levels.
Clinical Manifestation :
Adrenocortical insufficiency is not manifested until
more than 90% of both adrenal cortices are lost .
● Hyperpigmentation of the skin and mucous
membranes is usually the hallmark characteristic that
prompts the physician to test for adrenal insufficiency.
- It is most pronounced in sunexpsed areas of the body
and at pressure point but also occurs on palmer
creases, nail beds, the tongue, the nipples, the navel,
and the perivaginal and perianal mucosa.
- Present in 92% of patients.
- Is caused by increased melanocyte-stimulating
hormone and B-lipotropin serum levels , which
accompany increased ACTH levels.
-Vitiligo also occur but at a much lower incidence of
approximately 4 to 17 %.
● gastrointestinal symptoms such as nausea, abdominal
discomphort , diarrhea, vomiting are warning signs
that may signal progressive adrenal insufficiency and
impending crisis.
● Addisonian Crisis :
Acute addisonian crisis (apoplexy) results
when a patient with undiagnosed
Addison's disease becomes stresses or is
exposed to a stressful event such as
trauma, infection, surgery, or hemorrhage
.
Signs and Symptoms :
- Anorexia develops and is accompanied by
nausea and vomiting .This leads to severe
dehydration and hemodynamic instability .
- Fever, with or without a concurrent infection
.
- Abdominal pain and tenderness may confuse
the diagnosis as one of acute abdominal
event.
- Weakness , fatigue .
- Confusion .
- Coma and shock .
Diagnosis :
* The diagnosis of adrenal insufficiency is made
by specific laboratory tests.
* Patients with primary adrenal insufficiency
have decreased cortisol and aldosterone but
high ACTH and rennin levels.
* The intravenous infusion of synthetic ACTH
fails to elicit a rise in cortisol level.
* Because of aldosterone deficiency,
electrolyte levels show:
-Hyponatremia.
-Hyperkalemia.
-Metabolic acidosis.
-Esinophilia.
-Lymphocytosis.
-Hypoglycemia.
-Increase blood urea nitrogen levels.
* Patient with adrenal insufficiency secondary
to ACTH deficiency have low levels of both
cortisol and ACTH .
References:
Phathophysiology, ch.61
Text book of Therapeutic, ch.16
Pharmacotherapy, ch. 74
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