Physiology: - The Adrenal gland are: Triangle-shaped organs
that weigh approximately 4g. - located: Directly above the poles of
the kidney.
Slide 3
- 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.
Slide 4
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.
Slide 5
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.
Slide 6
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.
Slide 7
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.
Slide 8
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 well-
being.
Slide 9
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.
Slide 10
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.
Slide 11
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.
Slide 12
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.
Slide 13
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.
Slide 14
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.
Slide 15
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 insulin- secreting
capacity: The effect of glucocorticoids is countered by increasing
insulin secretion that subsequently normalizes glucose tolerance.
In patients with diminished insulin- secreting capacity: They are
unable to compensate.
Slide 16
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.
Slide 17
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.
Slide 18
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.
Slide 19
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.
Slide 20
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.
Slide 21
Effect on brain function: -emotional liability. -euphoria.
-insomnia. -episodes of transient depression. Erythropoiesis :
-Involution of lymphoid tissue. -stimulation of neutrophil release.
-enhancement of erythropoiesis.
Slide 22
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.
Slide 23
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.
Slide 24
Regulated and stimulated by :
Slide 25
Hypothalmic-Pitutary gland- Adrenal 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 corticotrophin- releasing factor (CRF), which is
secreted by the hypothalamus. Catecholamines and vasopressin also
simulate the release of ACTH.
Slide 26
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.
Slide 27
Conditions that Stimulate ACTH and Cortisol Secretion
Hypoglycemia Cold exposure InfectionPain TraumaAnxiety
ToxinsHemorrhage DepressionExercise AlcoholismStarvation
Slide 28
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.
Slide 29
Slide 30
Hyperfunction of the adrenal gland
Slide 31
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-pituitary- adrenal axis (spontaneous).
Slide 32
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.
Slide 33
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.
Slide 34
*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 islet- cell tumor, thymoma, and
bronchial adenoma). 3. ectopic CRF-secreting tumors.
Slide 35
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.
Slide 36
* 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 Cushings 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.
Slide 37
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.
Slide 38
Etiologies of Cushings Syndrome
Slide 39
Slide 40
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.
Slide 41
-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.
Slide 42
-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
Slide 43
-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.
Slide 44
-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.
Slide 45
-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.
Slide 46
-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.
Slide 47
Slide 48
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.
Slide 49
2. Dexamethasone Suppression Test: This test helps to
distinguish patient with excess Production of ACTH due to pituitary
adenomas from those with ectopic ACTH- producing 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.
Slide 50
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
cortisol- secreting adrenal tumors.
Slide 51
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.
Slide 52
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).
Slide 53
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.
Slide 54
The clinical consequence of aldosterone excess: -Sodium and
water retention. -expansion of the extracellular fluid volume.
-hypertension. -hypernatremia. -hypokalemia. -metabolic
alkalosis.
Slide 55
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.
Slide 56
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.
Slide 57
* 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.
Slide 58
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.
Slide 59
Slide 60
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).
Slide 61
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.
Slide 62
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.
Slide 63
Syndromes of Androgen Excess: Androgen Physiology: Both men and
women normally secrete various androgen.
Slide 64
The three major types of androgen are: 1.
dehyroepiandrosterone. 2. delta 4-androstenedione. 3.
testosterone.
Slide 65
- the adrenal gland is the main source of it. - its metabolite
DHEA sulfate - weak androgens. - can be measured in the urine as
17- ketosteroids. Dehyroepiandroste rone (DHEA) - It is a stronger
androgen product than DHEA but weaker than testosterone. - The
adrenal cortex & ovary also produce Delta 4-androstenedione.
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. Testosterone
Slide 66
Hirsutism : One of the most common problem seen by the
endocrinologist among young women is Hirsutism, which is usually a
manifestation of androgen excess.
Slide 67
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.
Slide 68
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.
Slide 69
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.
Slide 70
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.
Slide 71
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.
Slide 72
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.
Slide 73
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.
Slide 74
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.
Slide 75
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 Cushings virilizing syndrome. * Ovarian tumors:
Such as arrhenoblastomas and hilus cell neoplasms, are capable of
secreting large amounts of testosterone and producing
virilization.
Slide 76
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 21- hydroxylase,
the adrenal cortex has an impaired capacity to secrete
cortisol.
Slide 77
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.
Slide 78
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.
Slide 79
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-beta- hydroxlase,or 3-beta-ol-dehydrognase, delta
4,5-isomerase.
Slide 80
Androgen Excess Differential Diagnosis I. androgen excess of
adrenocortical origin. A) Cortisol excess: Cushings 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.
Slide 81
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.
Slide 82
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.
Slide 83
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 alpha- hydroxypregnenolone before
and after stimulation with corticotrophin.
Slide 84
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.
Slide 85
Slide 86
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.
Slide 87
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.
Slide 88
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.
Slide 89
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.
Slide 90
3.Patients present with symptoms of orthostatic hypotension,
especially if the tumor secretes significant amounts of
dopamine.
Slide 91
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.
Slide 92
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.
Slide 93
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.
Slide 94
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.
Slide 95
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.
Slide 96
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.
Slide 97
Hypofunction of the adrenal gland
Slide 98
Addisons 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.
Slide 99
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).
Slide 100
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.
Slide 101
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.
Slide 102
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.
Slide 103
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.
Slide 104
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.
Slide 105
- 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.
Slide 106
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.
Slide 107
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.
Slide 108
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.
Slide 109
* 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.
Slide 110
References: Phathophysiology, ch.61 Text book of Therapeutic,
ch.16 Pharmacotherapy, ch. 74 www.e-medicin.com