Disorders Of Adrenal Glands
Dr. Wael H.Mansy, MD
Assistant Professor
College of Pharmacy
King Saud University
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Adrenal Glands
The adrenal glands are
small, triangular structures
that lie on top of the
kidneys.
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Adrenal Glands
 Anatomically, the adrenal glands may be divided
into two parts:
1. The adrenal medulla, and,
2.
The adrenal cortex.
 The adrenal medulla contains cells that secrete:
the catecholamines, epinephrine and
norepinephrine.
 Cells of the adrenal cortex secrete the
Glucocorticoids (mainly cortisol), the
Mineralcorticoids (mainly aldosterone) and
some testosterone.
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Physiologic functions of the adrenal
hormones
Catecholamines
Epinephrine and norepinephrine Involved in:
• the “fight or flight response”:
• Interact with α and β receptors in the body
• Increase heart and respiratory rate
• Increase energy availability; stimulate
glycogenolysis in the liver as well as plasma
levels of free fatty acids
• Reduce gastrointestinal activity
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Physiologic functions of the adrenal
hormones
Adrenal Cortex
I) Glucocorticoids:
Cortisol, corticosterone, cortisol???
•Stimulate the synthesis and storage of glycogen
•Increase gluconeogenesis and blood glucose levels
•Exert catabolic effects in muscle and fat tissue
•Anti-inflammatory action; used clinically as anti-inflammatory agents
II) Mineralcorticoids:
Aldosterone
• act on the distal tubules and collecting ducts of the kidney to
increase reabsorption of sodium
•Increase plasma volume
•Increase renal excretion of potassium
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Adrenal Cortex: I) Glucocorticoids
Control of Cortisol Secretion: Feedback Loops
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Congenital Adrenal Hypoplasia
• An autosomal recessive disorder in which the enzymes
necessary for cortisol synthesis are deficient.
• Lack of cortisol-negative feedback on the pituitary gland
leads to excess ACTH production, which in turn increases
the synthesis and release of androgens from the adrenal
cortex.
• Aldosterone production may also be altered depending on
the specific enzyme(s) lacking.
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Congenital Adrenal Hypoplasia
Manifestations
• Masculinization of the female external genitals
(pseudohemaphroditism).
• Short stature due to premature fusion of the epiphyseal growth
plate in the long bones.
• With certain forms of CAH, a lack of aldosterone production may
lead to significant “salt wasting” (sodium losses).
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Congenital Adrenal Hypoplasia
Treatment
• Administration of cortisone/hydrocortisone will reduce ACTH
levels and block the subsequent production of excess androgens.
• Serum electrolyte levels should be closely monitored and
corrected, particularly in the salt-wasting form of CAH.
• Reconstructive surgery of the genitals may be necessary in
females to alter the obvious male characteristics.
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Addison’s disease
• A primary condition associated with atrophy of the adrenal
glands.
• The majority of cases arise from autoimmune destruction of the
adrenal glands.
• Some cases may occur as a result of adrenal gland injury as a
result of infection or tumors.
• Decreased production of cortisol, aldosterone and androgens
from the adrenal glands.
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Addison’s disease
Manifestations
• Weakness and fatigue.
• Increased pigmentation of the skin due to an ACTH-induced
increase in Melanocyte (skin pigment cell) activity.
• Weight loss, anorexia, hypometabolism, cold intolerance.
•
Cardiovascular
changes:
Hypotension
up
to
orthostatic
hypotension.
• Changes in electroencephalogram and mental function.
• Although androgen production from the adrenal glands is
reduced, androgen production from other sites in the body (testis)
is sufficient to maintain normal sexual function and development11
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Addison’s disease
Treatment
As the manifestations of Addison’s disease are due to deficiency
of all three hormone groups produced by the adrenal gland
(glucocorticoids, mineralcorticoids and androgens), Treatment will
be
Lifelong
replacement
therapy
with
glucocorticoids
(cortisone/hydrocortisone) and mineralcorticoids (aldosterone).
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Adrenal Cortex: I) Glucocorticoids
Hyposecretion of Adrenal Glands
Adrenal Crisis
An episode of severe hypotension, vascular
collapse, acute renal failure and hypothermia
caused by a combined lack of cortisol and
aldosterone. It may be precipitated by infection,
trauma
and
dehydration
in
individuals
with
Addison’s disease and can be life-threatening.
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Adrenal Cortex: I) Glucocorticoids
Hypersecretion of Adrenal Glands
Cushing's disease
• Characterized by excess circulating levels of cortisol.
• May be caused by excess ACTH secretion due to
pituitary tumors or a tumor of the adrenal gland itself. In
rare instances, ACTH or cortisol-producing tumors may
occur in the body outside the pituitary or adrenal glands
themselves.
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Adrenal Cortex: I) Glucocorticoids
Hypersecretion of Adrenal Glands
Cushing's disease
Manifestations:
• Characteristic “moon face” and “buffalo hump” patterns of fat
distribution.
• Glucose intolerance and possible diabetes mellitus.
• Thin skin, poor wound healing, impaired immune function.
• Hypertension.
• Muscle weakness and wasting.
• Reduced bone density, hypercalciuria with possible development
of renal calculi.
• Alterations in mental function and personality.
• Increased androgen levels in females with possible “virilization.”
• Mortality is approximately 50% within 5 years if left untreated.
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The most common symptom of Cushing's
syndrome is sudden weight gain, usually
manifested by central obesity.
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Adrenal Cortex: I) Glucocorticoids
Hypersecretion of Adrenal Glands
Cushing's disease
Treatment:
• Surgical removal of tumors.
• Radiation therapy.
• Chemotherapy if tumor is inoperable. Mitotane is a
compound that is structurally similar to the insecticide
DDT. It is used because of its selective toxicity for cells of
the adrenal cortex to treat tumors arising in this tissue
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Adrenal Medulla:
Pheochromocytoma
• A tumor (usually benign) that arises in the chromaffin
cells
of
the
adrenal
medulla
that
produce
the
catecholamines.
• Symptoms are those of excess catecholamine
production and can be life-threatening.
• Excess catecholamine production may be continual or
occur in episodes (“bursts”).
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Adrenal Medulla:
Pheochromocytoma
Manifestations:
Hypertension
Tachycardia
Severe headache
Nausea and vomiting
Excess sweating (diaphoresis)
Palpitations
Anxiety
Risk of stroke due to marked hypertension
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Types of Pheochromocytoma
Paroxysmal Type:
*The tumor secretion occurs in bouts.
*Manifestations occurs only during bouts.
*In-between bouts the patient is completely
normal.
Sustained Type:
*The tumor secretion is continuous.
*The manifestations begins with the start of tumor
secretion,
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Adrenal Medulla:
Pheochromocytoma
Treatment:
β-Blocking and α-blocking drugs to blunt
catecholamine effects
Surgical removal of tumor
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