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Chapter 60
Drugs for Disorders of the
Adrenal Cortex
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Adrenal Cortex Hormones
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Affect multiple processes
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Maintenance of glucose availability
Regulation of water and electrolyte balance
Development of sex characteristics
Life-preserving responses to stress
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Physiology of the Adrenocortical
Hormones
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Three classes of steroid hormones from the adrenal
cortex:
1.
2.
3.
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Glucocorticoids
Mineralocorticoids
Androgens
Two most familiar forms of adrenocortical
dysfunction:
1.
2.
Adrenal hormone excess
• Cushing’s syndrome
Adrenal hormone deficiency
• Addison’s disease
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Glucocorticoids: Physiologic Effects
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Physiologic effects (occur at low levels)
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Carbohydrate metabolism
Protein metabolism
Fat metabolism
Cardiovascular system
Skeletal muscle
Central nervous system
Stress
Respiratory system in neonates
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fig. 60–2. Negative feedback regulation of glucocorticoid synthesis and secretion.
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Mineralocorticoids
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Influence renal processing of sodium,
potassium, and hydrogen
Aldosterone
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Promotes sodium and potassium hemostasis
Maintains intravascular volume
Harmful cardiovascular effects with high levels
Regulated by renin-angiotensin-aldosterone
system (RAAS)
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Adrenal Androgens
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Androstenedione
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Minimal physiologic effects at normal levels
In excess (congenital adrenal hyperplasia)
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Adrenal Hormone Excess
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Cushing’s syndrome
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Causes
• Hypersecretion of adrenocorticotropic hormone (ACTH)
• Hypersecretion of glucocorticoids
• Administering glucocorticoids in large doses
 Clinical presentation
• Obesity
• Hyperglycemia
• Glycosuria
• Hypertension
• Fluid and electrolyte disturbances
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenal Hormone Excess
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Cushing’s syndrome (cont’d)
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Treatment
• Carcinoma/adenoma: surgical removal of adrenal gland
• Replacement therapy with glucocorticoids and
mineralocorticoids for bilateral adrenalectomy
• Drugs are adjunct for surgical treatment
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Primary Hyperaldosteronism
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Excessive secretion of aldosterone
Causes
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Hypokalemia, metabolic alkalosis, hypertension
Treatment
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Based on underlying cause
Surgery or aldosterone antagonist
(spironolactone)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenal Hormone Insufficiency
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General therapeutic considerations
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Replacement therapy with glucocorticoids
• Should mimic normal patterns of corticosteroid secretion
• 2/3 in the morning and 1/3 in the afternoon
• Doses for endocrine disorders are much smaller than for
nonendocrine disorders
• Increase dosage in times of stress
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenal Hormone Insufficiency
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Addison’s disease (primary adrenocortical
insufficiency)
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Clinical presentation and causes
• Weakness and hypotension
• Emaciation
• Hypoglycemia, hyperkalemia, hyponatremia
• Increased pigmentation of skin and mucous membranes
Treatment
• Replacement therapy with adrenocorticoids
• Hydrocortisone is the drug of choice

Both glucocorticoid and mineralocorticoid
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenal Hormone Insufficiency
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Secondary adrenocortical insufficiency results
from decreased secretion of ACTH
Tertiary insufficiency results from decreased
secretion of CRH
In both cases, adrenal secretion of glucocorticoids
is diminished, whereas secretion of
mineralocorticoids is usually normal
Treatment consists of replacement therapy with a
glucocorticoid (eg, hydrocortisone)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenal Hormone Insufficiency
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Acute adrenal insufficiency (adrenal crisis)
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Clinical presentation
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Can lead to death
Hypotension
Dehydration
Weakness
Lethargy
GI symptoms (vomiting and diarrhea)
Causes
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Adrenal failure
Pituitary failure
Inadequate doses of corticosteroids or abrupt withdrawal
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Adrenal Hormone Insufficiency
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Acute adrenal insufficiency (cont’d)
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Treatment
• Rapid replacement of fluid, salt, and glucocorticoids
(hydrocortisone)
• Glucose: normal saline with dextrose
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Adrenal Hormone Insufficiency
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Congenital adrenal hyperplasia
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Clinical presentation and causes
Treatment—glucocorticoids employed—
hydrocortisone, dexamethasone, prednisone
Screening
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Agents for Replacement Therapy in
Adrenocortical Insufficiency
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Require replacement therapy with
corticosteroids
Glucocorticoid is always required
Some patients require a mineralocorticoid
as well
The principal glucocorticoids employed are
hydrocortisone, dexamethasone, and
prednisone
Fludrocortisone is the only mineralocorticoid
available
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Hydrocortisone
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Synthetic steroid with structure identical to
cortisol
Therapeutic uses
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Adrenal insufficiency
Allergic reactions to inflammation
Cancer
Adverse effects of high-dose therapy
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Adrenal suppression
Cushing’s syndrome
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
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Fludrocortisone (Florinef)
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Potent mineralocorticoid
Therapeutic uses
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Addison’s disease
Primary hypoaldosteronism
Congenital adrenal hyperplasia
Adverse effects
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Hypertension
Edema
Cardiac enlargement
Hypokalemia
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Diagnostic Testing of
Adrenocortical Function
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ACTH is used primarily for diagnostic tests
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Cosyntropin
• Synthetic polypeptide whose structure corresponds to the
first 24 amino acids of ACTH
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Dexamethasone
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Synthetic steroid
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Primarily glucocorticoid properties; very little
mineralocorticoid activity
Overnight dexamethasone test to diagnose
Cushing’s syndrome
Prolonged dexamethasone suppression test
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