Chapter 60

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Chapter 60

Drugs for Disorders of the Adrenal Cortex

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Adrenal Cortex Hormones Affect multiple processes

Maintenance of glucose availability Regulation of water and electrolyte balance Development of sex characteristics Life-preserving responses to stress

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Physiology of the Adrenocortical Hormones

Three classes of steroid hormones from the adrenal cortex:1. Glucocorticoids2. Mineralocorticoids3. Androgens

Two most familiar forms of adrenocortical dysfunction:1. Adrenal hormone excess

• Cushing’s syndrome2. Adrenal hormone deficiency

• Addison’s disease

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Glucocorticoids: Physiologic Effects Physiologic effects (occur at low levels)

Carbohydrate metabolism Protein metabolism Fat metabolism Cardiovascular system Skeletal muscle Central nervous system Stress Respiratory system in neonates

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Fig. 60–2. Negative feedback regulation of glucocorticoid synthesis and secretion.

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Mineralocorticoids Influence renal processing of sodium,

potassium, and hydrogen Aldosterone

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 Androstenedione

Minimal physiologic effects at normal levels In excess (congenital adrenal hyperplasia)

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Adrenal Hormone Excess Cushing’s syndrome

Causes• Hypersecretion of adrenocorticotropic hormone (ACTH)• Hypersecretion of glucocorticoids• Administering glucocorticoids in large doses

Clinical presentation• Obesity• Hyperglycemia• Glycosuria• Hypertension• Fluid and electrolyte disturbances

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Adrenal Hormone Excess Cushing’s syndrome (cont’d)

Treatment• Carcinoma/adenoma: surgical removal of adrenal gland• Replacement therapy with glucocorticoids and

mineralocorticoids for bilateral adrenalectomy• Drugs are adjunct for surgical treatment

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Primary Hyperaldosteronism Excessive secretion of aldosterone Causes

Hypokalemia, metabolic alkalosis, hypertension Treatment

Based on underlying cause Surgery or aldosterone antagonist

(spironolactone)

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Adrenal Hormone Insufficiency General therapeutic considerations

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

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Adrenal Hormone Insufficiency Addison’s disease (primary adrenocortical

insufficiency) 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

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Adrenal Hormone Insufficiency 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)

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Adrenal Hormone Insufficiency Acute adrenal insufficiency (adrenal crisis)

Can lead to death Clinical presentation

Hypotension Dehydration Weakness Lethargy GI symptoms (vomiting and diarrhea)

Causes Adrenal failure Pituitary failure Inadequate doses of corticosteroids or abrupt withdrawal

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Adrenal Hormone Insufficiency Acute adrenal insufficiency (cont’d)

Treatment• Rapid replacement of fluid, salt, and glucocorticoids

(hydrocortisone)• Glucose: normal saline with dextrose

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Adrenal Hormone Insufficiency Congenital adrenal hyperplasia

Clinical presentation and causes Treatment—glucocorticoids employed—

hydrocortisone, dexamethasone, prednisone Screening

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Agents for Replacement Therapy in Adrenocortical Insufficiency

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 Synthetic steroid with structure identical to

cortisol Therapeutic uses

Adrenal insufficiency Allergic reactions to inflammation Cancer

Adverse effects of high-dose therapy Adrenal suppression Cushing’s syndrome

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Fludrocortisone (Florinef) Potent mineralocorticoid Therapeutic uses

Addison’s disease Primary hypoaldosteronism Congenital adrenal hyperplasia

Adverse effects Hypertension Edema Cardiac enlargement Hypokalemia

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Diagnostic Testing ofAdrenocortical Function

ACTH is used primarily for diagnostic tests Cosyntropin

• Synthetic polypeptide whose structure corresponds to the first 24 amino acids of ACTH

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Dexamethasone Synthetic steroid

Primarily glucocorticoid properties; very little mineralocorticoid activity

Overnight dexamethasone test to diagnose Cushing’s syndrome

Prolonged dexamethasone suppression test