Nursing Pharmacology Chapter 28: Physiology and Pharmacology: Adrenocorticosteroids / Adrenocortical Antagonists
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Bilateral adrenal hyperplasia due to pituitary adenoma (basophilic tumor)
About 20 to 25 percent of Cushing's syndrome patients have adrenal neoplasm
ACTH Hypersecretion
Other Causes
Adrenal tumors
Nodular adrenal hyperplasia-- causes:
Familial autoimmune (children/young adults)-- pigmented multinodular cortical dysplasia
Hypersensitivity to gastric inhibitory peptide {increased peptide receptor expression in adrenal cortex}
Ectopic, nonendocrine tumors that produce ACTH
Three times greater in women
Most frequent age of onset: 30s to 40s
Manifestations include:
Abnormal fat deposition
Truncal obesity-- mesenteric bed
Rounded face ("moon facies")
Interscapular area ("buffalo hump")
Hirsuitism
Effects of protein loss
Muscle wasting
Skin thinning
Striae: secondary to weakening/rupture of dermal collagen fibers
Poor wound healing
Bruising
Osteoporosis
Mental disorders
Irritability/emotional lability
Severe depression, confusion, psychosis
Diabetes
Frequency < 20%
Impaired glucose tolerance:
Increased hepatic gluconeogenesis
Insulin resistance
Hypertension is common
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Surgical pituitary tumor removal
Irradiation/removal of pituitary adenomas (ACTH producing)
Autopsy case. Unoperated macroadenoma of pituitary
"Autopsy case. Unoperated macroadenoma of pituitary."
1999 KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center.
About 20%-25% of Cushing's patients have an adrenal neoplasm.
Usually unilateral and about 50% of neoplasms are likely malignant.
Adrenal carcinoma diagnosis
Associated with liver and lung metastasis
Resection of hyperplastic adrenals may be employed if source of ACTH is apparent.
In surgical approach not feasible, "medical" adrenalectomy may be required:
"Medical" adrenalectomy:
High-dose ketoconazole (Nizoral) (inhibit steroidogenesis)
Metyrapone
Possible patient management: (surgical intevention)
Before surgery: large doses of cortisol
During and immediately after surgery: large doses of cortisol
Tapered cortisol to normal replacement doses (long-term maintenance)
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"Debbie, 54, had experienced a variety of nagging health problems for several years before she was diagnosed with Cushing's Disease caused by a tumor in the pituitary gland. It was affecting every aspect of her life."
Diagnosis: Dexamethasone suppression testing
Initial Screening
Demonstration of increased cortisol production
Cortisol > , following dexamethasone (Decadron) at midnight
Definitive diagnosis:
Failure of urinary cortisol to fall to less than reference level; plasma cortisol to fall to less than the reference level following standard low-dose dexamethasone (Decadron) suppression testing.
Twice as common in women as in man
Most often presents between 30 in 50 years of age
Adrenal adenoma associated with excessive aldosterone production; however, another contending idea is that an idiopathic bilateral adrenal hyperplasia may be responsible for primary aldosteronism.
Unilateral adenoma (usually small; either side)
Conn's syndrome
Conn's --primary aldosteronism:"Adrenal cortical adenoma There is a solitary, well-demarcated mass with the typical mottled yellow color of adrenal cortex."
1999 KUMC Pathology and the University of Kansas, used with permission; courtesy of Dr. James Fishback, Department of Pathology, University of Kansas Medical Center.For more information concerning endocrine pathology
Hyperplastic adrenal glands -- abnormal secretion
Malignant tumor
Adrenal carcinoma (rare)
Physiological Effects of aldosterone hypersecretion
Increased renal distal tubule or exchange of sodium for secreted potassium and hydrogen ions -- body potassium depletion/hypokalemia
Diagnosis Criteria:
Diastolic hypertension (no edema)
Renin hyposecretion (low plasma renin activity)
Renin secretion does not increase with volume depletion
Aldosterone hypersecretion that is not suppressed with volume expansion
Diastolic hypertension (not very severe)
Secondary to increase sodium reabsorption/volume expansion
Headaches
Polyuria, polydipsia
Impairment of urinary concentrating ability
Weakness
Due to effects of potassium depletion
Tetany
Electrocardiographic changes: consistent with potassium depletion (hypokalemia-- which increases ectopy)
Prominent U waves
Cardiac arrhythmias
Premature contractions
Many effects secondary to potassium loss associated with:
Hypokalemia
May be severe (< 3 mmol/L)
Hypernatremia-- due to:
Sodium retention
Water loss from polyuria
Metabolic alkalosis-- due to
Urinary hydrogen ion loss
Movement of hydrogen ion into potassium-depleted cells
Alkalosis enhanced by potassium deficiency which increases proximal convoluted tubule capacity to reabsorb filtered bicarbonate.
Due to adenoma -- usually treated surgically
May be treated by:
Sodium intake restriction
Aldosterone antagonist (spironolactone (Aldactone))
Prolonged medical management (chronic therapy) may be side effect limited (males)
Gynecomastia
Decreased libido
Impotence
Due to idiopathic bilateral hyperplasia
Symptomatic hypokalemia treated by:
Spironolactone (Aldactone)
Triamterene (Dyrenium)
Amiloride (Midamor)
Surgery if pharmacological treatment fails
Cause: inappropriate increase in aldosterone production due to renin-angiotensin system activation
Accelerated hypertension
Presence of edema disorder
Normal physiologic response to estrogen-induced increased plasma renin substrate and plasma renin activity and to antialdosterone actions of progestogens
In hypertension, cause:
Over production of renin (primary reninism)
Renin over production secondary to reduced renal blood flow/perfusion pressure
Reduced renal artery lumen secondary to atherosclerosis or fiber muscular hyperplasia
Severe arteriolar nephrosclerosis (malignant hypertension)
Profound renal vasoconstriction (accelerated hypertension)
May be caused by rare renin-producing tumors (primary reninism)
Juxtaglomerular cell tumor
Physiological characteristics:
Increased plasma renin activity
Moderate/marked increases in aldosterone levels
Hypokalemic alkalosis
Adrenocorticosteroids and Fetal Lung Maturation
Lung maturation is dependent on fetal cortisol
If delivery is expected before 34 weeks gestation, maternal glucocorticoid supplementation reduces likelihood of respiratory distress syndrome.
Betamethasone (Celestone) preferred due to reduced protein binding -- making more available for placental transfer to the fetal circulation.
Disorder |
Some Examples |
Allergic reactions |
angioneurotic edema, asthma, contact dermatitis, drug reactions, allergic rhinitis, urticaria |
Collagen-vascular pathology |
giant cell arteritis, lupus erythematosus, polymyositis, rheumatoid arthritis, temporal arteritis |
Eye diseases |
allergic conjunctivitis, optic neuritis |
Gastrointestinal |
inflammatory bowel disease than |
Hematologic |
acute allergic purpura, leukemia, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, multiple myeloma |
Infections |
gram-negative septicemia and |
Inflammatory disorders of joints/bones |
arthritis, bursitis,tenosynovitis |
Neurologic |
cerebral edema, multiple sclerosis |
Organ Transplantation |
prevention/treatment of rejection (immunosuppression) |
Pulmonary |
bronchial asthma, prevention of infant respiratory distress,sarcoidosis, aspiration pneumonia |
Renal |
nephrotic syndrome |
Skin |
atopic dermatitis, dermatoses, mycoses fungoides, seborrheic dermatitis |
Thyroid |
malignant exophthalmos, subacute thyroiditis |
adapted from Table 39-2; Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 643. |
Goldfien, A.,Adrenocorticosteroids and Adrenocortical Antagonists, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 635-650.
Williams, G. H and Dluhy, R. G. , Diseases of the Adrenal Cortex, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2035-2056