Addisons disease

In Partial Fulfillment Of the Requirements for Master in Nursing Major in Medical Surgical Nursing

By: Ann Pryam Bagongon

MRS. Vivian Ceballos Adviser

August 14, 2010

The adrenal, or suprarenal, gland is paired with one gland located near the upper portion of each kidney. Each gland is divided into an outer cortex and an inner medulla. The cortex and medulla of the adrenal gland, like the anterior and posterior lobes of the pituitary, develop from different embryonic tissues and secrete different hormones. The adrenal cortex is essential to life, but the medulla may be removed with no life-threatening effects. The hypothalamus of the brain influences both portions of the adrenal gland but by different mechanisms. The adrenal cortex is regulated by negative feedback involving the hypothalamus and adrenocorticotropic hormone; the medulla is regulated by nerve impulses from the hypothalamus. Hormones of the Adrenal Cortex The adrenal cortex consists of three different regions, with each region producing a different group or type of hormones. Chemically, all the cortical hormones are steroid. Mineralocorticoids are secreted by the outermost region of the adrenal cortex. The principal mineralocorticoid is aldosterone, which acts to conserve sodium ions and water in the body. Glucocorticoids are secreted by the middle region of the adrenal cortex. The principal glucocorticoid is cortisol, which increases blood glucose levels.

The third group of steroids secreted by the adrenal cortex is the gonadocorticoids, or sex hormones. These are secreted by the innermost region. Male hormones, androgens, and female hormones, estrogens, are secreted in minimal amounts in both sexes by the adrenal cortex, but their effect is usually masked by the hormones from the testes and ovaries. In females, the masculinization effect of androgen secretion may become evident after menopause, when estrogen levels from the ovaries decrease. Hormones of the Adrenal Medulla The adrenal medulla develops from neural tissue and secretes two hormones, epinephrine and norepinephrine. These two hormones are secreted in response to stimulation by sympathetic nerve, particularly during stressful situations. A lack of hormones from the adrenal medulla produces no significant effects. Hypersecretion, usually from a tumor, causes prolonged or continual sympathetic responses.

Hypothalamus-Pituitary Function to Adrenal Gland

The hypothalamus sends CRH to the pituitary, which responds by sending out ACTH. ACTH then causes the adrenals to release cortisol into the bloodstream.

Addison's disease In 1855, Thomas Addison described patients with "general languor and debility.... and a peculiar change of color in the skin..." The patients died and had diseased adrenal glands. Addison thus realized the adrenal glands are essential for life. In 1950, the Nobel Prize was awarded to Kendall, Reichstein, and Hench for the isolation and synthesis of adrenal cortical hormones and their uses in disease. Addisons disease is another name for primary chronic adrenal insufficiency. It is a condition where the adrenal cortex (the outer layer of the adrenal gland that produces mineralocorticoids, glucocorticoids, and androgens) is progressively destroyed, resulting in decreased secretions of the hormones. Addisons disease occurs in about 4 out of 100,000 Americans each year. Even though it is seen throughout the lifespan in both genders, it most commonly occurs in middle-aged white females. Adrenal insufficiency is usually divided into 2 categories. 1. Primary adrenal insufficiency (Addison's disease): The defect is in the adrenal gland. In primary adrenal insufficiency there is a lack of both cortisol and aldosterone in most cases, but occasionally there may be a deficiency in cortisol alone. 2. Secondary (central) adrenal insufficiency: The defect is in the hypothalamic-pituitary area and is due to ACTH deficiency. Usually, this is associated with other pituitary hormone deficiencies if due to pituitary disease, but there may be isolated ACTH deficiency. Etiology of Adrenal Insufficiency Primary adrenal insufficiency (Addison's disease) [Elevated ACTH & Low Cortisol ] Addison's disease may be caused by adrenal dysgenesis/hypoplasia, adrenal destruction or impaired steroidogenesis. Some of the more common causes are listed below. 1. Autoimmune adrenal insufficiency. Autoimmune Addison's disease may occur by itself or as part of an autoimmune polyendocrine syndrome. In autoimmune polyendocrine syndrome type 1 (APS-1), hypoparathyroidism and mucocutaneous candidiasis usually occur along with adrenal insufficiency. Recently, the cytochrome P450 cholesterol side chain cleavage enzyme (P450-SSC) used in the steroid synthetic pathway was found to be the autoantigen. In APS-2, adrenal insufficiency is associated with type 1 diabetes mellitus and autoimmune thyroiditis. The major

2.

3.

4.

5.

6.

7.

antigen in this syndrome appears to be 21-hydroxylase (P450c21), an enzyme important in the steroid synthetic pathway (see Congenital Adrenal Hyperplasia lecture). Other autoimmune syndromes may also occur including vitiligo, alopecia and pernicious anemia. Autoimmune Addison's disease is more common in women than men and tends to have an onset in young adulthood. Infections: Tuberculosis of the adrenals is the most common cause of adrenal insufficiency worldwide though relatively less common in the United States. The adrenal glands may appear calcified on CT. Fungal diseases such as histoplasmosis, coccidiomycosis and blastomycoses are uncommon additional causes. Patients with AIDs and HIV as described below may develop AI. HIV and the adrenals. Clinical adrenal insufficiency is rare though subtle adrenal dysfunction is common as HIV disease progresses. As with all infiltrative diseases, about 90% of the gland must be destroyed before clinical adrenal insufficiency occurs. Factors involved include o Infections especially CMV but also fungi, mycobacteria and Toxoplasma o Medications including ketoconazole which blocks steroidogenesis and rifampin, phenytoin and opiates which increase steroid metabolism o Cytokines such as interleukin-1 and tumor necrosis factor may suppress the HPA axis. Bilateral adrenal hemorrhage. As with other causes, one should have a high degree of suspicion for this in a patient who is postoperative, on anticoagulants or has a tendency toward thrombosis or coagulopathy. The patient often presents acutely with abdominal, flank or back pain and lifethreatening hypotension. The condition has occurred in patients with antiphospholipid syndrome where a lupus anticoagulant is responsible for thrombosis and/or hemorrhage. Metastatic disease to the adrenal. This may occur with any malignancy metastatic to the adrenal that destroyed at least 90% of both adrenals. However, more often adrenal involvement is present without clinical adrenal insufficiency. Common malignancies with metastatic adrenal involvement. Adrenomyeloneuropathy. This occurs in young men associated with neurologic disease. It is an X-linked peroxisomal disorder characterized by progressive demyelination of the CNS along with adrenal insufficiency. The defect is a deficiency of an enzyme which catabolizes very-long-chain fatty acids to ketones. Familial glucocorticoid deficiency. This is a rare autosomal recessive disorder with adrenal unresponsiveness to ACTH. A mutation in the ACTH receptor has not yet been identified.

Secondary (central) adrenal insufficiency [Low ACTH & Low Cortisol]

1. Long-term glucocorticoid therapy-

This is most common type of secondary AI. It occurs with the use of synthetic glucocorticoids which suppress ACTH secretion as expected; stopping the glucocorticoids may then lead to adrenal insufficiency. 2. Other causes listed below will be covered in the section on Hypopituitarism.

Chronic Acute Pituitary or metastatic tumor Pituitary surgery Histiocytosis X Head trauma Hypothalamic tumors Pituitary apoplexy Craniopharyngioma Postpartum necrosis (Sheehan's) Sarcoidosis Empty sella syndrome Lymphocytic hypophysitis Isolated ACTH deficiency

Clinical Presentation and Laboratory Evaluation of Adrenal Insufficiency Addison's original description of a "general languor and debility, feebleness of the heart's action, irritability of the stomach and a peculiar change in the color of the skin" summarize the main clinical features of the disease. Hydrocortisone, as above, is the principal glucocorticoid produced by the adrenal and is essential in times of stress. Pathophysiology: The central alteration is cardiovascular: reduced cardiac output and decreased vascular tone with relative hypovolemia. As a result, vasopressin is secreted which leads to water retention and hyponatremia. Symptoms weakness and fatigue Anorexia nausea and diarrhea Signs weight loss hyperpigmentation* hypotension vitiligo Frequency (%) 100 100 56 Frequency (%) 100 97 91 rare

Laboratory Findings Frequency (%) hyponatremia 90 hyperkalemia* 66 hypoglycemia 40 hypercalcemia 6 hypereosinophilia * Primary Adrenal Insufficiency only *Hyperpigmentation only occurs in primary adrenal insufficiency due to the increased secretion of lipotropin which contains melanocyte stimulating MSH and is a component of the ACTH precursor peptide (POMC). *Hyperkalemia, which is due to a lack of aldosterone, is only present in primary adrenal insufficiency. In secondary insufficiency, only cortisol production is affected while aldosterone production remains intact since it is regulated primarily by the renin-angiotensin system. Therefore, features associated with aldosterone deficiency such as hyperkalemia or profound volume depletion are absent in secondary deficiency.

Hyponatremia is present in both primary and secondary disease. The hyponatremia occurs in both types due to an increase in vasopressin (antidiuretic hormone, ADH) resulting in impaired free water excretion. In addition, patients with primary adrenal insufficiency lack aldosterone and therefore have urinary sodium loss. Autoimmune Addison's disease develops over several years. Autoantibodies appear first to the antigens described above. As functional adrenal mass starts to decline, plasma renin activity increases at rest followed by a low plasma aldosterone. Zona fasciculata dysfunction then becomes evident (months to years later) by an elevation in the afternoon ACTH level. This is followed by a depressed cortisol response to ACTH stimulation (see Cortrosyn stimulation test below) and finally by decreased basal cortisol levels and the appearance of clinical symptoms. Test Results That Suggest Addison's Disease Test Blood Chemistry Serum Na Serum K Ratio of Serum Na:K Plasma Glucose, fasting Plasma HCO3 BUN Hematology Hct WBC Count Lymphocytes Eosinophils Imaging Elevated Low Relative lymphocytes Increased < 135 mEq/L > 5 mEq/L <30:1 < 50 mg/dL < 15-20 mEq/L > 20 mg/dL Result

Evidence of calcification in adrenal areas Renal TB Pulmonary TB [Chart courtesy of Merck.com. Available at http://merck.com/mmpe/sec12/ch153/ch153b.html] Tests for Diagnosis of Adrenal Insufficiency Cortrosyn Stimulation Test Cortrosyn is a synthetic analogue of ACTH and is used as the initial diagnostic test to test the adrenal glands. 250 mcg of IV or IM Cortrosyn is given and cortisol levels are drawn at time 0, 30 and 60 minutes. Normal response is a stimulated cortisol level above 18-20 mcg/dl . In primary adrenal insufficiency, the cortisol level starts out low and does not rise or rises minimally. In secondary adrenal insufficiency, the cortisol level starts out low and rise but does not get above 18 mcg/dl. Lack of an aldosterone response is also consistent with primary adrenal insufficiency. An abnormal test requires either adrenal destruction or chronic pituitary insufficiency (lack of ACTH results in adrenal atrophy). If acute pituitary insufficiency should occur, this test may still be "normal" because the adrenals have not yet atrophied and can respond to the cortrosyn stimulation. In this clinical situation either a insulin tolerance or a metyrapone test (described below) is recommended to test the pituitary function. A low dose (1 mcg) ACTH test has been studied, however it is not accepted uniformly by endocrinologists and is not currently commercially available. ACTH Level In the setting of a low cortisol level, a high ACTH level suggests primary adrenal insufficiency while a normal (inappropriately normal) or low level is consistent with secondary adrenal insufficiency. Insulin Tolerance Test The insulin tolerance test is the "gold standard" used to test the hypothalamic and pituitary response to a hypoglycemic stress and thus indirectly tests the adrenal. IV insulin is given at 0.1-0.15 U/kg with the aim of achieving a plasma glucose level of less than 40 mg/dl. With this stimulus, a normal response would be a rise in ACTH (as well as growth hormone) which would then stimulate cortisol to greater than 18 mcg/dl. If

pituitary reserve is impaired, a suboptimal response will be seen. This test should not be done in patients with a seizure disorder, known coronary artery disease and older patients. The test is not necessary if the cortrosyn stimulation test is abnormal. It is primarily used to test pituitary reserve which may be abnormal even when the Cortrosyn test is normal (as described above). Overnight Metyrapone Test The overnight metyrapone test is also a test of pituitary reserve which can be done in all patients. Metyrapone is a compound which blocks the last step in cortisol synthesis from 11-deoxycortisol (compound S) to cortisol. It is given at 11 pm and blood is drawn the following morning at 8 am for cortisol, ACTH and 11-deoxycortisol. In a normal individual, cortisol production is diminished by the Metyrapone resulting instimulation of ACTH secretion. ACTH, in turn, stimulates the adrenals to increase synthesis of the precursors of cortisol, including the hormone of interest, 11-deoxycortisol (normal values after Metarypone testing: cortisol< 5 mcg/dl, ACTH >100 pg/ml, 11-deoxycortisol > 7 mcg/dl). In someone with an impaired pituitary, the cortisol level would be low (assuming enough metyrapone was given) but ACTH and 11-deoxycortisol will not rise to the expected levels. As above, the test is not necessary if the cortrosyn stimulation test is abnormal. This test requires an inpatient stay because of the risk of precipitating an adrenal crisis and is therefore not routinely performed. Addisonian Crisis Signs and symptoms to watch out: Cyanosis, fever, and classic signs of Shock: Pallor, apprehension, rapid and weak pulse, rapid respirations and low blood pressure Slight overexertion, exposure to cold, and acute infections, decrease salt intake may lead to circulatory collapse, shock and death Deacrease blood glucose and Na but increase K and leukocytosis Medical Management Restore blood circulation, administer IV fluids, monitor V/S and place patient in recumbent position with legs elevated. Administer intravenous Hydrocortisone, followed by 5% dextrose in normal saline. Vasopressor amines may be required if hypotension persist. Antibiotics may be prescribe for infection Oral intake may be initiated as soon as tolerated.

 If Adrenal gland does not regain function, lifelong replacement of corticosteroids and mineralocorticoids is required. Implementation for Patients taking: Cortisone/Florinef 1. Monitor V/S, I and O, Wt. 2. Encourage Bed rest 3. Avoid Exposure to Infection 4. Diet: High CHON, CHO, K, low Na 5. Administer after meals or with antacids 6. Monitor Urine or Blood Glucose Level 7. Gradual Withdrawal to prevent Addisonian Crisis- Severe Weaknes, psychologic-letdown Nursing Management Fluid Volume Deficit related to inadequate fluid intake and fluid loss secondary to inadequate adrenal hormone secretion. 1. 2. 3. 4. 5. Record weight and changes daily Assess skin turgor and mucous membranes Instruct patient to report increase thirst Monitor lying, sitting, and standing blood pressure frequently Assist patient in selecting and encourage to consume foods and fluids that assist in restoring and maintaining fluid and electrolyte balance 6. Provide written and verbal instruction about mineralocorticoids and glucocorticoid therapy Activity intolerance related to generalize weakness secondary to underlying disease process 1. Avoid unnecessary activities and stress that might precipitate hypotensive episodes. 2. Detect signs of infection or presence of stressors that may trigger the crisis 3. Provide a quiet, nonstressful environment during acute crisis; carry out all activities for the patient

Teaching Patient Self Care Home and Community Based Give patient and family explicit verbal and written instructions about the rationale for replacement therapy and proper dosage. Teach how to modify drug dosage and increase salt in times of illness, very hot weather and stressful situation. Instruct patient to modify diet and fluid intake to maintain fluid and electrolyte balance. Advise patient to inform health care providers of steroid use. Urge to wear a medical alert bracelet. Teach patient and family signs of excessive and insufficient hormone replacements.

Journal Reading: Bilateral adrenal histoplasmosis in immunocompetent patients. Rana C, Krishnani N, Kumari N. Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India. Histoplasmosis is a fungal infection caused by Histoplasma capsulatum, which commonly presents as transient pulmonary infection that usually subsides without treatment. Disseminated histoplasmosis may affect almost all systems, including the reticuloendothelial system, lungs, gastrointestinal tract, renal tract, central nervous system, bone marrow, and adrenal glands. Adrenal gland is frequently involved in disseminated histoplamosis but commonly present as unilateral mass; bilateral involvement is rare. It is also rare in immunocompetent hosts and only few cases have been reported in past. We report four cases of adrenal histoplasmosis with bilateral involvement. These cases were initially diagnosed cytopathologically on fine needle aspirations performed on adrenal glands. All these patients were immunocompetent and two of them also had associated adrenal insufficiency. Diagnosis of adrenal histoplasmosis can be easily made on fine needle aspiration cytology. Adrenal histoplasmosis can occur in immunocompetent individuals and should be considered in differential diagnosis of bilateral adrenal masses in immunocompetent individuals. Diagn. Cytopathol. 2010. (c) 2010 Wiley-Liss, Inc. http://addisonsdisease.researchtoday.net/archive/6/7/785.htm

Bibliography

Bornstein SR, moderator. Adrenocortical tumors: recent advances in basic concepts and clinical management. Ann Intern Med 130: 759771, 1999. Smeltzer, Suzzane C. and Bare, Brenda G. Textbook of MedicalSurgical Nursing. 9th ed. Philadelphia: Lippincott Williams and Wilkins. 2000. Doenges, M. E., Moorehouse, M. F. and Geissler, A. C. Nursing Care Plans: Guidelines for Planning and Documenting Patient Care. 3rd ed. Philadelphia: F. A. Davis Co. 1993. Udan, J. Q. Medical-Surgical Nursing: Concepts and Clinical Application. 1st ed. Philippines: Educational Publishing House. 2002. http://www.wikidoc.org/index.php/Addison%27s_disease http://addisonsdisease.researchtoday.net/archive/6/7/785.htm http://my.clevelandclinic.org/disorders/Addisons_Disease/hic_Addis ons_Disease.aspx http://merck.com/mmpe/sec12/ch153/ch153b.html