also called adrenal insufficiency, AI, or hypocortisolism is an endocrine disorder that occurs when the adrenal glands do not produce enough of the hormone cortisol and in some cases, the hormone aldosterone..Addison's DiseaseIt is a disease characterized by progressive anemia, low blood pressure, great weakness, and bronze discoloration of the skin. It is caused by inadequate secretion of hormones by the adrenal cortex.

Addison's disease or Primary adrenal insufficiency was first described by Thomas Addison in 1855OverviewThomas Addison was a renowned 19th-century English physician and scientist. HE is remembered for his "Essay on Disease of the Supra-renal Capsules"

Adrenal GlandsThere two small adrenal glands that lie just above each kidney. Each adrenal gland has an outer part (adrenal cortex) and an inner part (adrenal medulla).Cells in the adrenal glands make various hormones. A hormone passes into the bloodstream and has effects on other parts of the body.

The Adrenal gland, specifically the adrenal cortex, is the gland affected.

Addisons disease develops when the level of adrenal cortex hormone is low due to hyposecretion (lack of secretion).

Cortisol is a hormone that is vital for health. It has many functions which include:Helping to regulate blood pressure.Helping to regulate the immune system.Helping to balance the effect of insulin in regulating the blood sugar level.Helping the body to respond to stress.Aldosterone helps to regulate salts in the blood and helps to control blood pressure.

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.

Clinical Presentation and Laboratory Evaluation of Adrenal Insufficiency

SymptomsFrequency (%)weakness and fatigue100Anorexia100nausea and diarrhea56

SignsFrequency (%)weight loss100hyperpigmentation*97hypotension91vitiligorare

Laboratory FindingsFrequency (%)hyponatremia90hyperkalemia*66hypoglycemia40hypercalcemia6hypereosinophilia * 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 (anti-diuretic hormone, ADH) resulting in impaired free water excretion. In addition, patients with primary adrenal insufficiency lack aldosterone and therefore have urinary sodium loss.

Signs and Symptoms

Addison's can occur in any age group and afflicts both males and females equallyThe disease is characterized by: weight loss muscle weakness fatigue low blood pressure dizziness hypoglycemia

Black freckles may develop over the:foreheadfaceshoulders

bluish-black discoloration may develop around the:nippleslipsmouth,rectumscrotumvagina

Most people with Addison's become:dehydratedhave no appetiteand develop muscle aches, nausea, vomiting, and diarrhea. Many become unable to tolerate cold. Unless the disease is severe, symptoms tend to become more apparent during times of stress.

If Addison's Disease isn't treated severe abdominal pains profound weakness extremely low blood pressure kidney failure and shock may occur, especially if the body is subjected to stress such as an injury, surgery, or severe infection. Death may quickly follow.

The Causes of Addison's DiseaseThe problem may be due to a disorder of the

adrenal glands themselves (primary adrenal insufficiency)

inadequate secretion of ACTH by the pituitary gland (secondary adrenal insufficiency)

primary adrenal insufficiencyMost cases of Addison's Disease are caused by the gradual destruction of the adrenal cortex by the body's own immune systemAs a result of this adrenal cortex damage, often both glucocorticoid (cortisol) and mineralocorticoid (aldostertone) hormones are lacking.Sometimes only the adrenal gland is affected; sometimes other glands also are affected, as in the polyendocrine deficiency syndrome.1. AUTOIMMUNE

2. Tuberculosis (TB)TB is an infection which usually affects the lungs. In some cases the infection can spread to, and gradually destroy, the adrenals.

Less common causes of primary adrenal insufficiency are:3. chronic infection (usually fungal infections)

4. cancer cells spreading from otherparts of the body to the adrenal glands

5. amyloidosis.

Secondary Adrenal Insufficiency(central)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.

1.Long-term glucocorticoid therapyThis 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.

Other causes listed below will be covered in the section on Hypopituitarism.

ChronicAcutePituitary or metastatic tumorPituitary surgeryHistiocytosis XHead traumaHypothalamic tumorsPituitary apoplexyCraniopharyngiomaPostpartum necrosis (Sheehan's)Sarcoidosis Empty sella syndrome Lymphocytic hypophysitis Isolated ACTH deficiency

Cortrosyn Stimulation TestCortrosyn is a synthetic analogue of ACTH and is used as the initial diagnostic test to test the adrenal glands. 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.Diagnostic / Laboratory Test

CRH stimulation test. When the response to the short ACTH test is abnormal, a "long" CRH stimulation test is required to determinethe cause of 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.Overnight Metyrapone Test The overnight metyrapone test is also a test of pituitary reserve which can be done in all patients.

secondary adrenal insufficiency is the cause, doctors may use different imaging tools to reveal the size and shape of the pituitary gland. The most common is the CT scan, which produces a series of x-ray pictures giving a cross-sectional image of a body part. The function of the pituitary and its ability to produce other hormones also are tested.Once a diagnosis of primary adrenal insufficiency has been made, x-ray exams of the abdomen may be taken to see if the adrenals have anysigns of calcium deposits. Calcium deposits may indicate TB.A tuberculin skin test also may be used.

Acute adrenal crisis is an emergency caused by decreased cortisol (more about cortisol below). The crisis may occur in a person with Addison's disease, or as the first sign of adrenal insufficiency. More uncommonly, it may be caused by a pituitary gland disorder. It may also be caused by sudden withdrawal of corticosteroids, removal or injury of the adrenal glands, or destruction of the pituitary gland.

Risk factorsare stress, trauma, surgery, or infection in a person withAddison's disease, or injury or trauma to the adrenal glands or the pituitary gland.

People who have Addison's disease should be taught to recognize signs of potential stress that may precipitate an acute adrenal crisis (cause it to occur suddenly and unexpectedly). Most people withAddison's disease are taught to give themselves an emergency injection ofhydrocortisone in times of stress.Symptoms of an Adrenal Crisis include:

sudden penetrating pain in the lower back, abdomen, or legssevere vomiting and diarrheadehydrationlow blood pressureloss of consciousnessLeft untreated, an Addison's Crisis can be fatal.

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 Addisonian Crisis

TreatmentTreatment of Addison's disease involves replacing, or substituting, the hormones that the adrenal glands are not making. Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. If aldosterone is also deficient, it is replaced with oral doses of a mineralocorticoid called fludrocortisone acetate (Florinef), which is taken once a day. Patients receiving aldosterone replacement therapy are usually advised by a doctor to increase their salt intake. Because patients with secondary adrenal insufficiencynormally maintain aldosterone production, they do not require aldosterone replacement therapy. The doses of each of these medications are adjusted to meet the needs of individual patients.

Treatment (crisis)During anAdrenal Crisis, low blood pressure, low blood glucose, and high levels of potassium can be life threatening. Standard therapy involves intravenous injections of hydrocortisone, saline (salt water), and dextrose (sugar). This treatment usually brings rapid improvement. When the patient can take fluids and medications by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.an intravenous or intramuscular injection of hydrocortisone (an injectable corticosteroid) must be given immediately

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.

Nursing ManagementDx: Fluid Volume Deficit related to inadequate fluid intake and fluid loss secondary to inadequate adrenal hormone secretion.

1. Record weight and changes daily2. Assess skin turgor and mucous membranes3. Instruct patient to report increase thirst4. Monitor lying, sitting, and standing blood pressure frequently 5. Assist patient in selecting and encourage to consume foods and fluids that assist in restoring and maintaining fluid and electrolyte balance6. Provide written and verbal instruction about mineralocorticoids and glucocorticoid therapy

Dx: 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 crisis3. Provide a quiet, nonstressful environment during acute crisis; carry out all activities for the patient

Other Possible Nursing DiagnosisRisk for Imbalanced Nutrition related toDecreased gastrointestinal (GI) enzymes, causing loss of appetite and decreased oral intake toleranceDecreased gastric acid productionNausea, vomiting, diarrheaRisk for Decreased Cardiac Output related toAny situations requiring increased corticosteroids (e.g., stress, infection, GI upsets) may lead to shock or vascular collapseRisk for Deficient Fluid Volume related to: Increase in sodium and water excretion with potassium retentionGI disturbances (e.g., nausea, vomiting, diarrhea, which can be manifestations of Addisons disease).

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 Na5. Administer after meals or with antacids6. Monitor Urine or Blood Glucose Level7. Gradual Withdrawal to prevent Addisonian Crisis- Severe Weaknes, psychologic-letdown

Teaching Patient Self CareHome and Community BasedGive 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.

Thank you

Aldosterone belongs to a class of hormones called mineralocorticoids, also produced by the adrenal glands. It helps maintain blood pressure and water and salt balance in the body by helping the kidney retain sodium and excrete potassium. When aldosterone production falls too low, the kidneys are not able to regulate salt and water balance, causing blood volume and blood pressure to drop.The adrenal glands are part of a very complex endocrine system which produces many hormones that interact with each other. The hypothalamus produces corticotropin-releasing hormone, triggering the pituitary gland to secrete corticotropin, which regulates the production of corticosteroids by the adrenal glands.

The inner part, or the medulla, of the adrenal glands secretes hormones such as adrenaline (epinephrine) that affect blood pressure, heart rate, sweating, and other activities also regulated by the sympathetic nervous system.

The outer part (cortex) secretes many different hormones, including cortisone-like hormones (corticosteroids), androgens (male hormones),and mineralocorticoids, which control blood pressure and the levels of salt and potassium in the bodyCells in the adrenal cortex (the outer part of the adrenals) make the hormones cortisol and aldosterone. The amount of cortisol that is made is controlled by another hormone called adrenocorticotrophic hormone (ACTH). ACTH is made in the pituitary gland (a small gland that lies just under the brain). ACTH passes into the bloodstream, is carried to the adrenal glands, and stimulates the adrenal glands to make cortisol.

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. Addison's disease can mimic a gastrointestinal disorder (with abdominal cramps, persistent nausea and vomiting, or diarrhea).

Patients with adrenal insufficiency develop hypoglycemia after fasting because of decreased gluconeogenesis.

The most specific sign of primary adrenal insufficiency is hyperpigmentation which is most pronounced in areas of skin exposed to increased friction (knuckles, palmar creases, scars, oral mucosa).Hyperpigmentation is due to stimulation of melanocyte-stimulating hormone by high plasma ACTH levels.3,5 Another specific symptom of primary adrenal insufficiency is salt craving.10

Patients are sometimes misdiagnosed as having depression or anorexia nervosa.Unexplained weight loss, malaise, fatigue, and anorexia are common.there are several other reasons that the body fails to produce enough cortisol.Adrenal insufficiency is usually divided into 2 categories.About 70 percent of reported cases of Addison's disease are caused by autoimmune disorders, in which the immune system makes antibodies that attack the body's own tissues or organs and slowly destroy them.

When first described by Addison, tuberculosis was by far the most common etiology of adrenal insufficiency. Today, tuberculosis remains a major cause of adrenal insufficiency in the developing world with adrenal involvement occurring in 5% of patients with active tuberculosis.

3. The adrenal glands may appear calcified on CT. Fungal diseases such as histoplasmosis, coccidiomycosis and blastomycoses areuncommon additional causes. Patients with AIDs and HIV as describedbelow may develop AI5. amyloidosis - occurs when a substance called amyloid builds up in your organs. Amyloid is an abnormal protein that is usually produced in the bone marrow and can be deposited in any tissue or organ.Because the symptoms progress slowly, they are usually ignored until astressful event like an illness or an accident causes them to become worse.This is called an Adrenal CrisisAcute adrenal crisis is an emergency caused by decreased cortisol (more about cortisol below). The crisis may occur in a person withAddison's disease, or as the first sign of adrenal insufficiency. More uncommonly, it may be caused by a pituitary gland disorder. It may alsobe caused by sudden withdrawal of corticosteroids, removal or injury of the adrenal glands, or destruction of the pituitary gland. Risk factorsare stress, trauma, surgery, or infection in a person withAddison's disease, or injury or trauma to the adrenal glands or the pituitary gland.