Lab test and treatment od addison's disease


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  • Lab test and treatment od addison's disease

    1. 1. Lab test and treatment ofAddison's disease Eman abd el raouf ahmad
    2. 2. The content Addison disease investigation Lab test treatment
    3. 3. Note: Addison Disease Also called: Adrenal insufficiency Adrenocortical hypo function, Hypocortisolism
    4. 4. Defect in Addison's disease Auto antigen:21-oH,P450,17OH Tissue cells: enzymes of the adrenal cortex
    5. 5. Investigation: General: K+ ↑ Na+ ↓ glucose ↓ uraemia, mild acidosis, Ca2+ ↑ eosinophilia , neutropenia lymphocytosis and anaemia .
    6. 6. Lab test Blood test.: Measuring your blood levels of sodium, potassium, cortisol and ACTH gives your doctor an initial indication of whether adrenal insufficiency may be causing your signs and symptoms. A blood test can also measure antibodies associated with autoimmune Addison's disease. ACTH stimulation test. This test involves measuring the level of cortisol in your blood before and after an injection of synthetic ACTH. ACTH signals your adrenal glands to produce cortisol. If your adrenal glands are damaged, the ACTH stimulation test shows that your output of cortisol in response to synthetic ACTH is limited or nonexistent.
    7. 7. Corticotrophin-releasing hormone (CRH) stimulation test. This test is used when the ACTH test is abnormal, to help determine the cause of adrenal insufficiency. CRH is a hormone released by the hypothalamusthat stimulates ACTH production by the pituitary gland, which in turn stimulates cortisol production by the adrenal glands. For this test, synthetic CRH is injected intravenously and blood cortisol and ACTH levels are measured at timed intervals after the injection, for example, at 30 and 60 minutes. The normal response is a peak in ACTH levels followed by a peak in cortisol levels. People with Addison disease (underactive or damaged adrenal glands) produce a high level of ACTH but no cortisol. People with secondary adrenal insufficiency have absent or delayed ACTH responses. If someone has a damaged pituitary, CRH will not stimulate ACTH secretion and an absent ACTH response indicates the pituitary is the cause. If ACTH response is delayed, that indicates the hypothalamus is the cause.
    8. 8. Aldosterone. Blood or urine aldosterone levels are measured to help diagnose Addison disease, to determine whether the adrenal gland is producing aldosterone. If the level is low, it is another indication that an individual may have a primary adrenal insufficiency. Electrolytes. Electrolytes (sodium, potassium, chloride and carbon dioxide) are measured to help detect and evaluate the severity of an existing electrolyte imbalance and to monitor the effectiveness of treatment. Electrolytes may be affected by many conditions; with Addison disease, the sodium, chloride, and carbon dioxide levels are often low, while the potassium level may be very high. BUN and Creatinine are tests done to monitor kidney function. Glucose levels may be very low during an adrenal crisis. Glucose may be ordered in order to help monitor the individual during a crisis.
    9. 9. Occasionally Used Tests Insulin-induced hypoglycemia test. Occasionally, a doctor will order this test to learn if pituitary disease (secondary adrenal insufficiency) is the cause of adrenal insufficiency. Glucose and cortisol levels are measured at predetermined intervals after an injection of insulin is used to stress the pituitary gland. In healthy people, blood glucose levels fall and cortisol concentrations increase. In those with adrenal insufficiency, cortisol levels will remain low and glucose levels will fall, then recover slowly.
    10. 10. Renin. Renin activity is elevated in primary adrenal insufficiency because a lack of aldosterone causes increased renal sodium losses. This lowers blood sodium levels and decreases the amount of fluid in the blood (which lowers blood volume and pressure), which in turn stimulates renin production by the kidney. 21-hydroxylase autoantibodies are sometimes ordered as part of the diagnostic process when autoimmune Addison disease is suspected. The test is considered a good indicator of autoimmune Addison disease but is not widely used at this time.
    11. 11. Which antibody tests are positive in Addison’s disease? There are three known potential adrenal proteins targeted by anticortical antibodies (ACAs): 21-hydroxylase (21-OH) 17-hydroxylase (17-OH) Cytochrome P-450 Of these, the most commonly used test is for antibodies to 21-OH, since the other two proteins are also found in non-adrenal tissues, making them less specific and confirmatory for Addison’s. The test will likely be called an adrenal (21-OH) antibody test, or something similar. When positive, there are antibodies in the bloodstream directed against only adrenal cortex tissue, which confirms the presence of autoimmune disease.
    12. 12. Is it possible to test negative for the antibodies and still have Addison’s? Yes. Because Addison’s is not always autoimmune in nature – it can also be caused by infection, trauma, cancer and other etiologies – it is possible to have the disease without the presence of any antibodies. .
    13. 13. Genetic test for HLA Addison’s disease is associated with DRB1*03:01-DQB1*02 (DR17, DQ2) and DRB1*04-DQB1*03:02 (DR4, DQ8). The most strongly associated DRB1*04 allele is DRB1*04:04. The major histocompatibility complex class I related chain – A (MICA) is an additional risk factor. MICA genes are highly polymorphic with over 70 alleles described. Autoantibody testing for anti-21-hydroxylase is more diagnostic in Addison’s disease than genetic testing. Genetic testing does however contribute to a better understanding of the etiology of the disease.
    14. 14. Non lab test X-rays may be used to look for calcification on the adrenal cortex that may be due to a tuberculosis infection. CT (computerized tomography) or MRI (magnetic resonance imaging) scans are sometimes used to look at the size and shape of the adrenal glands and the pituitary. The adrenal glands can be enlarged with infections and cancers. With autoimmune diseases and secondary adrenal insufficiency, the adrenal glands are often normal or small.
    15. 15. treatment 1-hormone replacement is used to correct the insufficient levels of steroids. 2-increase in sodium intake Fludrocortisone Hydrocortisone Prednisone Oral injection Hydrocortisone oral Cortisone oral Dexamethasone oral
    16. 16. treatment All patients with adrenal insufficiency should receive specific hormone replacement. Replacement therapy should correct both glucocorticoid and mineralocorticoid deficiencies. Hydrocortisone ( cortisol ) is the mainstay of treatment. Patients are advised to take glucocorticoids with meals or, if that is impractical, with milk or an antacid, because the drugs may increase gastric acidity and exert direct toxic effects on the gastric mucosa.
    17. 17. TREATMENT: Since the replacement dosage of hydrocortisone does not replace the mineralocorticoid component of the adrenal hormones, mineralocorticoid supplementation is usually needed. This is accomplished by the administration of 0.05 to 0.1 mg fludrocortisone per day by mouth. Patients should also be instructed to maintain an ample intake of sodium (3 to 4 g/d).
    18. 18. TREATMENT: In female patients with adrenal insufficiency, androgen levels are also low. Thus, some physicians believe that daily replacement with 25 to 50 mg of DHEA orally may improve quality of life and skeletal density
    19. 19. Special Therapeutic Problems: During periods of intercurrent illness, especially in the setting of fever, the dose of hydrocortisone should be doubled. With severe illness it should be increased to 75 to 150 mg/d..
    20. 20. Hydrocortisone tablets indication: used to treat endocrine Indication (hormonal) disorders (adrenal insufficiency, Addison's disease).
    21. 21. Pharmacological action Hydrocortisone is the most important human glucocorticoid. It is essential for life and regulates or supports a variety of important cardiovascular, metabolic, immunologic and homeostatic functions. Topical hydrocortisone is used for its anti-inflammatory or immunosuppressive properties to treat inflammation due to corticosteroid-responsive dermatoses. Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger a variety of important cardiovascular, metabolic, immunologic and homeostatic effects.
    22. 22. Mechanism of action: 1. Hydrocortisone binds to the cytosolic glucocorticoid receptor. 2. the receptor the newly formed receptor-ligand complex translocate itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. 3. The DNA bound receptor then interacts with basic transcription factors, causing the increase in expression of specific target genes. The anti-inflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotriene.
    23. 23. Prednisone Prednisone is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. The molecular formula for prednisone is C21H26O5. Chemically, it is 17,21-dihydroxypregna-1, 4-diene-3,11, 20-trione and has the following structural formula:
    24. 24. CLINICAL PHARMACOLOGY Glucocorticoids, such as prednisone, cause profound and varied metabolic effects. In addition, they modify the body’s immune response to diverse stimuli.
    25. 25. fludrocortisone Fludrocortisone (also called 9α-fluorocortisol or 9α-fluorohydrocortisone) is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. . Fludrocortisone has been used in the treatment of cerebral salt wasting.[1] It is used primarily to replace the missing hormone aldosterone in various forms of adrenal insufficiency such as Addison's disease and the classic salt wasting (21-hydroxylase deficiency) form of congenital adrenal hyperplasia. Due to its effects on increasing Na+ levels, and therefore blood volume.
    26. 26. Fludrocortisone is available in 0.1 mg tablets. Typical daily doses for mineralocorticoid replacement are between 0.05 mg - 0.2 mg. Renin plasma, sodium, and potassium is checked through blood tests in order to verify that the correct dosage is reached.
    27. 27. Chemically, fludrocortisone is identical to cortisol except for the substitution of fluorine in place of one hydrogen. Fluorine is a good bioisostere for hydrogen because it is similar in size. The major difference is in its electronegativity.
    28. 28. Dexamethasone Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs that has anti-inflammatory and immunosuppressant effects. It is 25 times more potent than cortisol in its glucocorticoid effect, while having minimal mineralocorticoid effect.
    29. 29. A Classic Case of Addison's Disease A 23-year-old female presented to the Emergency Department complaining of nausea and vomiting for one week. She also reported 8 months of progressively worsening fatigue. The patient was previously very active as a ballet student, but for the past 8 months she stopped participating in ballet because of lack of energy. She was now living with her mother and sleeping or watching television most of the day. One week prior to admission, she developed nausea and had several episodes of vomiting which provoked her visit to the Emergency Department. She also reported a poor appetite for months and had lost 5 to 10 pounds. In addition, she endorsed poor concentration, dry skin and "darkening "of the skin in several areas. She repeatedly denied purposefully restricting food intake or binging and purging behaviors. There was no abdominal pain, diarrhea, fevers, dysuria or headache.
    30. 30. Past medical history was significant for hypothyroidism diagnosed several months prior. The patient was prescribed levothyroxine and subsequently Amour Thyroid but had stopped taking them a month prior because "they made her feel ill." Her only current medication was progesterone to regulate her menstrual cycle. There was no family history of autoimmune or endocrine disorders. Initial examination was remarkable for a blood pressure of 93/50 mmHg and heart rate of 104 beats/min. There were significant orthostatic changes. The patient was a thin, nontoxic appearing Caucasian female in no distress. She was alert, oriented and cooperative. Her examination was otherwise unremarkable except for mild skin hyperpigmentation over the knuckles, elbows and knees. The thyroid, abdominal, and neurological examinations were normal.
    31. 31. Laboratory testing revealed a normal complete blood count. A basic metabolic panel showed a sodium of 111 mmol/L (normal range 135-145), potassium 4.5 mmol/L, chloride 78 mmol/L, bicarbonate 23 mmol/L, glucose 85 mg/dL and creatinine 0.7 mg/dL. Further testing showed serum osmolality at 234 mosm/kg (normal range 275-295), urine osmolality of 162 mosm/kg, and urine sodium less than 20 mmol/L consistent with severe hypovolemic hyponatremia.
    32. 32. A random cortisol level was less than 0.2 μg/dL and a subsequent cortisol level following the administration of 250 mcg of Cosyntropin (Cosynstropin stimulation testing) remained less than 0.2 μg/dL. The plasma adrenocorticotropic hormone (ACTH) level was elevated at 882 pg/dL (normal range 5-27) and adrenal antibody testing (antibodies against the enzyme 21-hydroxylase) was positive with a 1:40 titer (normal<1:10). Further endocrine testing showed an elevated thyroid-stimulating hormone level of 29.2 μIU/mL (normal 0.3-4.7), and a thyroid peroxidase autoantibody level greater than 600 IU/ml (normal<20). Estradiol, folliclestimulating hormone, luteinizing hormone, and prolactin levels were all within normal limits.
    33. 33. references se.html#cat28
    34. 34. thanx