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CMDT 2008
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are found in the serum in about 50% of cases of autoimmune Addison s disease Antibodies to thyroid (45%) and other tissues may be present Elevated plasma renin activity indicates the presence of depleted intravascular volume and the need for higher doses of fludrocortisone replacement
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ciency); cortisol deficiency is also usually present but may not be clinically evident
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Clinical Findings
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A Symptoms and Signs
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The symptoms may include weakness and fatigability, weight loss, myalgias, arthralgias, fever, anorexia, nausea and vomiting, anxiety, and mental irritability Some of these symptoms may be due to high serum levels of IL-6 Pigmentary changes consist of diffuse tanning over nonexposed as well as exposed parts or multiple freckles; hyperpigmentation is especially prominent over the knuckles, elbows, knees, and posterior neck and in palmar creases and nail beds Nipples and areolas tend to darken The skin in pressure areas such as the belt or brassiere lines and the buttocks also darkens New scars are pigmented Some patients have associated vitiligo (10%) Emotional changes are common Hypoglycemia, when present, may worsen the patient s weakness and mental functioning, rarely leading to coma Manifestations of other autoimmune disease (see above) may be present Patients tend to be hypotensive and orthostatic; about 90% have systolic blood pressures under 110 mm Hg; blood pressure over 130 mm Hg is rare Other findings may include a small heart, hyperplasia of lymphoid tissues, and scant axillary and pubic hair (especially in women) Patients with adult-onset adrenoleukodystrophy may present with neuropsychiatric symptoms, sometimes without adrenal insufficiency
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When Addison s disease is not clearly autoimmune, a chest radiograph is obtained to look for tuberculosis, fungal infection, or cancer as possible causes CT scan of the abdomen will show small noncalcified adrenals in autoimmune Addison s disease The adrenals are enlarged in about 85% of cases due to metastatic or granulomatous disease Calcification is noted in about 50% of cases of tuberculous Addison s disease but is also seen with hemorrhage, fungal infection, pheochromocytoma, and melanoma
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Differential Diagnosis
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Addison s disease should be considered in any patient with hypotension or hyperkalemia Unexplained weight loss, weakness, and anorexia may be mistaken for occult cancer Nausea, vomiting, diarrhea, and abdominal pain may be misdiagnosed as intrinsic gastrointestinal disease The hyperpigmentation may be confused with that due to ethnic or racial factors Weight loss may simulate anorexia nervosa The neurologic manifestations of Allgrove s syndrome and adrenoleukodystrophy (especially in women) often mimic multiple sclerosis Hemochromatosis also enters the differential diagnosis of skin hyperpigmentation, but it should be remembered that it may truly be a cause of Addison s disease as well as diabetes mellitus and hypoparathyroidism Serum ferritin is increased in most cases of hemochromatosis and is a useful screening test About 17% of patients with AIDS have symptoms of cortisol resistance AIDS can also cause frank adrenal insufficiency
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B Laboratory Findings
The WBC count usually shows moderate neutropenia, lymphocytosis, and a total eosinophil count over 300/mcL Among patients with chronic Addison s disease, the serum sodium is usually low (90%) while the potassium is elevated (65%) Patients with diarrhea may not be hyperkalemic Fasting blood glucose may be low Hypercalcemia may be present Young men with idiopathic Addison s disease are screened for adrenoleukodystrophy by determining plasma very long-chain fatty acid levels; affected patients have high levels Low plasma cortisol (< 3 mcg/dL) at 8 am is diagnostic, especially if accompanied by simultaneous elevation of the plasma ACTH level (usually > 200 pg/mL) The diagnosis is made by a simplified cosyntropin stimulation test, which is performed as follows: (1) Synthetic ACTH1 24 (cosyntropin), 025 mg, is given parenterally (2) Serum is obtained for cortisol between 30 and 60 minutes after cosyntropin is administered Normally, serum cortisol rises to at least 20 mcg/dL For patients receiving corticosteroid treatment, hydrocortisone must not be given for at least 8 hours before the test Other corticosteroids (eg, prednisone, dexamethasone) do not interfere with specific assays for cortisol Serum DHEA levels are under 1000 ng/mL in 100% of patients with Addison s disease and a serum DHEA above 1000 ng/mL excludes the diagnosis However, serum DHEA levels below 1000 ng/mL are not helpful, since about 15% of the general population have such low DHEA levels, particularly children and elderly individuals Antiadrenal antibodies
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