Guidelines for Ordering a Urinalysis

1. Outpatient Screening/Case-Finding

   i. A urinalysis is not indicated in asymptomatic individuals whose history and physical examination findings are within the normal ranges for age and sex.

   ii. In specific subsets of the population with higher prevalence of renal disease, urinary tract infections, liver disease, and diabetes mellitus, the urinalysis may be useful to identify those who are significantly at risk, including but not limited to the following:

   • Pregnancy
   • Elderly (> 60 years) men and women
   • Obese individuals with a positive family history of diabetes mellitus
   • Individuals taking hepato- or nephrotoxic drugs
   • Individuals routinely exposed to toxic chemicals in the work or home environment

2. Diagnosis

   i. The urinalysis is indicated in patients where there are clinical findings suggestive of urinary tract infections, renal disease, diabetes mellitus, and liver disease. The urinalysis should include physical, chemical, and microscopic evaluation.

   ii. The urinalysis may be useful in patients with previous positive findings for proteinuria, microhematuria, bacteriuria, pyuria, or diabetes mellitus.

3. Monitoring

   i. Repeat urinalysis is not indicated in patients in whom no abnormality is suspected.

   ii. Repeat urinalysis may be useful in the following:

   • Documenting evidence of response to treatment for urinary tract infections, renal disease, and diabetes mellitus
   • Patients in whom there is concern that treatment has not been effective
   • Patients taking medications which are hepato- or nephrotoxic
   • Individuals routinely exposed to toxic chemicals
   • Pregnancy

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. CBCs are not indicated in asymptomatic individuals whose history and physical examination findings are within reference for age and sex.’

   • Routine use of CBCs in populations of low disease prevalence have a low diagnostic yield

   ii. In specific subsets of the population with higher prevalence of anemia, the CBC may be useful to identify those who are significantly anemic because of poor nutrition or undiagnosed chronic illness, including but not limited to the following:

   • Pregnant women in whom there is a suspicion that iron supplementation or nutrition has not been adequate
   • The elderly (>75 years old)
   • Recent immigrants from Third World countries, especially persons at increased risk of malnourishment
   • Individuals on diets which are nutritionally unbalanced

2. Diagnosis of Suspected Abnormality

   i. The CBC is useful in the diagnosis of infection or primary hematological disorders.

   • The CBC is indicated in patients in whom there are clinical findings suggestive of anemia, including fatigue, mucous-membrane pallor, sore tongue, peripheral neuropathy, abnormal bleeding, or findings suggestive of polycythemia

   ii. The CBC may be useful in conditions that may be associated with anemia and/or abnormal leukocyte counts, such as rheumatoid arthritis, malignancy (e.g., lymphoma)and renal insufficiency.

   iii. The CBC may be useful when fever is present or when infection is suspected, especially when other confirmatory findings are absent.

3. Monitoring

   i. Repeat CBCs are not indicated in patients in whom no abnormality is suspected.

   ii. Repeat CBCs may be useful in the following:

   • Patients in whom there is concern that treatment has not been effective
   • Documenting evidence of response to treatment for anemia
   • Patients with infection not improving clinically under collaborative care
   • Patients with leukopenia (leukocyte count is less than 4,500/j.d)
   • Patients taking cytotoxic medications

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The ESR is not indicated in asymptomatic persons.

   ii. An ESR should be ordered/performed selectively and interpreted with caution in patients whose symptoms are not adequately explained by a careful history and physical examination.

   • Significant infections or inflammatory or neoplastic disease are unlikely in such patients, and the ESR must be markedly elevated to be diagnostically useful.

   • Extreme elevation of the ESR seldom occurs in patients with no evidence of serious disease.

2. Diagnosis

   i. The ESR is useful for the diagnosis of temporal arteritis (giant cell arteritis) and polymyalgia rheumatica.

   • A normal ESR virtually excludes the diagnosis of temporal arteritis in most patients who are suspected of having the disease.

   • When there is strong clinical evidence for temporal arteritis and the ESR is normal, further efforts to diagnose temporal arteritis are required.

   ii. A careful history and physical examination are the most reliable means of making a diagnosis of rheumatoid arthritis. In patients with an equivocal examination, an ESR may be indicated and an abnormal result is a clue to the presence of this disease.

   iii. The ESR may be indicated in the differential diagnosis of solitary bone lesions.

   iv. The ESR may be indicated in the diagnosis of metastatic breast cancer.

   v. The ESR may be indicated as a means of excluding suspected vertebral osteomyelitis.

   vi. The ESR may assist in the differential diagnosis of certain infectious, inflammatory, and malignant disorders.

   vii. The ESR may provide assistance in distinguishing spinal pain of organic origin from mechanical origin.

3. Monitoring

   i. The ESR is useful for monitoring temporal arteritis and polymyalgia rheumatica.

   ii. The judicious use of the ESR combined with other clinical and laboratory observations may be of value in patients with rheumatoid arthritis and systemic lupus erythematosus.

   iii. The ESR may be indicated for monitoring patients with Hodgkin’s disease.

   iv. The ESR may be indicated for monitoring patients with acute rheumatic fever.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. Biochemical profiles are not routinely indicated for screening asymptomatic patients.

   ii. Selected components of biochemical profiles may be indicated for screening and/or case-finding in adults: serum glucose, cholesterol and creatinine.

   iii. Specific components of biochemical profiles that are not indicated for screening include the following: serum calcium, alkaline phosphatase, uric acid, sodium, potassium, chloride, AST, lactic dehydrogenase (LDH), total protein, albumin, and total bilirubin.

   iv. In cases where current technology and/or cost prohibit selective test ordering, biochemical profiles should be used with caution because of a greater likelihood of false-positive findings in low disease-prevalent populations.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. A serum or plasma glucose test is not routinely indicated to screen for diabetes mellitus in asymptomatic, nonpregnant adults.

   ii. A serum or plasma glucose test may be indicated in individuals who are at increased risk for diabetes mellitus.

   • Risk factors for diabetes mellitus include age (>50 years), family history in a first degree relative, personal history of gestational diabetes, body weight that exceeds generally accepted standards by at least 25 percent, or membership in an ethnic group that has a high prevalence of diabetes.

   iii. A serum or plasma glucose test is recommended for all pregnant women to screen for gestational diabetes.

   • A serum or plasma glucose test obtained after a 50-gram glucose load is the preferred screening procedure.

2. Diagnosis

   i. A fasting or random plasma glucose measurement is useful for the diagnosis of diabetes mellitus in persons who present with symptoms of hyperglycemia (rapid weight loss, polyuria, polydipsia) and/or diabetes (for example, peripheral neuropathy or peripheral vascular disease).

   • An oral glucose tolerance test may be indicated to confirm equivocal tests.

   ii. In patients with clinical findings of hypoglycemia, a serum or plasma glucose should be ordered.

   • The true hypoglycemia syndrome refers to the presence of adrenergic (sweating, tremor, tachycardia, anxiety, and hunger) or neuroglycopenic (dizziness, headache, clouded vision, blunted mental acuity, confusion, abnormal behavior, coma) signs and symptoms in the presence of a low serum or plasma glucose concentration.

3. Monitoring

   i. A plasma or serum glucose test is not optimal as the primary modality for monitoring glycemia in insulin-dependent (Type I) diabetic patients with diabetes.

   • Daily self-monitored blood glucose measurement, along with periodic (3-4 times per year) measurement of glycated hemoglobin (glycosylated hemoglobin) are appropriate monitoring evaluations

   ii. In non-insulin dependent (Type II) diabetes, laboratory performed plasma or serum glucose testing may be indicated every three months.

   • Self-monitored blood glucose measurement may be indicated one or two times per day to assess glycemia

   • Glycated hemoglobin measurements are indicated at least two times per year to provide an index of mean glucose levels as a measure of overall chronic glucose control

   iii. Laboratory performed fasting and postprandial plasma glucose measurements are indicated in diet-treated gestational diabetes every one to two weeks from time of diagnosis until 30 weeks’ gestation, and once or twice weekly thereafter.

1. Outpatient Screening/Case-Finding

   i. Serum urea nitrogen and creatinine tests are not indicated in asymptomatic individuals whose history and physical examination findings are within reference ranges.

   ii. Individuals who have a higher likelihood of developing renal dysfunction may benefit from measuring serum urea nitrogen and creatinine concentrations

   • Patients with hypertension, diabetes mellitus, congestive heart failure, cirrhosis, prostatic hypertrophy, exposure to nephrotoxic agents, taking diuretics, eating a high-protein diet, and over 75 years of age, are candidates for these tests.

2. Diagnosis

   i. Serum urea nitrogen and creatinine tests are useful in the diagnosis of renal disorders.

   • These tests are indicated in patients with clinical findings suggestive of renal dysfunction, such as pallor, anemia, anorexia, unexplained weight loss, polyuria, urinary hesitancy, nocturia, renal colic, dehydration, retinopathy, hypertension, skin lesions of vasculitis, and/or an abnormal urinalysis (high specific gravity, proteinuria, hematuria, pyuria, presence of crystals and/or casts).

   ii. Measuring serum urea nitrogen and creatinine concentration, or creatinine alone, may be useful in hypertension or diabetes patients.

   iii. Conditions in which both the serum urea nitrogen and creatinine concentration may be indicated include but are not limited to the following:

   • Gastrointestinal bleeding, complicated by some degree of renal insufficiency
   • A suspected diagnosis of water intoxication
   • Syndrome of inappropriate antidiuretic hormone secretion

3. Monitoring

   i. Measuring serum urea nitrogen and serum creatinine concentration, or creatinine alone, may be useful for the following conditions and at the following frequencies:

   • Uncomplicated hypertensive patients, every one to two years
   • Chronic renal disease, every four to six months
   • Patients in acute renal failure, every one to two days

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum calcium test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum calcium as a screening test for occult metabolic bone disease or malignancy will result in a low diagnostic yield.

   • For most of these conditions, the post-test probability of disease after abnormal calcium results is not sufficiently high to warrant the inclusion of calcium determinations in a screening profile.

2. Diagnosis

   i. The serum calcium test is useful in the evaluation of patients who present with clinical evidence of hypercalcemia (anorexia, nausea, constipation, polyuria, polydipsia, bone pain, and mental or neurologic aberrations) or hypocalcemia (paresthesias, muscle cramps, tetany, weakness, convulsions).

   ii. The serum calcium test may be useful in the evaluation of patients with hypertension, renal calculi, peptic ulcer disease, metabolic bone disease, malignant disorders, history of previous neck surgery, alcoholism, and acid-base imbalance.

3. Monitoring

   i. Repeat serum calcium measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Serum calcium may be used to follow the course of hypercalcemia and hypocalcemic disorders and their response to care.

   • A serum calcium level should be interpreted with knowledge of the serum albumin level

   Rating:	Established
   Evidence:	Class II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum inorganic phosphorus test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum inorganic phosphorus as a screening test for various malignant, inflammatory, bony, renal and metabolic disorders will result in a low diagnostic yield.

   • For most of these conditions, the post-test probability of disease after abnormal inorganic phosphorus results is not sufficiently high to warrant the inclusion of inorganic phosphorus determinations in a screening profile.

2. Diagnosis

   i. The serum inorganic phosphorus test is useful in the evaluation of patients suspected of having metabolic bone disease, renal disorders, endocrime disorders, and acid-base imbalance.

3. Monitoring

   i. Repeat serum inorganic phosphorus measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Serum inorganic phosphorus may be used to follow the course of hyperphosphatemic and hypophosphatemic disorders and their response to care.

   • A serum inorganic phosphorus level should be interpreted with knowledge of the serum urea nitrogen level.

   Rating:	Established
   Evidence:	Class II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum total protein and albumin tests are not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum total protein and albumin as screening tests for malnutrition, protein loss or breakdown, and impaired protein synthesis will result in a low diagnostic yield.

2. Diagnosis

   i. The serum total protein and albumin tests may be useful in the evaluation of patients with suspected malnutrition, liver disorders, renal disease, malabsorption, recurrent infections, blood dyscrasias, and malignancies such as multiple myeloma.

   ii. Results which fall outside the reference range for these tests may require a protein electrophoresis determination and/or immunoelectrophoresis.

3. Monitoring

   i. Repeat serum total protein and albumin measurements are not indicated in patients in whom no abnormality is suspected.

   ii. Serum total protein and albumin determinations have limited value in monitoring disorders associated with changes in serum protein levels.

   Rating:	Established
   Evidence:	Class II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. A total serum cholesterol measurement is recommended at least once in early adulthood and at intervals of five or more years up to age 70.

   • The LDL and HDL cholesterol and serum triglyceride levels should be measured in persons with an elevated total serum cholesterol.

   ii. In patients who demonstrate risk factors for coronary artery disese, a serum total cholesterol is indicated to assess cardiac risk.

   • Risk factors for coronary artery disease include: being male or postmenopausal female, positive family history, smoker, hypertension, history of hyper-cholesterolemia, low HDL-cholesterol levels, diabetes mellitus, previous stroke, peripheral vascular disease, or severe obesity.

2. Diagnosis

   i. The total serum cholesterol is useful in the diagnosis of patients with coronary artery disease and peripheral vascular disease.

   ii. The total serum cholesterol may be useful in the diagnosis of nephrotic syndrome, pancreatitis, and liver disease.

3. Monitoring

   i. Total serum cholesterol may be used to follow up hypercholesterolemic related disorders and their response to care.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum alkaline phosphatase test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum alkaline phosphatase as a screening test for unsuspected skeletal and hepatobiliary diseases provides a low diagnostic yield.

   • The pretest probability is low in the general population for those disorders most strongly associated with an elevated alkaline phosphatase.

   • The serum alkaline phosphatase test is not specific for any particular disorder or sensitive enough to identify most patients with any single disease.

2. Diagnosis

   i. The serum alkaline phosphatase may be useful in the evaluation of patients who present with clinical evidence of a skeletal disorder with increased osteoblastic activity, and are suspected of having either Paget’s disease of bone (osteitis deformans), osteomalacia, primary bone tumors, metastatic bone tumors or primary hyperparathyroidism.

   • Clinical evidence may include backache, bone pain, bone swelling, abnormal plain film bone radiographs, and bone scans.

   ii. The serum alkaline phosphatase test may be useful in the evaluation of patients who present with clinical evidence of a hepatobiliary disorder such as cholelithiasis with obstruction, drug-induced cholestasis, metastatic tumor or space-occupying lesion in the liver, cirrhosis, hepatitis, and alcoholism.

   • Clinical evidence may include fever, nausea, vomiting, abdominal pain, jaundice, certain medication use, and abnormal liver function tests.

   iii. The serum alkaline phosphatase test may exhibit abnormal results in a number of other disorders.

   • These conditions include intestinal disorders, malignancy, malnutrition, congestive heart failure, renal disorders, thyroid dysfunction, diabetes mellitus, and physiological influences (age, pregnancy, non-fasting patient).

3. Monitoring

   i. Repeat serum alkaline phosphatase measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Periodic determinations of serum alkaline phosphatase may be used to follow the course of a disorder and its response to care.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum prostatic acid phosphatase test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum prostatic acid phosphatase as a screening test for unsuspected cancer of the prostate provides a low diagnostic yield.

   • Assays for serum prostatic acid phosphatase are not sufficiently sensitive to detect prostatic carcinoma in 70 to 80 percent of patients with localized disease (Stage A or B) or S to 15 percent of patients with metastatic prostatic disease.

   • Specificity is low because nearly every method devised for detecting prostatic acid phosphatase exhibits cross-reactivity with other acid phosphatase isoenzymes found widely in human tissues.

2. Diagnosis

   i. The serum prostatic acid phosphatase test may be useful in the evaluation of patients with clinical evidence of prostatic carcinoma.

   • Patients may present with obstructive symptoms (hesitancy, diminished urine stream, dribbling, intermittency), lumbar and/or sacral pain, and have induration or nodular irregularities of the prostate discovered by digital rectal examination.

3. Monitoring

   i. Repeat serum prostatic acid phosphatase measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Serum prostatic acid phosphatase measurement may be used to monitor cancer patients for recurrence after prostatectomy or other ablative care.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum prostate-specific antigen (PSA) test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum PSA as a screening test for unsuspected cancer of the prostate provides a low diagnostic yield.

   • Serum PSA measurements are not sufficiently sensitive to be used alone as a screening test.

   • The specificity of PSA is limited, due to elevations of the antigen occurring in men with benign prostatic hyperplasia or prostatitis.

2. Diagnosis

   i. The serum prostate-specific antien is a useful test in the evaluation of patients with clinical evidence of prostatic carcinoma.

   • Serum PSA measurement is a useful addition to rectal examination and ultrasonography in the detection of prostate cancer.

   • PSA is more sensitive but less specific than prostatic acid phosphatase for prostatic cancer.

3. Monitoring

   i. Repeat serum prostate-specific antigen measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Serum PSA measurements may be useful to detect recurrences of prostate cancer.

   iii. Serum PSA measurements may be useful in monitoring the response to care for prostate cancer.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

NOTE: This test was formerly known as glutamic-oxaloacetic transaminase (SGOT).

1. Outpatient Screening/Case-Finding

   i. The serum AST is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum AST as a sreening test for liver disorders, cardiac disease, and skeletal muscle disorders will result in a low diagnostic yield.

2. Diagnosis

   i. The serum AST test may be useful in the evaluation of patients with suspected liver disorders.

3. Monitoring

   i. Repeat serum AST measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Serum AST may be used to follow the course of various liver disorders and their response to care.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

NOTE: This test was formerly known as Creatine Phosphokinase (CPK).

1. Outpatient Screening/Case-Finding

   i. The serum creatine kinase (CK) test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of the serum creatine kinase (CK) as a screening test for cardiac, skeletal muscle, and central nervous system disorders will result in a low diagnostic yield.

2. Diagnosis

   i. The serum creatine kinase (CK) test is useful in the evaluation of patients who present with clinical evidence of acute myocardial infarction.

   • Fractionation and measurement of CK isoenzymes (CK-MB primarily) augments total CK results.

   ii. The serum creatine kinase (CK) test may be useful in the differential diagnosis of chest pain, hypothyroidism and in the detection of skeletal muscle disorders that are not of neurogenic origin, such as Duchenne Muscular Dystrophy.

3. Monitoring

   i. Measurement of serial levels of serum CK and CK-MB isoenzymes are used to monitor care in acute myocardial infarction.

   ii. Total serum CK may be used to follow patients with certain primary myopathies.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. Routine testing for thyroid disorders is not indicated in asymptomatic individuals.

   ii. Case-finding is indicated in women over 50 years of age who have general symptoms that could be associated with thyroid dysfunction.

2. Diagnosis

   i. The sensitive thyrotropin assay (sTSH) is useful in the evaluation of patients of either sex who present with clinical evidence of thyroid dysfunction.

   • If sTSH is not available, the Free T3, Free T4, or Free T4 Index can be used in the evaluation of suspected hyperthyroidism.

   • For the diagnosis of hypothyroidism, the Free T4 or Free T4 Index, followed by a serum thyrotropin (TSH) test, is acceptable. For patients suspected of having thyroiditis, antithyroid antibody studies may be useful.

3. Monitoring

   i. The sTSH test is indicated for monitoring patient response to care.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum uric acid test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. The use of serum uric acid as a screening test for gout will provide a low diagnostic yield.

   • On the basis of established prevalences, if asymptomatic individuals were screened, those with an elevated uric acid have only a 5 percent chance of having gout

   iii. For case finding, with a pretest probability of 10 percent (prevalence of gout in the U.S. is estimated at 0.3%), the probability that a correct diagnosis will be derived from a positive test is less than 50%.

2. Diagnosis

   i. The serum uric acid test is useful in the evaluation of patients who present with clinical evidence of monoarticular arthritis and are suspected of having gout.

   • Gout is a disorder of purine metabolism where the presence of an elevated serum uric acid level is but one of several criteria necessary for diagnosis.

   ii. The serum uric acid test may be elevated in a number of disorders other than gout which affect urate production or excretion, or both.

   • These conditions include: (1) increased nucleic acid turnover related to hematological disorders, malignancy and psoriasis; (2) reduced excretion due to renal dysfunction, certain drugs, and organic acidosis, and (3) miscellaneous causes such as arteriosclerosis and hypertension.

   iii. Serum uric acid measurement is not useful as a test for renal function because the reference range is wide and the rise in uric acid in renal dysfunction is not constant.

3. Monitoring

   i. Repeat serum uric acid measurement is not indicated in patients in whom no abnormality is suspected.

   ii. Periodic determinations of serum uric acid may be useful in monitoring patients under care for gout.

   iii. Serial serum uric acid analyses are sometimes of value in estimating prognosis in toxemia of pregnancy.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The rheumatoid factor test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference ranges for age and sex.

   ii. The use of rheumatoid factor as a screening test for rheumatoid arthritis will result in a low diagnostic yield.

   • If the rheumatoid factor test is ordered when there is little likelihood of rheumatoid arthritis (e.g., low-back pain) and where the pretest probability is low (1 percent). the predictive value will be very low.

   iii. For case finding, with a pretest probability of 10 percent (prevalence of rheumatoid arthritis in the U.S. is estimated at 0.5% to 3%), the probability that a correct diagnosis will be derived from a positive test is less than 50%.

   iv. Many more false-positive results as compared to true-positive results will occur from screening.

   • There is less than a one in five chance in a screening program that an individual with a positive rheumatoid factor test will have rheumatoid arthritis.

2. Diagnosis of Rheumatoid Arthritis and Related Disorders

   i. The rheumatoid factor test is useful in the evaluation of patients who present with clinical evidence of symmetric polyarthritis and are suspected of having rheumatoid arthritis.

   ii. Seronegative patients suspected of having rheumatoid arthritis should be retested in six months.

   iii. The usefulness of the rheumatoid factor test among patients already known to have rheumatoid arthritis is primarily prognostic. Patients with high titers of rheumatoid factor tend to have more severe disease, subcutaneous nodules, vasculitis, and poorer long-term prognosis. However, individual patients will vary with these manifestations.

   • Rheumatoid factor is positive in a significant subset of patients with other rheumatic and nonrheumatic diseases, but its presence or absence weighs little in the diagnosis of the majority of such diseases.

   • The disappearance of the rheumatoid factor in a patient with Sjogren’s syndrome may herald the onset of lymphoma.

   • The rheumatoid factor is frequently positive in cryoglobulinemia.

3. Monitoring

   i. Repeat rheumatoid factor tests are not indicated in patients in whom rheumatoid arthritis is not suspected.

   ii. The use of the rheumatoid factor test to guide treatment in patients with rheumatoid arthritis is not recommended. There is little evidence to suggest that an individual rheumatoid arthritis patient with a highly positive rheumatoid factor test will fare better if treated earlier or more aggressively.

   iii. The rheumatoid factor test is not a generally accepted measure of improvement in rheumatoid arthritis.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The ANA test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference ranges for age and sex.

   ii. The use of the ANA as a screening test for systemic lupus erythematosus, drug-induced lupus, or mixed connective tissue disease where a moderate pretest probability is low will result in a low diagnostic yield.

2. Diagnosis

   i. The ANA test is useful in the evaluation of patients suspected of having systemic lupus erythematosus, drug-induced lupus, or mixed connective tissue disease where a moderate pretest probability is estimated based on the clinical criteria present.

   ii. A positive test, while nonspecific, increases the post-test probability of disease.

   • A positive ANA test (titer> 1:40) should be followed up with more specific tests such as anti-nDNA and precipitating antibodies (against RNP, Sm, Ro/SS-A).

   • However, in a patient over 70 years of age, a titer of 1:40 may be insignificant, and repeat measurement should be obtained to see if the titer increases or is stable.

   iii. A negative ANA test result is extremely powerful in reducing the probability of these diseases.

   • In patients who have high probability of systemic lupus erythematosus based on clinical criteria but who have a negative antinuclear antibody assay, a determination for anti-Ro or antiphospholipid antibodies may be helpful.

3. Monitoring

   i. Repeat measurements of antinuclear antibodies were not indicated in patients in whom connective tissue disease is not suspected.

   ii. The ANA test can be used as an aid in the assessment of systemic lupus erythematosus disease activity and as a guide for treatment.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The HLA-B27 test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference ranges for age and sex.

   ii. The use of the HLA-B27 as a screening test for ankylosing spondylitis in patients presenting with low-back pain will result in a low diagnostic yield.

2. Diagnosis

   i. The HLA-B27 test is not useful for confirmation of the diagnosis of spondyloarthropathies (e.g., ankylosing spondylitis and Reiter’s syndrome) when adequate clinical and radiologic criteria are present.

   ii. However, the HLA-B27 test may be useful in patients with low-back pain of insidious onset, minimal tenderness over the sacroiliac joints, normal spinal movement and chest expansion and equivocal radiographic findings where the pretest probability is close to 50 percent for ankylosing spondylitis.

   • A positive HLA-B27 test increases the likelihood of ankylosing spondylitis significantly and a negative result lowers the likelihood.

   iii. The HLA-B27 test may be useful in children with spondyloarthropathy, especially those with a history of juvenile chronic polyarthritis, to help establish the diagnosis of ankylosing spondylitis.

   iv. The HLA-B27 test may be useful in helping to differentiate incomplete Reiter’s syndrome from seronegative rheumatoid arthritis and gonococcal arthropathy.

3. Monitoring

   i. The HLA-B27 test is not useful for monitoring spondyloarthropathies including the establishment of prognosis, genetic counseling, and patient management.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case Finding

   i. The CRP is not indicated in asymptomatic persons.

   ii. The CRP test should be used selectively and interpreted with caution in patients with symptoms that are not explained by a careful history and physical examination.

   • Significant infections or inflammatory or neoplastic disease is unlikely in such patients, and the CRP must be markedly elevated or positive to be diagnostically useful.

2. Diagnosis

   i. Measurement of CRP by quantitative methods provides the most clinically useful information.

   ii. The CRP is useful for the diagnosis of temporal arteritis (giant cell arteritis) and polymyalgia rheumatica.

   iii. A CRP test may be indicated in patients suspected of rheumatoid arteritis where clinical examination findings are equivocal.

   iv. Measurement of CRP may be useful in the differential diagnosis of peripheral joint pain.

   v. The CRP may be indicated in the differential diagnosis of solitary bone lesions.

   vi. The CRP may be indicated in the diagnosis of metastatic breast cancer.

   vii. The CRP may be indicated as a means of excluding suspected vertebral osteomyelitis.

   viii. The CRP may assist in the differential diagnosis of certain infectious, inflammatory, and malignant disorders.

   ix. The CRP may provide assistance in distinguishing spinal pain of organic from mechanical origin.

3. Monitoring

   i. Measurement of CRP by quantitative methods provides the most clinically useful information.

   ii. The CRP is indicated for monitoring temporal arteritis and polymyalgia rheumatica.

   iii. The judicious use of the CRP test combined with other clinical and laboratory observations may be of value in patients with rheumatoid arthritis and systemic lupus erythematosus.

   iv. The CRP may be indicated for monitoring patients with Hodgkin’s disease.

   v. The CRP may be indicated for monitoring patients with acute rheumatic fever.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. A serum potassium test is not indicated in asymptomatic individuals whose history and physical examination are within reference limits for age and sex.

   ii. Measurement of serum potassium levels is not useful in general screening of ambulatory care patient populations.

2. Diagnosis

   i. Serum potassium measurement is useful in patients with chronic renal disease, including diabetic renal insufficiency.

   ii. Serum potassium measurement is useful in patients with hypertension to detect primary hyper-aldosteronism.

   • Measurements should be made at time of diagnosis and before initiation of care.

   iii. Serum potassium measurement is useful in patients with symptoms or signs suggestive of renal tubular acidosis.

   iv. Serum potassium measurement is useful in patients with signs and symptoms suggestive of altered serum potassium concentration, including generalized or proximal weakness, new atrial tachyarrhythmias, nocturia, polyuria, or ileus.

3. Monitoring

   i. Serum potassium measurement is indicated one to two times a year in patients with diabetic renal disease.

   ii. Serum potassium measurement is indicated in hypertensive patients receiving diuretic therapy.

   iii. Serum potassium measurement may be useful every six months in diuretic-treated patients concurrently receiving digitalis.

   iv. Serum potassium measurements may be useful in patients with renal dysfunction, cardiac arrhythmias, diarrhea, dehydration, and metabolic acidosis in whom there is a change in clinical status.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening

   i. A serum sodium test is not indicated in asymptomatic individuals whose history and physical examination are within reference limits for age and sex.

   ii. Measurement of serum sodium levels is not useful in general screening of ambulatory care patient populations.

2. Diagnosis

   i. Serum sodium measurement may be indicated in patients with the following signs or symptoms:

   • Rapid change in weight
   • Rapid change in fluid balance (severe vomiting, diarrhea, polyuria)
   • Rapid change in mental status
   • Clinical evidence of dehydration or volume depletion

   ii. Serum sodium concentration is not indicated in hypertensive patients to identify primary aldosteronism.

3. Monitoring

   i. Serum sodium measurement may be useful as an index of hydration, especially in elderly persons or others who may fail to ingest adequate quantities of water to maintain water balance.

   ii. Serum sodium measurement may be useful in patients with chronic renal insufficiency at the following frequencies:

   • At the time of change in clinical status
   • When serum creatinine reaches 7 to 8 mg/dL; thereafter, every two to three months

   iii. Serum sodium measurement may be indicated in most patients at the time of change in clinical status, especially change in mental or neurologic status, fluid balance, weight, or dehydration or volume depletion.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum iron and total iron binding capacity (TIBC) tests are not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. In individuals with a moderate to high pretest probability of iron deficiency (e.g., pregnant women, premenopausal female with hemorrhagia, premature infants, and the malnourished) a serum iron and TIBC may be useful.

   iii. Measurement of serum iron and TIBC may be useful in screening for iron overload.

2. Diagnosis

   i. Measurement of serum iron and TIBC are useful in patients whose complete blood count results are consistent with a microcytic hypochromic anemia.

   • Calculation of transferrin saturation from the serum iron and TIBC may provide additional diagnostic information.

   ii. Patients who present with clinical features of iron deficiency may benefit from measurement of serum iron and TIBC tests.

   iii. Serum iron and TIBC measurements may be useful in the differential diagnosis of microcytic hypochromic anemias.

   iv. Measurement of serum iron and TIBC may be useful in the confirmation of iron overload.

3. Monitoring

   i. Measurement of serum iron and TIBC have limited value in monitoring the management of patients with iron deficiency anemia.

   ii. A complete blood count (CBC) and an absolute reticulocyte count are useful tests to monitor the management of iron-deficiency anemia.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. Screening with fecal occult blood tests is not indicated for asymptomatic patients under 40 years of age.

   ii. For persons 40 years and older who have familial polyposis coli, inflammatory bowel disease, or a history of colon cancer in a first-degree relative, screening with fecal occult blood tests is recommended annually.

   • Due to the nature of gastrointestinal bleeding, it is recommended that three consecutive samples be obtained.

   • Screening for colorectal cancer with air-contrast barium enema or colonoscopy in addition to annual fecal occult blood tests is recommended every 3 to 5 years.

   iii. Screening with fecal occult blood tests is recommended annually for persons 50 years of age and older.

   iv. Every 3 to 5 years, in addition to the annual fecal occult blood test, a sigmoidoscopic examination should be performed.

2. Diagnosis

   i. Patients with significant colorectal symptoms (abdominal pain, localized tenderness, diarrhea or constipation, gastrointestinal bleeding) should have a fecal occult blood test performed as part of a colorectal examination.

   ii. A fecal occult blood test result should be interpreted with caution.

   • The influence of diet and nutritional supplements (Vitamin C and iron) should be considered as possible causes of false-positive and false-negative results.

   • Further evaluation of patients with a positive occult blood test may include an air contrast barium enema plus colonoscopy.

   Rating:	Established
   Evidence:	Class II, III
   Consensus Level:	1

   
   

1. Outpatient Screening/Case-Finding

   i. The serum ferritin test is not indicated in asymptomatic individuals whose history and physical examination findings are within reference limits for age and sex.

   ii. In individuals with a moderate to high pretest probability of iron deficiency and with CBC and serum iron/TIBC levels within reference ranges, the serum ferritin test may be useful in detecting the early stages of iron depletion.

2. Diagnosis

   i. Measurement of serum ferritin is useful in anemic patients who are suspected of having iron depletion but have equivocal serum iron and TIBC test results.

   ii. Serum ferritin measurements may be useful in the differentiation of anemia of chronic disease from iron deficiency anemia.

   • A CRP determination should be performed along with serum ferritin to identify possible effects of chronic disease state on ferritin results.

   iii. Measurement of serum ferritin may be useful in the detection of iron overload.

3. Monitoring

   i. Serum ferritin measurement may be useful in the determination of the end-point to oral iron therapy.

   ii. Measurement of serum ferritin may be useful in monitoring iron status of patients with chronic renal disease.

   iii. Serum ferritin measurement may be useful in monitoring the rate of iron accumulation in iron overload.

   Rating:	Established
   Evidence:	Class I, II, III
   Consensus Level:	1