(Medicare National Coverage Determinations Manual)

190.19 - Collagen Crosslinks, Any Method  (Rev. 17, Issued: 07- 02-04) (Effective/Implementation: Not Applicable) PM AB -02-110  Collagen crosslinks, part of the matrix of bone upon which bone mineral is deposited, are biochemical markers the excretion of which provides a quantitative measurement of bone resorption.  Elevated levels of urinary collagen crosslinks indicate elevated bone resorption.  Elevated bone resorption contributes to age -related and postmenopausal loss of bone leading to osteoporosis and increased risk of fracture.  The collagen crosslinks assay can be performed by immunoassay or by high performance liquid chroma tography (HPLC).  Collagen crosslink immunoassays measure the pyridinoline crosslinks and associated telopeptides in urine.   Bone is constantly undergoing a metabolic process called turnover or remodeling.  This includes a degradation process, bone resorpt ion, mediated by the action of osteoclasts, and a building process, bone formation, mediated by the action of osteoblasts.  Remodeling is required for the maintenance and overall health of bone and is tightly coupled; that is, resorption and formation must  be in balance.  In abnormal states of bone remodeling, when resorption exceeds formation, it results in a net loss of bone.  The measurement of specific, bone- derived resorption products provides analytical data about the rate of bone resorption.  Osteoporosis is a condition characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist.  The term primary osteoporosis is applied where the causal  factor in the disease is menopause or aging.  The term secondary osteoporosis is applied where the causal factor is something other than menopause or aging, such as long- term administration of glucocorticosteroids, endocrine -related disorders (other than loss of estrogen due to menopause), and certain bone diseases such as cancer of the bone.   With respect to quantifying bone resorption, collagen crosslink tests can provide adjunct diagnostic information in concert with bone mass measurements.  Bone mass measurements and biochemical markers may have complementary roles to play in assessing effectiveness of osteoporosis treatment.  Proper management of osteoporosis patients, who are on long -term therapeutic regimens, may include laboratory testing of biochem ical markers of bone turnover, such as collagen crosslinks, that provide a profile of bone turnover responses within weeks of therapy.  Changes in collagen crosslinks are determined following commencement of antiresorptive therapy.  These can be measured over a shorter time interval, such as three months, when compared to bone mass density.  If bone resorption is not elevated, repeat testing is not medically necessary.   Indications   Generally speaking, collagen crosslink testing is useful mostly in fast losers of bone.  The age when these bone markers can help direct therapy is often pre -Medicare.  By the time a fast loser of bone reaches age 65, she will most likely have been stabilized by appropriate therapy or have lost so much bone mass that further te sting is useless.  Coverage for bone marker assays may be established, however, for younger Medicare beneficiaries and for those men and women who might become fast losers because of some other therapy such as glucocorticoids.  Safeguards should be incorpo rated to prevent excessive use of tests in patients for whom they have no clinical relevance.   Collagen crosslinks testing is used to:   1. Identify individuals with elevated bone resorption, who have osteoporosis in whom response to treatment is being monitor ed.  2. Predict response (as assessed by bone mass measurements) to FDA approved antiresorptive therapy in postmenopausal women.   3. Assess response to treatment of patients with osteoporosis, Pagets disease or the bone, or risk for osteoporosis where treatment  may include FDA approved antiresorptive agents, anti -estrogens or selective estrogens receptor moderators.   Limitations   Because of significant specimen to specimen collagen crosslink physiologic variability (15-20 percent), current recommendations for appropriate utilization include: one or two base- line assays from specified urine collections on separate days; followed by a repeat assay about 3 months after starting anti -resorptive therapy; followed by a repeat assay in 12 months af ter the 3 -month assay; and thereafter not more than annually, unless there is a change in therapy in which circumstance an additional test may be indicated 3 months after the initiation of new therapy.   Some collagen crosslink assays may not be appropriate  for use in some disorders, according to FDA labeling restrictions.  190.20 - Blood Glucose Testing  (Rev. 28, Issued: 02- 11-05, Effective:  01 -01-05, Implementation:  03- 11-05)  This policy is intended to apply to blood samples used to determine glucose le vels.  Blood glucose determination may be done using whole blood, serum or plasma.  It may be sampled by capillary puncture, as in the fingerstick method, or by vein puncture or arterial sampling.  The method for assay may be by color comparison or an indi cator stick, by meter assay of whole blood or a filtrate of whole blood, using a device approved for home monitoring, or by using a laboratory assay system using serum or plasma.  The convenience of the meter or stick color method allows a patient to have access to blood glucose values in less than a minute or so and has become a standard of care for control of blood glucose, even in the inpatient setting.  Indications   Blood glucose values are often necessary for the management of patients with diabetes mellitus, where hyperglycemia and hypoglycemia are often present.  They are also critical in the determination of control of blood glucose levels in the patient with impaired fasting glucose (FPG 110- 125 mg/dL), the patient with insulin resistance syndrome a nd/or carbohydrate intolerance (excessive rise in glucose following ingestion of glucose or glucose sources of food), in the patient with a hypoglycemia disorder such as nesidioblastosis or insulinoma, and in patients with a catabolic or malnutrition state .  In addition to those conditions already listed, glucose testing may be medically necessary in patients with tuberculosis, unexplained chronic or recurrent infections, alcoholism, coronary artery disease (especially in women), or unexplained skin conditi ons (including pruritis, local skin infections, ulceration and gangrene without an established cause).   Many medical conditions may be a consequence of a sustained elevated or depressed glucose level.  These include comas, seizures or epilepsy, confusion, abnormal hunger, abnormal weight loss or gain, and loss of sensation.  Evaluation of glucose may also be indicated in patients on medications known to affect carbohydrate metabolism.   Effective January 1, 2005, the Medicare law expanded coverage to diabeti c screening services.  Some forms of blood glucose testing covered under this national coverage determination may be covered for screening purposes subject to specified frequencies.  See 42 CFR 410.18 and section 90, chapter 18, of the Claims Processing Ma nual, for a full description of this screening benefit.   Limitations   Frequent home blood glucose testing by diabetic patients should be encouraged.  In stable, non- hospitalized patients who are unable or unwilling to do home monitoring, it may be reasonab le and necessary to measure quantitative blood glucose up to four times annually.  Depending upon the age of the patient, type of diabetes, degree of control, complications of diabetes, and other co -morbid conditions, more frequent testing than four times annually may be reasonable and necessary.   In some patients presenting with nonspecific signs, symptoms, or diseases not normally associated with disturbances in glucose metabolism, a single blood glucose test may be medically necessary.  Repeat testing may not be indicated unless abnormal results are found or unless there is a change in clinical condition.  If repeat testing is performed, a specific diagnosis code (e.g., diabetes) should be reported to support medical necessity.  However, repeat testing may be indicated where results are normal in patients with conditions where there is a confirmed continuing risk of glucose metabolism abnormality (e.g., monitoring glucocorticoid therapy).   190.21 - Glycated Hemoglobin/Glycated Protein  (Rev. 17, Issued: 07 -02-04) (Effective/Implementation: Not Applicable) PM AB -02-110  The management of diabetes mellitus requires regular determinations of blood glucose levels.  Glycated hemoglobin/protein levels are used to assess long- term glucose control in diabetes.  Alternative names for these tests include glycated or glycosylated hemoglobin or Hgb, hemoglobin glycated or glycosylated protein, and fructosamine.  Glycated hemoglobin (equivalent to hemoglobin A1) refers to total glycosylated hemoglobin present in erythrocytes, usually determined by affinity or ion- exchange chromatographic methodology.  Hemoglobin A1c refers to the major component of hemoglobin A1, usually determined by ion- exchange affinity chromatography, immunoassay or agar gel electrophoresis.  Fructosamine or glycated protein refers to glycosylated protein present i n a serum or plasma sample.  Glycated protein refers to measurement of the component of the specific protein that is glycated usually by colorimetric method or affinity chromatography.   Glycated hemoglobin in whole blood assesses glycemic control over a pe riod of 4- 8 weeks and appears to be the more appropriate test for monitoring a patient who is capable of maintaining long- term, stable control.  Measurement may be medically necessary every 3 months to determine whether a patients metabolic control has be en on average within the target range.  More frequent assessment, every 1 -2 months, may be appropriate in the patient whose diabetes regimen has been altered to improve control or in whom evidence is present that intercurrent events may have altered a prev iously satisfactory level of control (for example, post -major surgery or a s a result of glucocorticoid therapy).  Glycated protein in serum/plasma assesses glycemic control over a period of 1 -2 weeks.  It may be reasonable and necessary to monitor glycate d protein monthly in pregnant diabetic women.  Glycated hemoglobin/protein test results may be low, indicating significant, persistent hypoglycemia, in nesidioblastosis or insulinoma, conditions which are accompanied by inappropriate hyperinsulinemia.  A b elow normal test value is helpful in establishing the patients hypoglycemic state in those conditions.  Indications   Glycated hemoglobin/protein testing is widely accepted as medically necessary for the management and control of diabetes.  It is also valuable to assess hyperglycemia, a history of hyperglycemia or dangerous hypoglycemia. Glycated protein testing may be used in place of glycated hemoglobin in the management of diabetic patients, and is particularly useful in patients who have abnormalities of erythrocytes such as hemolytic anemia or hemoglobinopathies.  Limitations   It is not considered reasonable and necessary to perform glycated hemoglobin tests more often than every 3 months on a controlled diabetic patient to determine whether the patient s metabolic control has been on average within the target range.  It is not considered reasonable and necessary for these tests to be performed more frequently than once a month for diabetic pregnant women.  Testing for uncontrolled type one or two diabet es mellitus may require testing more than four times a year.  The above section provides the clinical basis for those situations in which testing more frequently than four times per annum is indicated, and medically necessary documentation must support suc h testing in excess of the above guidelines.  Many methods for the analysis of glycated hemoglobin show significant interference from elevated levels of fetal hemoglobin or by variant hemoglobin molecules.  When the glycated hemoglobin assay is initially performed in these patients, the laboratory may inform the ordering physician of a possible analytical interference.  Alternative testing, including glycated protein, for example, fructosamine, may be indicated for the monitoring of the degree of glycemic c ontrol in this situation.  It is therefore conceivable that a patient will have both a glycated hemoglobin and glycated protein ordered on the same day.  This should be limited to the initial assay of glycated hemoglobin, with subsequent exclusive use of glycated protein.  These tests are not considered to be medically necessary for the diagnosis of diabetes.   190.22 - Thyroid Testing  (Rev. 17, Issued: 07- 02-04) (Effective/Implementation: Not Applicable) PM AB -02-110  Thyroid function studies are used to de lineate the presence of absence of hormonal abnormalities of the thyroid and pituitary glands.  These abnormalities may be either primary or secondary and often but not always accompany clinically defined signs and symptoms indicative of thyroid dysfunction.  Laboratory evaluation of thyroid function has become more scientifically defined.  Tests can be done with increased specificity, thereby reducing the number of tests needed to diagnose and follow treatment of most thyroid disease.  Measurements of serum sensitive thyroid- stimulating hormone (TSH) levels, complemented by determination of thyroid hormone levels [free thyroxine (fT -4) or total thyroxine (T4) with Triiodothyronine (T3) uptake] are used for diagnosis and follow -up of patients with thyroid di sorders.