mp-732 - mp-732 - Medical Policies
Testing Serum Vitamin D Levels
Policy Number: MP-732
Latest Review Date: December 2020
Policy Grade: B
Effective for dates January 1, 2020 and after:
- Serum testing of 25-hydroxyvitamin D levels may be considered medically necessary in patients with a clinically documented underlying disease, condition, or risk factor which is specifically associated with vitamin D deficiency, toxicity, or decreased bone density. These conditions are:
- Biliary cirrhosis and other specified disorders of the biliary tract
- Blind loop syndrome
- Celiac Disease
- Coronary artery disease in individuals where risk of disease progression is being considered against benefits of chronic vitamin D and calcium therapy
- Hypercalcemia, hypocalcemia or other disorders of calcium metabolism
- Hyperparathyroidism or hypoparathyroidism
- Hypervitaminosis of vitamin D
- Individuals receiving hyperalimentation
- Intestinal malabsorption
- Liver cirrhosis
- Long term use of anticonvulsants, glucocorticoids and other medications known to lower vitamin D levels
- Myopathy related to endocrine diseases
- Osteogenesis imperfecta
- Pancreatic steatorrhea
- Primary or miliary tuberculosis
- Regional enteritis
- Renal, ureteral or urinary calculus
- Stage III-V Chronic Kidney Disease and End Stage Renal Disease
- Systemic lupus erythematosus
- Testing for D2 and D3 fractions of 25-hydroxyvutamin D may be considered medically necessary as part of the total 25-hydroxyvutamin D analysis.
- 25-hydroxyvitamin D serum testing is considered not medically necessary for all other medical conditions.
- Repeat testing of serum 25-hydroxyvitamin D levels may be considered medically necessary in individuals who have documented vitamin D deficiency, at least twelve (12) weeks after initiation of vitamin D supplementation therapy.
- Testing of serum 25-hydroxyvitamin D levels more frequently than twice in a rolling twelve (12) month period is considered not medically necessary for any diagnosis other than chronic kidney disease (CKD) or intestinal malabsorption.
- Serum testing of 1, 25-dihydroxyvitamin D levels may be considered medically necessary in the evaluation or treatment of conditions that are associated with defects in vitamin D metabolism. These conditions are:
- Disorders of calcium metabolism
- Familial hypophosphatemia
- Fanconi syndrome
- Hyperparathyroidism or hypoparathyroidism
- Individuals receiving hyperalimentation
- Neonatal hypocalcemia
- Osteogenesis imperfecta
- Primary or miliary tuberculosis
- Renal, ureteral or urinary calculus
- Stage III-V Chronic Kidney Disease and End Stage Renal Disease
- Vitamin D resistant rickets
- Pseudovitamin D-deficiency rickets
- 1, 25-dihydroxyvitamin D serum testing is considered not medically necessary for all other medical conditions.
- 25-hydroxyvitamin D and/or 1, 25-dihydroxyvitamin D serum testing for routine screening of vitamin D deficiency is considered investigational.
Both assays of vitamin D need not be performed for each of the above conditions. Often, one type is more appropriate for a certain disease state than another. The most common type of vitamin D deficiency is 25-OH vitamin D. A much smaller percentage of 1, 25-dihydroxy vitamin D deficiency exists; mostly, in those with renal disease.
DESCRIPTION OF PROCEDURE OR SERVICE:
Vitamin D, also known as calciferol, is a fat-soluble vitamin that has a variety of physiologic effects, most prominently in calcium homeostasis and bone metabolism. In addition to the role it plays in bone metabolism, other physiologic effects include inhibition of smooth muscle proliferation, regulation of the renin-angiotensin system, a decrease in coagulation, and a decrease in inflammatory markers.
Vitamin D, also known as calciferol, is a fat-soluble vitamin that has a variety of physiologic effects, most prominently in calcium homeostasis and bone metabolism. In addition to the role vitamin D plays in bone metabolism, other physiologic effects include inhibition of smooth muscle proliferation, regulation of the renin-angiotensin system, a decrease in coagulation, and a decrease in inflammatory markers.
Vitamin D Levels
Vitamin D deficiency is best assessed by measuring serum levels of 25-hydroxyvitamin D. However, there is no consensus on the minimum vitamin D level or on the optimal serum level for overall health. A 2011 Institute of Medicine (IOM) report concluded that a serum level of 20 ng/mL is sufficient for most healthy adults. Some experts, such as the National Osteoporosis Foundation and the American Geriatrics Society, have recommended a higher level (30 ng/mL). Vitamin D deficiency, as defined by suboptimal serum levels, is common in the United States. In the National Health and Nutrition Examination Survey covering the period of 2000-2004, 30% of individuals over the age of 12 had 25-hydroxyvitamin D levels less than 20 ng/mL. Vitamin D deficiency occurs most commonly as a result of inadequate dietary intake coupled with inadequate sun exposure. Evidence from the National Nutrition Monitoring System and the National Health and Nutrition Examination Survey has indicated that the average consumption is below recommended levels of intake. Yetley (2008) estimated that average daily intake for U.S. adults ranged from 228 to 335 IU/d, depending on gender and ethnicity. This level is below the average daily requirement, estimated by IOM (400 IU/d for healthy adults), and well below IOM’s required daily allowance (estimated to be 600 IU for nonelderly adults and 800 IU for elderly adults).
Vitamin D deficiency may occur less commonly for other reasons. Kidney or liver disease can cause deficiency as a result of the impaired conversion of inactive vitamin D to its active products. In rare situations, there is vitamin D resistance at the tissue level, which causes a functional vitamin D deficiency despite “adequate” serum levels.
The safe upper level for serum vitamin D is also not standardized. The IOM report concluded there is potential harm associated with levels greater than 50 ng/mL and recommended that serum levels be maintained in the 20- to 40-ng/mL range. However, conclusions on this point have differed. A 2011 Agency for Healthcare Research and Quality systematic review of vitamin D and bone health concluded that “There is little evidence from existing trials that vitamin D above current reference intakes is harmful.” The Women’s Health Initiative concluded that hypercalcemia and hypercalciuria in patients receiving calcium and vitamin D were not associated with adverse clinical events. The Women’s Health Initiative did find a small increase in kidney stones for women ages 50 to 79 years who received vitamin D and calcium.
Associations of vitamin D levels with various aspects of health have been noted over the last several decades, and these findings have led to the question of whether supplementation improves health outcomes. For example, a relation between vitamin D levels and overall mortality has been reported in most observational studies examining this association. Mortality is lowest at vitamin D levels in the 25- to 40-nmol/L range. At lower levels of serum vitamin D, mortality increases steeply, and overall mortality in the lowest quintile was more than three times that in the middle quintiles. Theodoratou et al (2014) identified 107 systematic reviews of observational studies examining the association between vitamin D levels and more than 100 different outcomes.
Vitamin D Replacement
The Institute of Medicine has recommended reference values for the intake of vitamin D and serum levels, based on available literature and expert consensus. Recommended daily allowances are 600 IU/d for individuals between one and 70 years of age, and 800 IU/d for individuals older than 70 years.
Estimates of vitamin D requirements are complicated by the many other factors that affect serum levels. Sun exposure is the most prominent of factors that affect serum levels, and this is because individuals can meet their vitamin D needs entirely through adequate sun exposure. Other factors such as age, skin pigmentation, obesity, physical activity, and nutritional status also affect vitamin D levels and can result in variable dietary intake requirements to maintain adequate serum levels.
Excessive intake of vitamin D can be toxic. Toxic effects are usually due to hypercalcemia and may include confusion, weakness, polyuria, polydipsia, anorexia, and vomiting. In addition, high levels of vitamin D may promote calcium deposition and have the potential to exacerbate conditions such as calcium kidney stones and atherosclerotic vascular disease.
The Institute of Medicine defined three parameters of nutritional needs for vitamin D, on the assumption of minimal sun exposure. These parameters were the estimated average requirement, defined as the minimum intake required to maintain adequate levels; the recommended daily allowance, defined as the optimal dose for replacement therapy; and the upper-level intake, defined as the maximum daily dose to avoid toxicity.
The most recent literature update was performed through October 16, 2020.
Summary of Evidence
For individuals who are asymptomatic without conditions or risk factors for which vitamin D treatment is recommended who receive testing of vitamin D levels, the evidence includes no randomized controlled trials (RCTs) of clinical utility (i.e., evidence that patient care including testing vitamin D levels versus care without testing vitamin D levels improves outcomes). Relevant outcomes are overall survival, test validity, symptoms, morbid events, and treatment-related morbidity. Indirect evidence of the potential utility of testing includes many RCTs and systematic reviews of vitamin D supplementation. There is a lack of standardized vitamin D testing strategies and cutoffs for vitamin D deficiency are not standardized or evidence-based. In addition, despite the large quantity of evidence, considerable uncertainty remains about the beneficial health effects of vitamin D supplementation. Many RCTs have included participants who were not vitamin D deficient at baseline and did not stratify results by baseline 25-hydroxyvitamin D level. Nonwhite race/ethnic groups are underrepresented in RCTs but have increased risk of vitamin D deficiency. For skeletal health, there may be a small effect of vitamin D supplementation on falls, but there does not appear to be an impact on reducing fractures for the general population. The effect on fracture reduction may be significant in elderly women, and with higher doses of vitamin D. For patients with asthma, there may be a reduction in severe exacerbations with vitamin D supplementation, but there does not appear to be an effect on other asthma outcomes. For patients who are pregnant, vitamin D supplementation may improve maternal and fetal outcomes. For overall mortality, there is also no benefit to the general population. RCTs evaluating extra skeletal, cancer, cardiovascular, and multiple sclerosis outcomes have not reported a statistically significant benefit for vitamin D supplementation. Although vitamin D toxicity and adverse events appear to be rare, few data on risks have been reported. The evidence is insufficient to determine the effects of the technology on health outcomes.
Vitamin D testing may benefit those at risk for severe deficiency or those with laboratory or radiographic findings commonly associated with vitamin D deficiency in these patients, knowledge of the 25 (OH) D blood level provides an accurate assessment of vitamin D body stores, helps identify the need for vitamin D therapy, and may help to determine an effective dose. There is no evidence-based clinical practice guidelines that recommend screening of persons without a clinically documented underlying disease or condition which is specifically associated with the risk of decreased bone density or osteoporosis.
Practice Guideline and Position Statements
In 2011, The Endocrine Society published clinical practice guidelines on the evaluation, treatment, and prevention of vitamin D deficiency. The following recommendations were made regarding testing vitamin D levels:
- 25-hydroxyvitamin D serum level testing is recommended: “to evaluate vitamin D status only in patients who are at risk of deficiency.” The guideline did not recommend screening of individuals not at risk of vitamin D deficiency.
- 1, 25-dihydroxyvitamin D testing was not recommended to evaluate vitamin D status. However, the guideline did recommend monitoring calcitriol levels under certain conditions.
American College of Obstetrics and Gynecology
The American College of Obstetrics and Gynecology issued a committee opinion (2011, reaffirmed 2017) on the testing of vitamin D levels and vitamin D supplementation in pregnant women. The following recommendation was made concerning testing vitamin D levels:
“At this time there is insufficient evidence to support a recommendation for screening all pregnant women for vitamin D deficiency. For pregnant women thought to be at increased risk of vitamin D deficiency, maternal serum 25-hydroxyvitamin D levels can be considered and should be interpreted in the context of the individual clinical circumstance. When vitamin D deficiency is identified during pregnancy, most experts agree that 1,000-2,000 international units per day of vitamin D is safe.”
American Academy of Family Physicians
The American Academy of Family Physicians supports the U.S. Preventative Task Force recommendation on vitamin D screening.
In 2018, key recommendations for practice concluded that there was insufficient information to recommend screening the general population for vitamin D deficiency and that treating asymptomatic individuals with identified deficiency has not been shown to improve health
U.S. Preventive Services Task Force Recommendations
The U.S. Preventive Services Task Force published a recommendation in 2014, and associated guidelines in 2015, on vitamin D screening. The Task Force concluded that the current evidence was insufficient to assess the balance of benefits and harms of screening for vitamin D deficiency in asymptomatic individuals (grade I [insufficient evidence]). In the 2020 draft of the updated evidence review, the final recommendation upholds the same conclusion; however, the final version is not yet published.
Vitamin D, calciferol, serum levels, 25-hydroxyvitamin D, hypervitaminosis D, 1, 25-dihydroxyvitamin D
APPROVED BY GOVERNING BODIES:
The U.S. Food and Drug Administration (FDA) has cleared a number of immunoassays for in vitro diagnostic devices for the quantitative measurement of total 25-hydroxyvitamin D through the 510(k) process.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments. Lab tests for vitamin D are available under the auspices of the CLIA. Laboratories that offer laboratory-developed tests must be licensed by CLIA for high-complexity testing. To date, the FDA has chosen not to require any regulatory review of this test.
Coverage is subject to member’s specific benefits. Group specific policy will supersede this policy when applicable.
ITS: Home Policy provisions apply
FEP contracts: FEP does not consider investigational if FDA approved and will be reviewed for medical necessity.
Vitamin D, 25 hydroxy D2 and D3, by LC-MS/MS, serum microsample, quantitative (Sensieva™ Droplet 25OH Vitamin D2/D3 Microvolume LC/MS Assay)
Vitamin D; 25 hydroxy, includes fraction(s), if performed
Vitamin D; 1, 25 dihydroxy, includes fraction(s), if performed
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Medical Policy Group, November 2019 (9): New policy
Medical Policy Administration Committee, December 2019
Available for comment November 18, 2019 through January 2, 2020
Medical Policy Panel, December 2020
Medical Policy Group, December 2020 (9): 2020 Updates to Key Points, Description, References. No change to policy statement.
This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.
The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.
As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.
The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:
1. The technology must have final approval from the appropriate government regulatory bodies;
2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;
3. The technology must improve the net health outcome;
4. The technology must be as beneficial as any established alternatives;
5. The improvement must be attainable outside the investigational setting.
Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:
1. In accordance with generally accepted standards of medical practice; and
2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and
3. Not primarily for the convenience of the patient, physician or other health care provider; and
4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.