LCD L39391: Vitamin D Assay Testing

This Local Coverage Determination (LCD) identifies the indications and limitations of Medicare coverage and reimbursement for Vitamin D laboratory assays in the medical management of patients.

For Medicare beneficiaries, screening tests are governed by statute. Reimbursement is not allowed for routine screening for vitamin D deficiency in asymptomatic individuals and/or during general encounters.

Although it is not the active form of the hormone, 25-OH vitamin D is much more commonly measured because it better reflects the sum total of vitamin D produced endogenously and absorbed from the diet than does the level of the active hormone 1,25-dihydroxy vitamin. 25-hydroxyvitamin D [25(OH)D] testing will be considered medically reasonable and necessary for individuals at risk for deficiency with the following conditions:

• Chronic kidney disease (CKD) stage III or greater

• Cystic Fibrosis (CF)

• Cirrhosis

• Crohn’s disease

• Gastric bypass/bariatric surgery

• Granuloma forming diseases

• Hyperalimentation

• Hypocalcemia

• Hypercalcemia

• Hypercalciuria

• Hypervitaminosis D

• Hypovitaminosis D

• Inflammatory bowel disease

• Long term use of medications known to lower vitamin d levels: anticonvulsants, antiretroviral therapy, glucocorticoids, antifungals, and cholestyramine

• Parathyroid disorders

• Paget’s disease of bone

• Obesity, if Body Mass Index (BMI) ≥ 30 kg/m2

• Obstructive jaundice

• Osteomalacia

• Osteopenia

• Osteoporosis

• Osteosclerosis/petrosis

• Pregnant and lactating women

• Radiation enteritis

• Rickets

• Vitamin D deficiency on replacement therapy related to a condition listed above, to monitor the efficacy of treatment

Deficiency of 1,25-dihydroxy vitamin D, which is present at much lower concentrations, does not necessarily reflect deficiency of 25-OH vitamin D and its measurement should be limited to specific clinical situations. It will be considered reasonable and necessary for patients with the following conditions:

• Unexplained hypercalcemia

• Unexplained hypercalciuria

• Suspected genetic childhood rickets

• Suspected tumor induced osteomalacia

• Nephrolithiasis

• Renal osteodystrophy

• Sarcoidosis

Once a beneficiary has been shown to be vitamin D deficient with a serum level of

If, after a 12-week period of supplementation and documentation of compliance with the prescribed supplementation, the serum level is still

Thereafter, annual testing may be appropriate depending upon the indication and other mitigating factors. The documentation must support the need for annual testing. Annual testing should be rare.

Vitamin D is a fat-soluble vitamin appreciated for its role in calcium homeostasis and bone health. It consists of 2 bioequivalent forms: Vitamin D2 (D2), also known as ergocalciferol, and Vitamin D3 (D3), also known as cholecalciferol. D2 is obtained from dietary vegetable sources and oral supplements. D3 is obtained primarily from skin exposure to ultraviolet radiation in sunlight, but also ingestion of food sources such as oily fish and variably fortified foods (milk, juices, margarines, yogurts, cereals, and soy), and oral supplements. Both D2 and D3 are biologically inert. Once absorbed from the intestine, they are metabolized in the liver to 25-hydroxyvitamin D [25(OH)D], composed of 25(OH)D2 and 25(OH)D3. 25(OH)D (also called calcidiol) is then subsequently converted to 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol, in the kidney and select other tissues by the action of the 1α-hydroxylase enzyme. This enzyme in the kidney is regulated by nearly every hormone involved in calcium homeostasis. Its activity is stimulated by parathyroid hormone (PTH), estrogen, calcitonin, prolactin, growth hormone, low calcium levels, and low phosphorus levels and inhibited by calcitriol, thus providing a feedback loop. 1

Lack of vitamin D activity leads to reduced intestinal absorption of calcium and phosphorus. Early in vitamin D deficiency, hypophosphatemia is more marked than hypocalcemia. With persistent vitamin D deficiency, hypocalcemia occurs and causes secondary hyperparathyroidism, which leads to phosphaturia, demineralization of bones, and, when prolonged and severe, to osteomalacia in adults and rickets in children. The incidence of osteomalacia in the United States (U.S.) is rare. Bolland et.al. reviewed over 42,000 25(OH)D measurements in 32,386 individuals. Only 9 met the criteria for a diagnosis of osteomalacia (0.02%). 2

D3 production in the skin is exceedingly efficient. It is estimated that brief casual exposure of the arms and face is equivalent to ingestion of 200 international units per day. However, the length of daily exposure required to obtain the sunlight equivalent of oral vitamin D supplementation is difficult to predict on an individual basis and varies with the skin type, sunscreen use, latitude, season, and time of day. At northern latitudes, there is not enough radiation to produce vitamin D, particularly during the winter. 3 Sunlight also induces production of melanin, which reduces production of vitamin D3 in the skin. Infants, disabled persons, and older adults may have inadequate sun exposure. The skin of those older than 70 years of age does not convert vitamin D efficiently. For these reasons, in the U.S., milk, infant formula, breakfast cereals, and some other foods are fortified with synthetic vitamin D2 (ergocalciferol), which is derived from radiation of ergosterol found in plants, the mold ergot, and plankton, or with vitamin D3. In other parts of the world, cereals and bread products are often fortified with vitamin D. 4

Vitamin D toxicity, though rare, may cause hypercalciuria, hypercalcemia, renal stones, and renal calcification with renal failure. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of at least 40,000 IU/d with a serum level of 25 (OH)D of at least 88ng/ml, most being 150- 250 ng/ml. Vitamin D intoxication generally occurs after inappropriate use of vitamin D preparations. It may occur in fad dieters who consume "mega doses" of supplements or in patients who take vitamin D replacement therapy for malabsorption, renal osteodystrophy, osteoporosis, or psoriasis. Prolonged exposure of the skin to sunlight does not produce toxic amounts of vitamin D3 (cholecalciferol), due to photoconversion of previtamin D3 and vitamin D3 to inactive metabolites. The rarity of reports of vitamin D toxicity can be explained in part by the kidney's ability to limit production of active calcitriol. Increased calcitriol levels inhibit PTH both directly (through the vitamin D response element on the PTH gene), and indirectly (by increasing intestinal calcium absorption), causing calcitriol production in the kidney to decrease. Renal 24-hydroxylase activity further limits the availability of calcitriol by creating inert metabolites of both calcitriol (1,24,25-trihydroxyvitamin D) and calcidiol (24,25-dihydroxyvitamin D). The 24-hydroxylase gene is under the transcriptional control of calcitriol, thereby providing tight negative feedback. 5