Clinical Use of Vitamin D Assays
In this issue of the Warde Report, Dr. MacFarlane reviews the physiology of vitamin D metabolism. This is a particularly timely topic as a recent article and accompanying editorial in the New England Journal of Medicine notes that it is important to remember that all children need calcium and vitamin D (Thacher et al., NEJM 1999;341:563.). The vitamin D produced in the skin due to the effect of sunlight is key to normal vitamin D intake. We also obtain vitamin D from food and dietary supplements. Vitamin D must be converted to its active metabolite 1,25-dihydroxyvitamin D by a two-site conversion process. First the liver produces 25-hydroxyvitamin D and the kidney completes the conversion to 1,25-dihydroxyvitamin D. A combination of dietary factors, sunlight, calcium and genetic variants of the vitamin D receptor all affect the process of bone mineral density (Bishop, N. NEJM 1999;341:602.).
The quantity of both metabolites that can be measured in the peripheral blood will vary with the amount of sun exposure, the dietary content and the patient’s clinical condition. Both decreased and increased concentrations of vitamin D can produce clinical problems. Indeed, since vitamin D is stored in the body, one may accumulate too much due to excessive ingestion of vitamin supplements. Patients with impaired production due to lack of sun exposure, liver or renal disease will have decreased levels of 25-hydroxyvitamin D and may also have decreased levels of 1,25-dihydroxyvitamin D. Patients who have chronic renal failure will have normal or low levels of 25-hydroxyvitamin D, but the levels of 1,25-dihydroxyvitamin D will be decreased due to the inability of the kidneys to effectively hydroxylate the 25-hydroxy form.
Granulomatous diseases, such as sarcoidosis and Crohn’s disease with hypercalcemia may be associated with elevated levels of 1,25-dihydroxyvitamin D despite having normal quantities of 25-hydroxyvitamin D. Interestingly, a recent report by Bosch demonstrated a correlation between 1,25-dihydroxyvitamin D levels, serum calcium levels and clinical activity in Crohn’s disease (Gastroent 1998;114:1061.).
Vitamin D supplementation is becoming more common. In the elderly, low levels of 25-hydroxyvitamin D have been found in women with hip fractures prompting the suggestion by LeBoff et al that diet supplementation with vitamin D should be used both to reduce hip fracture risk and to facilitate repair (JAMA 1999;281:1505). Yet, excessive ingestion of vitamin D can lead to elevated levels of either form, depending on the ingested form and concomitant exposure to sunlight. This may produce hypercalcemia with its attendant symptoms of polyuria, polydipsia, nausea, vomiting and diarrhea. These symptoms should prompt a review of ingestion of over-the-counter vitamin supplements and quantification of vitamin D levels in serum.
Throughout the world, children are among the major victims of vitamin D insufficiency, especially in underdeveloped countries and in areas of the world with long cold periods. Still, in practical terms, Bishop’s recent editorial on this subject (cited above) sums it up the best. “Wherever children live, they should follow Grandma’s advice: drink up your milk, and go play outside.”