Analysis of vitamin D status at two academic medical centers and a national reference laboratory: result patterns vary by age, gender, season, and patient location

Abstract

Background: Testing for 25-hydroxyvitamin D [25(OH)D] has increased dramatically in recent years. The present report compares overall utilization and results for 25(OH)D orders at two academic medical centers - one in New York and one in Iowa - in order to characterize the vitamin D status of our inpatient and outpatient populations. Results are also compared to those from a national reference laboratory to determine whether patterns at these two institutions reflect those observed nationally.

Methods: Retrospective data queries of 25(OH)D orders and results were conducted using the laboratory information systems at Weill Cornell Medical College / New York Presbyterian Hospital (WCMC), University of Iowa Hospitals and Clinics (UIHC), and ARUP Laboratories (ARUP). Chart review was conducted for cases with very high or low serum 25(OH)D levels in the WCMC and UIHC datasets.

Results: The majority of tests were ordered on females and outpatients. Average serum 25(OH)D levels were higher in female versus male patients across most ages in the WCMC, UIHC, and ARUP datasets. As expected, average serum 25(OH)D levels were higher in outpatients than inpatients. Serum 25(OH)D levels showed seasonal periodicity, with average levels higher in summer than winter and correlating to regional UV index. Area plots demonstrated a peak of increased 25(OH)D insufficiency / deficiency in adolescent females, although overall worse 25(OH)D status was found in male versus female patients in the WCMC, UIHC, and ARUP datasets. Surprisingly, improved 25(OH)D status was observed in patients starting near age 50. Finally, chart review of WCMC and UIHC datasets revealed over-supplementation (especially of ≥ 50,000 IU weekly doses) in the rare cases of very high 25(OH)D levels. General nutritional deficiency and/or severe illness was found in most cases of severe 25(OH)D deficiency.

Conclusions: 25(OH)D status of patients seen by healthcare providers varies according to age, gender, season, and patient location. Improved 25(OH)D status was observed later in life, a finding that may reflect the previously described increased use of vitamin D-containing supplements in such populations. Severe vitamin D deficiency is much more common than vitamin D toxicity.

Figure 1

25(OH)D immunoassay - orders by institution, age, and sex. A, B. Average number of 25(OH)D orders per month (in six month bins) at WCMC (A) and UIHC (B). Error bars are ± SD. C,D. Total number of orders by patient age and sex (female = red lines; male = blue lines) at WCMC (C; 20 months analyzed) and UIHC (D; 153 months analyzed). Data are binned to 1 yr age intervals.

Figure 2

25(OH)D immunoassay – average concentration by age and sex – results for all ages. Average 25(OH)D results at WCMC (A), UIHC (B), and ARUP (C) by age and sex (female = red lines; male = blue lines). Variability at young and old ages (particularly A and B) may be due to comparatively small n-values (see Figure 1C,D).

Figure 3

25(OH)D immunoassay – average concentration by age and sex – results by decade of life. A,B. Average 25(OH)D results at WCMC (A), UIHC (B), and ARUP (C) by age (in 10 year bins) and sex [female = red circles; male = blue circles]. Error bars are ± SD. * p < 0.05.

Figure 4

25(OH)D immunoassay – average concentration by order month with regional UV index. A,B. Average 25(OH)D results at WCMC (A) and UIHC (B) by sex [female = red circles; male = blue circles] and order month. Error bars are ± SD. C,D. Daily issued UV Index for New York City, NY (C) and Des Moines, IA (D) (see Methods).

Figure 5

25(OH)D immunoassay – results by reference intervals. A. Figure legend showing the colors representing reference intervals used in B through H. An asterisk (*) is indicated next to the >80 ng/mL intervals (blue) in A and B, as this interval often contains too few specimens to be easily visible at this magnification (also evident in C through H). B. Presentation of population data as area plots. For any given group (for example, WCMC female patients age 45 shown here) the percent of patients that fall into specific reference intervals can be represented as a pie chart (B, left example). To the right of the pie chart is a “proportional stacked plot” (B, middle) that shows the same data, but now stacked by color-coded reference intervals (low to high) such that the sum of all areas equals 100%. These data can also be presented as a narrower stacked color-coded “single line” (B, right). Graphing “single line” area plots for all ages (aligned by increasing age) produce the area plots shown below. C-H. Area plots show the reference interval distributions for all ages (0–100 yrs; 1 yr bins) in females (C,E,G) and males (D, F, H) at WCMC (C,D), UIHC (E,F) and ARUP (G,H). The UIHC dataset does not include any males greater than 97 years old (F). Overlying reference lines (dotted) have been added at 20% intervals to all area plots (C-H) to facilitate comparison across graphs.

Figure 6

25(OH)D by LC-MS/MS - WCMC dataset. A. 25(OH)D immunoassay results versus LC-MS/MS total 25(OH)D results in cases where both tests were ordered by clinicians on the same specimen. Deming regression (red dashed line) shows a slope of 0.958 and a Y-intercept of 4.7 ng/ml. B. Corresponding fractionated 25(OH)D₂ and 25(OH)D₃ results from specimens ordered for 25(OH)D testing by LC-MS/MS from WCMC. See Results section for n-values. Many data points are obscured due to overlapping position. Both X- and Y-axes are cropped at 100 ng/ml to improve visibility. Red dots (many overlapping) = unquantifiable 25(OH)D₂, quantifiable 25(OH)D₃. Green dots = quantifiable 25(OH)D₂, unquantifiable 25(OH)D₃. Black dot (overlapping) = unquantifiable 25(OH)D₂ and unquantifiable 25(OH)D₃. Blue dots = quantifiable 25(OH)D₂ and quantifiable 25(OH)D₃. C,D. Average 25(OH)D₂ (gray line) and average 25(OH)D₃ (magenta line) results age and sex (C, females; D, males) at WCMC. Variability may be due to comparatively small n-values as shown by specimen counts in each 1 yr bin (E, females; F, males). G,H. Area plots show the reference interval distributions for all ages (1–90 yrs; 1 yr bins) in females (G) and males (H) at WCMC. Figure legend (color) for area plots is identical to Figure 5A.