Temporal relationship between vitamin D status and parathyroid hormone in the United States.

Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.Characterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels.We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32-40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (≥4 ng/mL).Seasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2.25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for patient care

Seasonal Variation of 25-Hydroxyvitamin D₃ (bottom panel) and Intact PTH (iPTH) (top panel) Weekly Mean Values.

<p>The maximum seasonal variation of 25(OH)D₃ (peak to trough) was 6.8 ng/mL, reaching its trough in the 8^th week (early March) of each year and its peak in the 34^th week (early September). Peak iPTH values occurred at week 12 (early April) and trough values at week 37 (late September), a pattern that is roughly reciprocal to that of 25(OH)D₃, but lags by 3.5 weeks. Individual points represent the mean of the normalized distribution for each week. The solid lines represent the fit. Dark vertical dashed lines represent 25-hydroxyvitamin D₃ peaks and troughs, and light vertical dashed lines represent the iPTH peaks and troughs. To convert 25-hydroxyvitamin D₃ from ng/mL to nmol/L, multiply by 2.496 (rounded as 2.5).</p

Categorical percentage of patients for total 25(OH)D for all patients who had detectable 25(OH)D₂.

<p>The percentiles are categorized by month. The upper portion (blue) of each month shows the percentage of patients with sufficient 25(OH)D₃; the central portion (yellow), insufficient but not deficient; and the lower portion (red), deficient.</p

Seasonal Variation in Weekly Mean Values of 25-Hydroxyvitamin D₃ (panels A and B) and Intact PTH (iPTH; panels C and D) by Gender and Region.

<p>A. Women show higher average values for 25(OH)D₃ than men. B. North and Central regions show similar average values for 25(OH)D₃ but the South region shows higher average values in winter, even though all three regions show similar values in summer. C. Men show higher average values than women for iPTH. D. The Central region shows the highest average values for iPTH, followed by the Northern region and then the South region.</p

Percentage of patients with elevated iPTH concentrations (>65 pg/mL), by month.

<p>A. All groups. B. The percentage of subjects with iPTH greater than the upper limit of the reference interval (>65 pg/mL) reaches its trough in late summer and its peak in late winter. C. By region and gender. D. Patients with undetectable 25(OH)D₂ E. All patients with detectable 25(OH)D₂, even though the sinusoidal pattern is somewhat diminished, it still fit a sinusoidal function (null hypothesis p<0.001). The seasonal relationship holds across region, gender and presence or absence of detectable 25(OH)D₂. The regions demonstrate similar patterns, but the percentage of subjects with iPTH greater than the reference interval was greater for the central and northern regions than the southern region and greater for men than women.</p

Percentages of patients with 25(OH)D₃ deficiency (<20 ng/mL), insufficiency (20–29 ng/mL), and sufficiency (≥30 ng/mL), by month.

<p>The percentiles are categorized by month. The upper portion (blue) of each month shows the percentage of patients with sufficient 25(OH)D₃; the central portion (yellow), insufficient but not deficient; and the lower portion (red), deficient. The percentage of patients considered deficient or insufficient depends on the season, lower in summer (approximately 50%) and higher in winter (approximately 70%). The sun symbol indicates the summer solstice and the crescent moon symbol, the winter solstice. The central panel shows the seasonal similarity of total 25(OH)D with that of 25(OH)D2. The lower panel shows the rhythmic pattern across regions and gender. The Central and Northern regions were combined because they were similar. Their trough to peak difference is greater than that for the Southern region. Women and men percentages show similar patterns, except that the trough to peak difference is greater for men than women. The sun symbol indicates the summer solstice and the crescent moon, the winter solstice.</p