Temporal Relationship between Vitamin D Status and Parathyroid Hormone in the United States

BACKGROUND: Interpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season. OBJECTIVE: Characterize the temporal relationship between 25-hydroxyvitamin D(3) levels [25(OH)D(3)] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D(2) [25(OH)D(2)] levels with PTH levels and total 25(OH)D levels. METHOD: We retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D(2) and 25(OH)D(3)] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D(3) 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)D(2) (≥4 ng/mL). FINDINGS: Seasonal variation was observed for all genders and latitudes. 25(OH)D(3) peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D(3), 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)D(3) seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D(2) had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D(2). INTERPRETATION: 25(OH)D(3) and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D(2) treated patients; 25(OH)D(3), 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)D(2), and thus are applicable for patient care.