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.