Effect of vitamin D nutrition on parathyroid adenoma weight: Pathogenetic and clinical implications

In primary hyperparathyroidism, adenoma size is a major determinant of dise ase severity and manner of presentation, but the reason for the large varia tion in size (> 100-fold) is unknown. One factor could be the level of vita min D nutrition, because in India, where vitamin D deficiency is endemic, a denomas are larger and the disease more severe than in the U.S. Accordingly , we determined the relationship between vitamin D nutrition, as measured b y serum levels of 25-hydroxyvitamin D (250HD), and parathyroid gland weight , expressed on a logarithmic scale, in 148 U.S. patients with primary hyper parathyroidism. A significant inverse relationship was found between log gland weight; as d ependent variable and serum 250HD as independent variable (r = -0.365; P < 0.0001). The only other influence on gland weight was a weak inverse correl ation with age. Log gland weight as an independent variable was significant ly related to adjusted calcium, PTH, and alkaline phosphatase (AP) as depen dent variables. In 51 patients with serum 250HD levels less than 15 ng/mL, gland weight, PTH, AP, and adjusted calcium were each significantly higher than in 97 patients with 250HD levels of 15 ng/mL or more, but 1,25-dihydro xyvitamin D levels were similarly increased in both groups. In the former g roup the response of adjust-ed calcium to PTH was blunted, and the response of AP was enhanced, based on significant differences in regression slopes (P = 0.0004 and 0.0022, respectively). Suboptimal vitamin D nutrition stimulates parathyroid adenoma growth by a m echanism unrelated to hypocalcemia or 1,25-dihydroxyvitamin D deficiency an d reduces the calcemic response to PTH, so that a higher PTH level and more parathyroid cells are needed to raise the patient's serum calcium to the l evel corresponding to the increased set-point that is characteristic of the disease. Improved vitamin D nutrition in the population is partly, perhaps largely, responsible for the historical changes in disease severity and ma nner of presentation that have occurred over the last 50 yr.