Endocrine Abstracts

Background: Persistent Hypoparathyroidism (PH) is a condition characterized by inappropriately low concentrations of PTH that lead to hypocalcemia. The treatment cornerstones of PH are calcium and calcitriol supplementation; however, several patients do not achieve adequate control of the disease under this conventional therapy. Notably, no biomarker of risk of ‘resistance’ has yet been identified. Based on the fact that obesity alters the vitamin D-calcium homeostasis, inducing hypovitaminosis D and secondary hyperparathyroidism, and that body mass index (BMI) is inversely correlated with circulating levels of vitamin D (VD), we hypothesized that increased BMI could represent a biomarker of resistance to conventional therapy in PH.

Methods: To test our hypothesis we retrospectively evaluated the anthropometric characteristics assessed at PH diagnosis, in 84 consecutive patients (79 with post-surgical, 5 with autoimmune PH). All patients were followed for at least one year, and were under stable conventional treatment with active vitamin D analog and calcium from at least six months. In keeping with recent literature, patients were defined as resistant to calcitriol, if taking ≥1 μg calcitriol/day; and resistant to calcium, if taking ≥1500 mg calcium/day.

Results: We found that BMI was higher in VD resistant patients when compared to VD sensitive (28±5 vs 25±5 kg/m², P<0.02). In contrast, we found no difference in BMI between calcium resistant and calcium sensitive patients (28±6 vs 26±5 kg/m², P=NS). Furthermore, logistic regression analysis showed that BMI was independently associated with resistance to VD therapy (OR 1.13, 95% CI 1.02–1.26; P=0.02), in face of similar serum calcium levels obtained by therapy (8.7 vs 8.9 mg/dl, P=NS). Conversely, logistic regression analysis did not show any association between BMI and resistance to calcium therapy.

Discussion: This is the first study showing that increased BMI at diagnosis can predict the amount of active VD supplementation, but not the amount of calcium supplementation, in PH. The fact that obesity is associated with active VD resistance, but not with calcium resistance, on the one hand, supports previous evidences on a role of excess adipose tissue in the alteration of VD metabolism; and on the other hand, suggests that obesity does not impair calcium absorption and handling, and that patients on high calcium supplementation do not have lower BMI, as previously proposed. Hence, our work proposes BMI as a biomarker of resistance to active VD therapy in PH; and proposes weight loss as a therapeutic strategy to reduce resistance to active VD.