Vitamin D Supplementation in Primary Hyperparathyroidism: Analysis of Benefits and Hazards

Primary hyperparathyroidism (PHPT) and vitamin D deficiency (VD) are two frequent medical conditions in the Western world. Purely by dint of their prevalence, these conditions are commonly comorbid. Moreover, they can interact with one another: VD may stimulate PTH secretion, while PHPT may lead to unregulated vitamin D activation from 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25OH2D), thereby lowering 25OHD levels and further exacerbating VD. Thus, a real conundrum arises: should the careful clinician replete VD in PHPT or not? On the one hand, both conditions could lead to bone mineral density (BMD) loss if untreated, ultimately resulting in osteoporosis and fragility fractures; on the other hand, vitamin D supplementation could lead to further worsening of hypercalcemia and its dreaded complications. To complicate matters, patients undergoing parathyroidectomy (PTX) after long-standing PHPT can also suffer from postoperative hungry-bone syndrome and symptomatic hypocalcemia, which may be further exacerbated by VD. This narrative review aims to summarize the relevant pathophysiological mechanisms underlying these two diseases and their complex interactions. The latest evidence regarding thresholds and targets for vitamin D supplementation in PHPT will be discussed, with a focus on the balance between benefits and risks.