Secondary and Tertiary Hyperparathyroidism among Patients with X-Linked Hypophosphatemia: A Systematic Review and Meta-analysis.

Hyperparathyroidism (HPT) is an established complication of X-linked hypophosphatemia (XLH). Reports of exacerbations in hypercalcemia among patients with XLH and tertiary hyperparathyroidism (THPT) among those initiating burosumab treatment have renewed interest in the prevalence and consequences of THPT among patients with XLH. This systematic review searched PubMed, Embase, and Web of Science. We included single and multi-center studies of pediatric and adult populations with XLH, provided that the studies reported the prevalence of THPT and did not prescreen and exclude participants with HPT. We estimated the pooled prevalence of THPT in XLH and, for comparison, secondary HPT (SHPT). Out of 168 articles identified, nine met inclusion criteria. Five reported both THPT and SHPT prevalences. Clinical trials that prescreened and excluded participants with HPT were excluded. Two studies included patients who received burosumab; the remainder involved conventional therapy or no treatment. The pooled prevalence of THPT across nine studies (583 patients) was 9.0% (95% CI 6.0 to 13%), while the pooled prevalence of SHPT across five studies (298 patients) was 34% (95% CI 18–54%). THPT prevalence did not differ by treatment type. Among studies reporting complications, nephrocalcinosis occurred in 29% (151/517) of patients, and parathyroidectomy was performed in 10% (27/275). Both tertiary and secondary HPT are common among patients with XLH. Although SHPT has historically received more attention, clinicians should be aware of the prevalence of THPT in XLH patients as well, and patients should be monitored carefully for hypercalcemia and other complications of HPT.