SUN-526 Prevalence of Hyperparathyroidism in X-Linked Hypophosphatemia

Abstract

X-linked hypophosphatemia, due to PHEX mutations results in elevated fibroblast growth factor 23, hypophosphatemia and rickets/osteomalacia. Conventional therapy requires high doses of phosphate salts combined with active vitamin D analogues. Known complications of this regimen include nephrocalcinosis and secondary and tertiary hyperparathyroidism. The prevalence of hyperparathyroidism and treatment with parathyroidectomy in XLH is uncertain. The goal of this study was to estimate the prevalence of hyperparathyroidism and parathyroidectomy among XLH patients. We also characterized the outcome of parathyroidectomy for XLH patients. We conducted a retrospective chart review study from 1/1/2010 to 12/31/2017 using data from electronic records and paper charts. All XLH patients attending our center were eligible for analysis if they had at least one concurrent measurement of parathyroid hormone (PTH) and serum calcium. Categorization was based on the highest PTH and calcium values, persistence of hypercalcemia and a history of parathyroidectomy. Of the 104 patients having a diagnosis of XLH, 84 had concurrent measurements available of calcium and PTH. Data were available from 46 patients as adults and 43 as children (5 as both). Of these, 71/84 (84.52%), had evidence of secondary or tertiary hyperparathyroidism at any time point. Secondary hyperparathyroidism (defined as any PTH value ≥65pg/mL and not hypercalcemic) occurred in 35/43 (81.4%) children and 41/46 (89.1%) adults at any time point. Resolution of secondary hyperparathyroidism was observed in all children, except two with parathyroidectomies at ages 15 and 18 for tertiary hyperparathyroidism. Resolution of secondary hyperparathyroidism was observed in 27/41 adults. Tertiary (or hypercalcemic) hyperparathyroidism had an overall prevalence of 14/84 (16.67%) patients or 14/46 (30.4%) of adults (n=10 with PTH ≥65 pg/mL plus Calcium ≥10.5 mg/dl; n=1 with PTH ≥65 pg/mL plus Calcium 10.2-10.4 mg/dl; n=2 with PTH ≥50 pg/mL plus Calcium ≥10.5 mg/dL; n=1 with parathyroidectomy prior to presentation to our center). Parathyroidectomy was documented in 8/84 (9.5%) of the total population, or 8/46 (17.4%) of adults with XLH. After parathyroidectomy, residual or recurrent tertiary hyperparathyroidism was detected in 6/8 patients at a median of 6 years (ranging from 0 to 29 years). One patient had chronic postoperative hypoparathyroidism, and one patient remains normocalcemic 4 years after surgery. The majority of patients with XLH develop hyperparathyroidism during treatment with phosphate and active vitamin D. A significant proportion develop hypercalcemic hyperparathyroidism and most had recurrence of parathyroid autonomy after surgery. Careful monitoring and dose adjustment to minimize elevations of PTH are recommended.