Background: X-linked hypophosphatemia (XLH) is a rachitic disorder characterized by renal tubular phosphate wasting resulting from increased circulating activity of the fibroblast growth factor FGF23. Secondary and tertiary hyperparathyroidism have been reported in XLH patients in small retrospective studies, however this complication has never been systematically evaluated in a large cohort.
Aim of the study: To compare parathyroid function of adult XLH patients with healthy subjects and to describe the prevalence and clinical presentation of hyperparathyroidism.
Methods: We conducted a prospective observational case-control study (CNIL 2171036 v 0) in a single tertiary referral center. Each XLH patients was compared to two healthy volunteers matched for sex, age and plasma 25-OH vitamin D concentrations. Healthy volunteers were selected among participants of the VARIETE trial (NCT01831648). Univariable linear regression analysis was performed to define parameters influencing PTH concentrations in this population. Data are expressed as median and interquartile range (IQR).
Results: 68 patients (51 women and 17 men) were recruited and matched with 136 healthy volunteers. Phosphatemia was significantly lower in XLH patients than in healthy controls (0.57 mmol/l, IQR 0.50-0.64 vs 1.11 mmol/l, IQR 1.031.21, P<0.0001). Calcemia was similar in both groups. Patients had higher PTH levels compared to healthy controls (53.5 ng/l, IQR 36.772.7 vs 36 ng/l, IQR 27.744, P<0.0001). Seventeen out of the 68 (25%) patients had a PTH concentration above the upper limit of the normal range. FGF23 concentrations were higher in patients than in controls (P<0.0001), whereas 1,25(OH)2D concentrations were comparable. In patients, linear regression analysis showed an unexpected positive relationship between PTH and serum calcium concentrations (R2=0.1238, P=0.0033) and a negative relationship between PTH and serum phosphate concentrations (R2=0.0575, P=0.0489). Eight of the 68 (12%) patients (40 years, IQR 3053) presented with autonomous hypercalcemic hyperparathyroidism, associated with nephrocalcinosis in two patients and osteoporosis in two patients. All underwent surgery with cervical exploration; four presented with a single parathyroid adenoma and four with hyperplasia. After parathyroidectomy, serum calcium concentrations decreased (2.20 mmol/l, IQR 2.152.27 vs 2.55 mmol/l, IQR 2.502.60) and phosphate concentrations increased (0.54 mmol/l, IQR 0.460.64 vs 0.47 mmol/l, 0.420.51).
Conclusion: Secondary hyperparathyroidism with disrupted physiological regulation of parathyroid function is frequent in adult XLH patients. Young-onset hypercalcemic hyperparathyroidism, resulting from parathyroid adenomas or hyperplasia, worsens hypophosphatemia and leads to renal and skeletal complications.
18 - 21 May 2019
European Society of Endocrinology