ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P492 | DOI: 10.1530/endoabs.63.P492

Hyperparathyroidism in patients with X-linked hypophosphatemia

Anne-Lise Lecoq1, Philippe Chaumet-Riffaud2, Anne Blanchard3, Anya Rothenbuhler4, Benoit Lambert5, Alexandrine Bay6, Caroline Silve7, Marie Piketty8, Philippe Chanson1,9, Sylvie Brailly-Tabard10, Agnès Linglart4 & Peter Kamenicky1,9,11


1AP-HP, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre, France; 2Collège de l’Autorité de sûreté nucléaire, Montrouge, France; 3AP-HP, Hôpital Européen Georges Pompidou, Centre d’Investigation Clinique 1418, Paris, France; 4AP-HP, Hôpital Bicêtre, Service d’Endocrinologie Pédiatrique, Centre de références des maladies rares du Calcium et du Phosphore, Le Kremlin Bicêtre, France; 5AP-HP, Hôpital Bicêtre, Service de Chirurgie viscérale et digestive, Le Kremlin Bicêtre, France; 6AP-HP, Hôpital Bicêtre, Service d’Anatomie et Cytologie Pathologiques, Le Kremlin Bicêtre, France; 7AP-HP, Hôpital Cochin, Service de génétique et biologie moléculaires, Paris, France; 8AP-HP, Hôpital Necker, Service d’Explorations fonctionnelles Physiologie et Neurophysiologie, Paris, France; 9Univ Paris Saclay-Paris Sud, Le Kremlin Bicêtre, France; 10AP-HP, Hôpital Bicêtre, Laboratoire de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin Bicêtre, France; 11Unité INSERM 1185, Le Kremlin Bicêtre, France.


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 1.03–1.21, P<0.0001). Calcemia was similar in both groups. Patients had higher PTH levels compared to healthy controls (53.5 ng/l, IQR 36.7–72.7 vs 36 ng/l, IQR 27.7–44, 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 30–53) 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 2.15–2.27 vs 2.55 mmol/l, IQR 2.50–2.60) and phosphate concentrations increased (0.54 mmol/l, IQR 0.46–0.64 vs 0.47 mmol/l, 0.42–0.51).

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.