Tertiary hyperparathyroidism in two paediatric patients with X-linked hypophosphatemia during Burosumab treatment

Introduction: Although secondary hyperparathyroidism is known in X-linked hypophosphatemia (XLH) patients receiving treatment, tertiary hyperparathyroidism with hypercalcemia is rare, especially in children. We report two paediatric XLH patients treated with Burosumab who developed this rare complication.

Case descriptions: 1: A female patient with XLH on conventional therapy (phosphate and active vitamin D) since one year of age was switched to Burosumab at 10 years. At 14 years of age, she developed tertiary hyperparathyroidism with hypercalcaemia. Burosumab was continued. Post-parathyroidectomy her hypercalcaemia resolved and 4 years post-surgery her calcium levels continue to remain normal. 2: A female patient with XLH on conventional therapy since 4 months of age was switched to Burosumab at 4 years of age. At 7 years of age, she developed secondary hyperparathyroidism and within 6 months she developed tertiary hyperparathyroidism. Burosumab was discontinued at 7.5 years of age, and she was commenced on Cinacalcet but, hypercalcaemia failed to resolve. Post-parathyroidectomy her tertiary hyperparathyroidism resolved. However, within 2 weeks, PTH increased which normalised with Cinacalcet. Burosumab has been recommenced and she continues cinacalcet.

Discussion: The cause of tertiary hyperparathyroidism is not clear in these patients. Higher post-dose phosphate levels or a direct effect of PHEX mutation on the parathyroid gland could have triggered PTH secretion.

Conclusion: XLH patients treated with Burosumab can develop hyperparathyroidism and should be regularly monitored for the development of secondary and tertiary hyperparathyroidism.