Endocrine Abstracts

Background: X-linked hypophosphatemia (XLH) is a rare hereditary disorder characterised by defective bone and dental mineralisation causing rickets impaired growth, nephrocalcinosis and hyperparathyroidism. It is driven by elevated fibroblast growth factor 23 (FGF23) and consequent hypophosphatemia. Standard management typically involves high doses of oral phosphate salts and active vitamin D analogues. New therapeutic options are emerging, such as Burosumab which is a monoclonal antibody that blocks fibroblast growth factor 23 (FGF23), which leads to increased renal phosphate reabsorption, and increased serum phosphate and 1,25-dihydroxyvitamin D (calcitriol) levels, improving bone mineralisation and quality of life.

Case Report: We describe an unusual case of a 44 year-old man with XLH complicated by tertiary hyperparathyroidism (TH), despite ongoing phosphate and vitamin D replacement. While secondary hyperparathyroidism is a recognised treatment-related complication, progression to irreversible TH is rarely reported. In 2019, he developed hyperparathyroidism and parathyroid imaging (MIBI scan and 4 D CT) demonstrated diffuse parathyroid hyperplasia. He underwent a total parathyroidectomy, which initially normalised calcium levels. Histology confirmed hyperplasia of all four glands. However, in 2022, the patient again developed progressive hypercalcemia and elevated parathyroid hormone (PTH) levels, despite normal phosphate and Vitamin D levels. Repeat MIBI scanning revealed a 12 mm hyperplastic parathyroid nodule in the soft tissues of the neck. Current management considerations include surgical re-exploration, combined with Burosumab and cinacalcet (a calcimimetic) to prevent further recurrence.

Conclusion: This case highlights the challenges of managing refractory tertiary hyperparathyroidism in XLH and the need for alternative therapeutic strategies. Further research is required to establish whether surgical intervention or targeted medical therapy—such as Burosumab, with or without calcimimetics—should be prioritised in this complex clinical setting.

Keywords: Burosumab, calcitriol, fibroblast growth factor 23, hypophosphatemia, tertiary hyperparathyroidism, X-linked hypophosphatemic rickets