Recurrent pathological fractures in chronic kidney disease revealing overlapping neglected primary hyperparathyroidism and GDF5-associated skeletal dysplasia.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by the excessive secretion of parathyroid hormone (PTH), resulting in significant hypercalcemia and skeletal complications. In the context of chronic kidney disease (CKD), neglected PHPT can progress to a biochemical profile resembling tertiary hyperparathyroidism (THPT), further complicating diagnosis, especially when concomitant genetic skeletal disorders (GSD) exist.

CASE REPORT: We present a rare and complex case of a 63-year-old woman with stage 3 CKD who presented with recurrent pathological fractures, severe hypercalcemia, and extensive osteolytic bone lesions in both femurs. The patient's clinical picture was complicated by notable skeletal anomalies, including short stature, brachydactyly, and hypoplastic metatarsals. Elevated serum calcium, markedly increased PTH levels, hypercalciuria, hyperphosphaturia, and parathyroid imaging, confirmed previously untreated PHPT resulting in a THPT-like biochemical profile in the setting of CKD. The patient ultimately underwent surgical fixation for bilateral lower limb fractures, followed by a simple parathyroidectomy, achieving symptomatic relief and metabolic stabilization. A genetic investigation, prompted by distinctive skeletal features, uncovered a frameshift mutation in the growth differentiation factor 5 (GDF5) gene indicative of brachydactyly type C, a rare form of GSD.

CONCLUSION: This case highlights the complexity in differentiating PHPT from other causes of hyperparathyroidism in the setting of CKD, particularly when concurrent skeletal dysplasia is present. The thorough clinical, biochemical, imaging, and genetic assessments were pivotal in reaching an accurate diagnosis and guiding appropriate surgical management.