Hypophosphatemia in the Diagnosis and Management of Primary Hyperparathyroidism

Abstract

Background: Hypophosphatemia is a frequently underestimated metabolic disorder, yet it can be one of the first biochemical findings in primary hyperparathyroidism (PHPT). Current diagnostic and surgical criteria for PHPT do not include serum phosphate, despite its potential value as an early marker. Methods: We report the case of a 79-year-old woman with type 2 diabetes mellitus, hypertension and osteoarthritis, followed since 2015 for persistent hypophosphatemia (0.8 mg/dL) and stress fractures. Results: Initial calcium and vitamin D levels were normal, but PTH was elevated. Bone scintigraphy revealed multiple stress fractures, while ultrasound and sestamibi scan were inconclusive. Despite cholecalciferol and calcitriol supplementation, hypophosphatemia persisted. From 2023, progressive hypercalcemia developed (10.9 mg/dL), with sustained hypophosphatemia (1.7 mg/dL), persistently high PTH (121 pg/mL) and markedly elevated FGF-23 (1694 kRU/L). Renal phosphate wasting was demonstrated, with reduced tubular reabsorption. An 18F-fluorocholine PET-CT performed in 2024 identified two right parathyroid adenomas, establishing the diagnosis of PHPT. The patient was referred for parathyroidectomy. Conclusions: Hypophosphatemia may serve as a complementary biomarker in the diagnostic and therapeutic approach to PHPT, but only after other potential causes of low phosphate levels have been excluded, as illustrated in this case. Its consideration could facilitate the early identification of PHPT and improve clinical decision-making, particularly in patients who do not meet classical surgical indications.