Abstract / Summary
Primary hyperparathyroidism (PHPT) is definitively treated by parathyroidectomy (PTx), with surgical cure conventionally defined by sustained normocalcemia. However, some patients develop elevated parathyroid hormone (PTH) concentrations despite normal postoperative calcium levels. This heterogeneous condition may reflect vitamin D insufficiency, reduced calcium availability, skeletal remineralization, or renal dysfunction, but may occasionally indicate persistent parathyroid autonomy or precede biochemical recurrence. Fibroblast growth factor 23 (FGF23), an osteocyte-derived regulator of phosphate excretion and calcitriol synthesis, occupies a central position within the bone–kidney–parathyroid axis and may participate in metabolic adaptation after PTx. This narrative review examines FGF23 regulation, circulating concentrations, clinical associations, and perioperative dynamics in PHPT. A structured search of PubMed/MEDLINE, Scopus, and Web of Science identified 11 original clinical studies directly evaluating FGF23 in PHPT. Findings were discordant: some studies reported increased preoperative concentrations and a postoperative decline, whereas others found normal levels or no significant change after surgery. Differences in disease phenotype, renal function, vitamin D status, assay methodology, supplementation, and sampling time may partly explain this heterogeneity. Notably, no study related perioperative FGF23 changes to subsequent PTH trajectories, and studies of postoperative eucalcemic PTH elevation did not measure FGF23. FGF23 cannot currently be considered a diagnostic or prognostic biomarker in PHPT. Nevertheless, serial assessment alongside conventional mineral-metabolism parameters may clarify endocrine adaptation after PTx and determine whether biologically distinct postoperative phenotypes exist.