Endocrine Abstracts

Fibroblast growth factor 23 (FGF-23) is a phosphatonin produced by osteocytes in response to serum phosphate concentration. Immunoassays are widely employed to detect C-terminal fragments of FGF-23 (cFGF-23). Quantitative assays for intact FGF-23 (iFGF-23) measurement are also available. Causes of increased FGF-23 include Tumour Induced Osteomalacia (TIO), X-linked hypophosphataemic rickets (XLH) and end stage renal disease (ESRD). We observed that some individuals, with no identifiable classical cause of elevated FGF-23, have elevated cFGF-23 and normal iFGF-23. 561 individuals, with elevated cFGF-23 and normal iFGF-23, were identified from a metabolic bone clinic at our centre. 361 patients were included in our final analysis and were further characterised using their bone-metabolic biochemical parameters and clinical data. Patients with a confirmed diagnosis of TIO, XLH, hypophosphataemia (PO₄ <0.8 mmol/l) and ESRD on renal replacement therapy were excluded. Each patient’s primary clinical diagnosis was correlated with their biochemical results. In the final cohort, the mean cFGF-23 was 224RU/mL (RR <100RU/mL, range 100 – 6720); mean iFGF-23, 63pg/mL (RR 33 – 110pg/mL, range 0 – 109); mean PTH, 8.0 pmol/l (RR 1.6 – 6.9pmol/l); mean eGFR, 69 ml/min/1.73m² (range 20 – 90); mean 25-OH vitamin D 68.9 nmol/l; mean albumin adjusted calcium 2.6 mmol/l (RR 2.2 – 2.6 mmol/l); and inorganic phosphate 1.0 mmol/l (RR 0.8 – 1.5). As expected, negative correlations between eGFR and C-terminal and iFGF-23 concentrations were observed (r² value -0.035 and -0.121 respectively). The major associated co-morbidities in the cohort were osteoporosis on treatment (n = 63), primary hyperparathyroidism (PHPT) (n = 90) and vitamin D deficiency (n = 90). A significant proportion of cases with elevated cFGF-23 have normal iFGF-23 measurements. The commonest causes of this biochemical picture in our cohort were PHPT, osteoporosis on treatment, and vitamin D deficiency. Thus, it appears that cFGF-23 assays may be more susceptible to confounding by non-classical causes of FGF-23 elevation than iFGF-23 assays.