Endocrine Abstracts

Intact PTH [PTH(1–84)] measurements separate hypercalcaemic patients into 1) a parathyroid cause (usually 1°HPT) from 2) non-parathyroid causes (usually hypercalcaemia of malignancy). Improved sensitivity increases confidence in diagnosing hypoparathyroidism. PTH RIAs had problems with C-terminal PTH fragments and in renal failure circulating PTH (35–84) persists for hours giving high RIA PTH. Intact PTH is retained in renal failure and this resulted in new approaches to 2°HPT and renal osteodystrophy. Although discrepancies exist between intact PTH and the severity of bone disease in renal failure and low intact PTH can result in adynamic bone disease, these problems can be overcome by maintaining intact PTH 2–3 times the ULN. HPLC of CRF samples identified circulating PTH fragments including PTH (7-84). PTH (7-84) blocks PTH (1–84 and 1–34) activity. PTH (7–84) was detected by all early intact PTH assays and contributed to the intact PTH value. This lead to assays measuring only PTH (1–84) termed “whole molecule” PTH assays. Subtracting whole molecule PTH from intact PTH estimates PTH (7–84). Some authors suggest this can help identify adynamic bone disease. Others argue the relative percentage of PTH (7–84) remains constant and there is no advantage measuring whole PTH. In 1° HPT the majority of patients have elevated whole PTH.

FGF 23 is important in phosphate (PO₄) and vitamin D metabolism. It increases following a PO₄ load and produces urinary PO₄ excretion. FGF 23 decreases 1,25 vitamin D production. When FGF 23 is increased there is a classical picture of hypophosphataemia, phosphaturia and inappropriate 1,25 vitamin D. Assays exist measuring the intact FGF 23 (1–251) and various C terminal fragments. High FGF 23 is found in oncogenic osteomalacia and normalises with tumour excision. FGF 23 is increased in X-linked hypophosphataemia (XLH) due to inactivating mutations of the PHEX gene and in autosomal dominant hypophosphataemic rickets (ADHR) where a mis-sense mutation results in FGF 23 resistant to protease metabolism. Osteogenic cells in patients with Fibrous Dysplasia (FD) can over produce FGF 23.

Recent reports highlight the differences in FGF 23 concentrations observed in hypophosphataemic patients depending on the assay used and there are differences in the ability to differentiate disease states using the intact and C terminal assays.