OBJECTIVE: Parathyroid hormone-related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia. DESIGN: Prospective, cross-sectional, single-centre study of patients with documented solid malignancies, hypercalcaemia and suppressed plasma PTH concentrations. PATIENTS AND METHODS: Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N-cAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid malignancies and hypercalcaemia and bone scans were performed. RESULTS: In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25-(OH)2D concentrations were not appropriately suppressed (> 92 pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1.6 pmol/l) had lower serum 1,25-(OH)2D concentrations than those with elevated levels (> 1.6 pmol/l) (47 +/- 6 vs 70 +/- 7 pmol/l, respectively; P < 0.04). Serum 1,25-(OH)2D concentrations were higher in patients with negative bone scans than in those with metastatic bone disease (80 +/- 9 vs 50 +/- 5 pmol/l; P < 0.01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25-(OH)2D (r = 0.51; P < 0.03) whereas there was no such correlation in those with a positive scan. CONCLUSION: Contrary to current belief, serum 1,25-(OH)2D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further insights into the pathophysiology of malignancy-associated hypercalcaemia and may help in the clinical management of these patients.
OBJECTIVE:Parathyroid hormone-related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia. DESIGN: Prospective, cross-sectional, single-centre study of patients with documented solid malignancies, hypercalcaemia and suppressed plasma PTH concentrations. PATIENTS AND METHODS: Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N-cAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid malignancies and hypercalcaemia and bone scans were performed. RESULTS: In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25-(OH)2D concentrations were not appropriately suppressed (> 92 pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1.6 pmol/l) had lower serum 1,25-(OH)2D concentrations than those with elevated levels (> 1.6 pmol/l) (47 +/- 6 vs 70 +/- 7 pmol/l, respectively; P < 0.04). Serum 1,25-(OH)2D concentrations were higher in patients with negative bone scans than in those with metastatic bone disease (80 +/- 9 vs 50 +/- 5 pmol/l; P < 0.01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25-(OH)2D (r = 0.51; P < 0.03) whereas there was no such correlation in those with a positive scan. CONCLUSION: Contrary to current belief, serum 1,25-(OH)2D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further insights into the pathophysiology of malignancy-associated hypercalcaemia and may help in the clinical management of these patients.
Authors: H J Zeimer; T M Greenaway; J Slavin; D K Hards; H Zhou; J C Doery; A N Hunter; A Duffield; T J Martin; V Grill Journal: Am J Pathol Date: 1998-01 Impact factor: 4.307