Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome |
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| Authors: | Dave H Schweitzer Neveen A T Hamdy Marijke Frölich Aellko H Zwinderman Socrates E Papapoulos |
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| Institution: | Clinical Investigation Unit Department of Endocrinology and Metabolic Diseases;Department of Clinical Chemistry, University Hospital, Leiden;Department of Medical Statistics, University of Leiden, The Netherlands |
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| Abstract: | 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 malignancles, 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 mallgnancles 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 (>92pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1·6 pmol/l) had lower serum 1,25-(OH)2,D 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)2,D (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. |
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