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Medline ® Abstract for Reference 20

of 'Hypercalcemia of malignancy: Mechanisms'

Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome.
Schweitzer DH, Hamdy NA, Frölich M, Zwinderman AH, Papapoulos SE
Clin Endocrinol (Oxf). 1994;41(2):251.
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 withplasma 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.
Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands.