Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome.
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.


METHODS
Prospective, cross-sectional, single-centre study of patients with documented solid malignancies, hypercalcaemia and suppressed plasma PTH concentrations.


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.


CONCLUSIONS
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.
Schweitzer
D H
DH
Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands.
Hamdy
N A
NA
Frölich
M
M
Zwinderman
A H
AH
Papapoulos
S E
SE
D000368:Aged; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism; D002117:Calcitriol / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D044162:Parathyroid Hormone-Related Protein; D011446:Prospective Studies; D011506:Proteins / Q000032:analysis
C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D002117:Calcitriol