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

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 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: D H Schweitzer, N A Hamdy, M Frölich, A H Zwinderman, S E Papapoulos
• Journal: Clinical endocrinology (Clin Endocrinol (Oxf)) Vol. 41 Issue 2 Pg. 251-6 (Aug 1994) ISSN: 0300-0664 [Print] England
• PMID: 7923831 (Publication Type: Comparative Study, Journal Article)

Chemical References

• PTHLH protein, human
• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• Proteins
• Calcitriol

Topics

• Aged
• Bone Neoplasms (secondary)
• Breast Neoplasms (metabolism)
• Calcitriol (metabolism)
• Cross-Sectional Studies
• Female
• Humans
• Hypercalcemia (etiology, metabolism)
• Male
• Middle Aged
• Neoplasms (complications, metabolism)
• Parathyroid Hormone (blood)
• Parathyroid Hormone-Related Protein
• Prospective Studies
• Proteins (analysis)