Skip to main content

Advertisement

Log in

Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

Hypercalcemia is a frequent finding in cancer patients and can be observed in any type of cancer. The physician in charge of cancer patients often ignores non-malignant causes of hypercalcemia. Our objective was to review the causes of hypercalcemia in a large series of cancer patients.

Methods

We have retrospectively studied in a Cancer Centre all consecutive hypercalcemic (Ca> 10.5 mg/dl) patients over an 8-year period. Of 699 evaluated patients, 642 were analyzed after exclusion of patients whose hypercalcemia resolved after rehydration or who had a normal Ca level after correction for protein concentrations. Clinical information was gathered on the type of cancer, its histology, whether the disease was active or in complete remission, and on the presence of bone metastases. Biochemical data included serum Ca, Pi, proteins in all patients, PTH in most patients, and PTHrP, 25OH-Vitamin D, 1,25(OH)2–Vitamin D, TSH, and T4 in selected cases.

Results

By order of decreasing frequency, the main causes of hypercalcemia were cancer (69.0 %), primary hyperparathyroidism (24.6 %), hyperthyroidism (2.2 %), milk alkali syndrome (0.9 %), and sarcoidosis (0.45 %). In cancer-related causes, bone metastases accounted for 53.0 % of the cases, humoral hypercalcemia of malignancy (HHM) for 35.3 % while there were 11.7 % of cases apparently due to both HHM and bone metastases. Hypercalcemia was not due to cancer in 97 % (84/87) of the patients who were in complete remission. Even in patients with active neoplastic disease, the number of patients whose hypercalcemia was not due to cancer remained clinically relevant (115/555 = 20.5 %). In the 158 patients with primary hyperparathyroidism, 92 patients were in complete remission and 66 patients had active neoplastic disease.

Conclusions

In this large series of hypercalcemia in cancer patients, the cause was not due to cancer in almost one third of the cases. Most patients considered to be in complete remission had hypercalcemia due to a benign condition. In that perspective, serum PTH determination is essential in the approach of hypercalcemic cancer patients since primary hyperparathyroidism is by far the first non-malignant cause of hypercalcemia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Body JJ (2004) Hypercalcemia of malignancy. Semin Nephrol 24:48–54

    Article  PubMed  Google Scholar 

  2. Body JJ, Delmas PD (1992) Urinary pyridinium cross-links as markers of bone resorption in tumor-associated hypercalcemia. J Clin Endocrinol Metab 74:471–475

    Article  PubMed  CAS  Google Scholar 

  3. Toori KU, Bone MF, Labib MH (1999) Raised urinary pyridinium cross-links in humoral hypercalcaemia of malignancy. Ann Clin Biochem 36(Pt 1):107–108

    PubMed  Google Scholar 

  4. Grill V, Ho P, Body JJ, Johanson N, Lee SC, Kukreja SC, Moseley JM, Martin TJ (1991) Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab 73:1309–1315

    Article  PubMed  CAS  Google Scholar 

  5. Body JJ, Coleman R, Clezardin P, Ripamonti C, Rizzoli R, Aapro M (2007) International Society of Geriatric Oncology (SIOG) clinical practice recommendations for the use of bisphosphonates in elderly patients. Eur J Cancer 43:852–858

    Article  PubMed  CAS  Google Scholar 

  6. Santarpia L, Koch CA, Sarlis NJ (2010) Hypercalcemia in cancer patients: pathobiology and management. Horm Metab Res 42:153–164

    Article  PubMed  CAS  Google Scholar 

  7. Body JJ, Dumon JC, Thirion M, Cleeren A (1993) Circulating PTHrP concentrations in tumor-induced hypercalcemia: influence on the response to bisphosphonate and changes after therapy. J Bone Miner Res 8:701–706

    Article  PubMed  CAS  Google Scholar 

  8. Body JJ, Louviaux I, Dumon JC (2000) Decreased efficacy of bisphosphonates for recurrences of tumor-induced hypercalcemia. Support Care Cancer 8:398–404

    Article  PubMed  CAS  Google Scholar 

  9. Body JJ, Dumon JC (1994) Treatment of tumour-induced hypercalcaemia with the bisphosphonate pamidronate: dose–response relationship and influence of tumour type. Ann Oncol 5:359–363

    PubMed  CAS  Google Scholar 

  10. Kim SJ, Shiba E, Maeda I, Yoshioka T, Amino N, Noguchi S (2001) Screening for primary hyperparathyroidism (PHPT) in clinic patients: differential diagnosis between PHPT and malignancy-associated hypercalcemia by routine blood tests. Clin Chim Acta 305:35–40

    Article  PubMed  CAS  Google Scholar 

  11. Motellon JL, Javort Jimenez F, de Miguel F, Jaras MJ, Diaz A, Hurtado J, Esbrit P (2000) Parathyroid hormone-related protein, parathyroid hormone, and vitamin D in hypercalcemia of malignancy. Clin Chim Acta 290:189–197

    Article  PubMed  CAS  Google Scholar 

  12. Mundy GR, Cove DH, Fisken R (1980) Primary hyperparathyroidism: changes in the pattern of clinical presentation. Lancet 1:1317–1320

    Article  PubMed  CAS  Google Scholar 

  13. Walls J, Ratcliffe WA, Howell A, Bundred NJ (1994) Parathyroid hormone and parathyroid hormone-related protein in the investigation of hypercalcaemia in two hospital populations. Clin Endocrinol (Oxf) 41:407–413

    Article  CAS  Google Scholar 

  14. Jacobs TP, Bilezikian JP (2005) Clinical review: rare causes of hypercalcemia. J Clin Endocrinol Metab 90:6316–6322

    Article  PubMed  CAS  Google Scholar 

  15. Blomqvist CP (1986) Malignant hypercalcemia—a hospital survey. Acta Med Scand 220:455–463

    Article  PubMed  CAS  Google Scholar 

  16. Fisken RA, Heath DA, Bold AM (1980) Hypercalcaemia—a hospital survey. Q J Med 49:405–418

    PubMed  CAS  Google Scholar 

  17. Ling PJ, A’Hern RP, Hardy JR (1995) Analysis of survival following treatment of tumour-induced hypercalcaemia with intravenous pamidronate (APD). Br J Cancer 72:206–209

    Article  PubMed  CAS  Google Scholar 

  18. Nussbaum SR, Younger J, Vandepol CJ, Gagel RF, Zubler MA, Chapman R, Henderson IC, Mallette LE (1993) Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: comparison of 30-, 60-, and 90-mg dosages. Am J Med 95:297–304

    Article  PubMed  CAS  Google Scholar 

  19. Ralston SH, Fogelman I, Gardiner MD, Boyle IT (1984) Relative contribution of humoral and metastatic factors to the pathogenesis of hypercalcaemia in malignancy. Br Med J 288:1405–1408

    Article  CAS  Google Scholar 

  20. Rizzoli R, Thiebaud D, Bundred N, Pecherstorfer M, Herrmann Z, Huss HJ, Ruckert F, Manegold C, Tubiana-Hulin M, Steinhauer EU, Degardin M, Thurlimann B, Clemens MR, Eghbali H, Body JJ (1999) Serum parathyroid hormone-related protein levels and response to bisphosphonate treatment in hypercalcemia of malignancy. J Clin Endocrinol Metab 84:3545–3550

    Article  PubMed  CAS  Google Scholar 

  21. Endres DB, Villanueva R, Sharp CF Jr, Singer FR (1991) Immunochemiluminometric and immunoradiometric determinations of intact and total immunoreactive parathyrin: performance in the differential diagnosis of hypercalcemia and hypoparathyroidism. Clin Chem 37:162–168

    PubMed  CAS  Google Scholar 

  22. Body JJ, Dumon JC, Seraj F, Cleeren A (1992) Recovery of parathyroid hormone secretion during correction of tumor-associated hypercalcemia. J Clin Endocrinol Metab 74:1385–1388

    Article  PubMed  CAS  Google Scholar 

  23. Stewart AF (2005) Clinical practice. Hypercalcemia associated with cancer. N Engl J Med 352:373–379

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosures

no conflict of interest

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. J. Body.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soyfoo, M.S., Brenner, K., Paesmans, M. et al. Non-malignant causes of hypercalcemia in cancer patients: a frequent and neglected occurrence. Support Care Cancer 21, 1415–1419 (2013). https://doi.org/10.1007/s00520-012-1683-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-012-1683-5

Keywords

Navigation