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A case of resistant hypercalcemia of malignancy with a proposed treatment algorithm.
Ann Pharmacother. 2009 Sep; 43(9):1532-8.AP

Abstract

OBJECTIVE

To report and describe a case of refractory hypercalcemia of malignancy (HCM) associated with metastatic, transitional-cell carcinoma of the left ureter.

CASE SUMMARY

A 71-year-old male complaining of generalized weakness and night sweats for the past 3 months was sent to the emergency department when routine laboratory tests revealed a corrected serum calcium concentration of 14.4 mg/dL. Intravenous crystalloid fluids and pamidronate were administered with achievement of normocalcemia, and the patient was discharged. Computed tomography scan and liver biopsy revealed recurrent transitional-cell carcinoma with extensive liver metastasis. The patient returned approximately 1 week after discharge with a serum calcium level of 13.9 mg/dL. An initial decrease in serum calcium was observed with intravenous fluids, pamidronate, and calcitonin, but the normalization slowed and reversed within 3 days. Normocalcemia was achieved upon administration of zoledronic acid and the patient was discharged on day 14. The patient died 1 week after discharge from complications unrelated to hypercalcemia.

DISCUSSION

Hypercalcemia is common in patients with malignancy and is associated with potentially life-threatening sequelae. Four mechanisms of HCM have been recognized thus far, with ectopic tumor production of parathyroid hormone-related protein (PTHrP) being the leading cause. Treatment of HCM revolves around 2 principles: treatment of the underlying malignancy along with reduction of the serum calcium level. Evidence-based therapies for management include: intravenous crystalloid fluids with or without loop diuretics, bisphosphonates, calcitonin, gallium nitrate, and corticosteroids. Therapies used for this patient included aggressive hydration, calcitonin, and 3 distinct treatment courses of intravenous bisphosphonates with varying success. Other potential agents were explored for use in the event of continued hypercalcemia. These therapies remain viable options based on individual patient factors. To our knowledge, no published guidelines or algorithms exist for choosing between additional modalities in the treatment of refractory HCM.

CONCLUSIONS

For patients with HCM who do not achieve a response from bisphosphonates, or for those who need repeated dosing more often than expected, changing to a different drug class could be an alternative. The specific mechanism of hypercalcemia should be considered when developing a treatment regimen for patients who have had a suboptimal response to initial therapy with bisphosphonates. Multiple treatment modalities exist for the treatment of hypercalcemia, each with a different mechanism of action. As with the treatment of other disease states, we can use this knowledge to more specifically target the mechanism of the patient's disease.

Links

Publisher Full Text

Authors+Show Affiliations

McMahan J
John Cochran Veterans Affairs Medical Center, St. Louis, MO, USA.
Linneman T
No affiliation info available

MeSH

AgedAlgorithmsBone Density Conservation AgentsCalcitoninCarcinoma, Transitional CellCrystalloid SolutionsDiphosphonatesHumansHypercalcemiaImidazolesIsotonic SolutionsMaleNeoplasm MetastasisPamidronateUreteral NeoplasmsZoledronic Acid

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

19622757

Citation

McMahan, Jonathan, and Travis Linneman. "A Case of Resistant Hypercalcemia of Malignancy With a Proposed Treatment Algorithm." The Annals of Pharmacotherapy, vol. 43, no. 9, 2009, pp. 1532-8.
McMahan J, Linneman T. A case of resistant hypercalcemia of malignancy with a proposed treatment algorithm. Ann Pharmacother. 2009;43(9):1532-8.
McMahan, J., & Linneman, T. (2009). A case of resistant hypercalcemia of malignancy with a proposed treatment algorithm. The Annals of Pharmacotherapy, 43(9), 1532-8. https://doi.org/10.1345/aph.1L313
McMahan J, Linneman T. A Case of Resistant Hypercalcemia of Malignancy With a Proposed Treatment Algorithm. Ann Pharmacother. 2009;43(9):1532-8. PubMed PMID: 19622757.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A case of resistant hypercalcemia of malignancy with a proposed treatment algorithm. AU - McMahan,Jonathan, AU - Linneman,Travis, Y1 - 2009/07/21/ PY - 2009/7/23/entrez PY - 2009/7/23/pubmed PY - 2009/11/3/medline SP - 1532 EP - 8 JF - The Annals of pharmacotherapy JO - Ann Pharmacother VL - 43 IS - 9 N2 - OBJECTIVE: To report and describe a case of refractory hypercalcemia of malignancy (HCM) associated with metastatic, transitional-cell carcinoma of the left ureter. CASE SUMMARY: A 71-year-old male complaining of generalized weakness and night sweats for the past 3 months was sent to the emergency department when routine laboratory tests revealed a corrected serum calcium concentration of 14.4 mg/dL. Intravenous crystalloid fluids and pamidronate were administered with achievement of normocalcemia, and the patient was discharged. Computed tomography scan and liver biopsy revealed recurrent transitional-cell carcinoma with extensive liver metastasis. The patient returned approximately 1 week after discharge with a serum calcium level of 13.9 mg/dL. An initial decrease in serum calcium was observed with intravenous fluids, pamidronate, and calcitonin, but the normalization slowed and reversed within 3 days. Normocalcemia was achieved upon administration of zoledronic acid and the patient was discharged on day 14. The patient died 1 week after discharge from complications unrelated to hypercalcemia. DISCUSSION: Hypercalcemia is common in patients with malignancy and is associated with potentially life-threatening sequelae. Four mechanisms of HCM have been recognized thus far, with ectopic tumor production of parathyroid hormone-related protein (PTHrP) being the leading cause. Treatment of HCM revolves around 2 principles: treatment of the underlying malignancy along with reduction of the serum calcium level. Evidence-based therapies for management include: intravenous crystalloid fluids with or without loop diuretics, bisphosphonates, calcitonin, gallium nitrate, and corticosteroids. Therapies used for this patient included aggressive hydration, calcitonin, and 3 distinct treatment courses of intravenous bisphosphonates with varying success. Other potential agents were explored for use in the event of continued hypercalcemia. These therapies remain viable options based on individual patient factors. To our knowledge, no published guidelines or algorithms exist for choosing between additional modalities in the treatment of refractory HCM. CONCLUSIONS: For patients with HCM who do not achieve a response from bisphosphonates, or for those who need repeated dosing more often than expected, changing to a different drug class could be an alternative. The specific mechanism of hypercalcemia should be considered when developing a treatment regimen for patients who have had a suboptimal response to initial therapy with bisphosphonates. Multiple treatment modalities exist for the treatment of hypercalcemia, each with a different mechanism of action. As with the treatment of other disease states, we can use this knowledge to more specifically target the mechanism of the patient's disease. SN - 1542-6270 UR - https://www.unboundmedicine.com/medline/citation/19622757/A_case_of_resistant_hypercalcemia_of_malignancy_with_a_proposed_treatment_algorithm_ L2 - https://journals.sagepub.com/doi/10.1345/aph.1L313?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -