Clinical Practice Guideline

Hypercalcemia Guideline Resources

November 09, 2022

December XX, 2022

Full Guideline: Treatment of Hypercalcemia of Malignancy in Adults: An Endocrine Society Clinical Practice Guideline
JCEM | March 2023 (online December 2022)

Ghada El-Hajj Fuleihan (Chair),  Gregory A. Clines, Mimi I. Hu,  Claudio Marcocci, M. Hassan Murad, Thomas Piggott,  Catherine Van Poznak, Joy Y. Wu, Matthew T. Drake (Co-Chair)

The 2022 guideline on management of hypercalcemia of malignancy:

  • Focuses on the treatment of adults with hypercalcemia of malignancy
  • Emphasizes the use of controlling hypercalcemia and preventing its recurrence

A systematic review supporting the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults [LINK COMING; PLEASE LINK THIS WHOLE TITLE]

Patient and Physician Decisional Factors Regarding Hypercalcemia of Malignancy Treatment: A Novel Mixed-Methods Study [LINK COMING; PLEASE LINK THIS WHOLE TITLE]


Resources

  • Clinician Education Presentation (Free CME) | Endocrine Society
  • Patient Resources | ENDOCares BROKEN LINK
  • Guidelines Pocket Card | Guideline Central BROKEN LINK
  • Interview with the Chairs Endocrine News LINK COMING

Essential Points

  • Hypercalcemia of malignancy (HCM), a condition associated with high morbidity and mortality, is the most common metabolic complication of malignancies.
  • All adults with HCM should receive treatment with denosumab (Dmab) or an intravenous (IV) bisphosphonate (BP).
  • Adults with calcitriol-mediated HCM should first be treated with glucocorticoids, with the addition of Dmab or an IV BP if glucocorticoid therapy is insufficient.

List of Recommendations


Adults with hypercalcemia of malignancy

Question 1. Should a bisphosphonate or denosumab versus no treatment with a bisphosphonate or denosumab be used for adults with hypercalcemia of malignancy?

 

Recommendation 1: In adults with hypercalcemia of malignancy (HCM), we recommend treatment with an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) compared with management without an IV BP or Dmab. (1⊕◯◯◯)

 

Question 2. Should denosumab versus a bisphosphonate be used for adults with hypercalcemia of malignancy?


Recommendation 2:
In adults with hypercalcemia of malignancy (HCM), we suggest treatment with denosumab (Dmab) over an intravenous (IV) bisphosphonate (BP). (2⊕◯◯◯)

 

Question 3. Should addition of calcitonin versus no calcitonin be used for adults with hypercalcemia of malignancy who will be started on a bisphosphonate or denosumab?


Recommendation 3:
In adults with severe hypercalcemia of malignancy (HCM) (serum calcium [SCa]>14 mg/dL [3.5 mmol/L]), we suggest a combination of calcitonin and an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) as initial treatment, compared with only IV BP or Dmab. (2⊕◯◯◯)

Remark:

  • Calcitonin treatment should be limited to 48-72 hours due to tachyphylaxis.

Refractory and recurrent hypercalcemia

Question 4. Should denosumab versus no denosumab be used in adults with refractory/recurrent hypercalcemia of malignancy on a bisphosphonate?


Recommendation 4:
In adults with refractory/recurrent hypercalcemia of malignancy (HCM) on an intravenous (IV) bisphosphonate (BP), we suggest the use of denosumab (Dmab), compared with management without Dmab. (2⊕◯◯◯)

 

Hypercalcemia due to calcitriol-associated malignancy

Question 5. Should a bisphosphonate or denosumab versus no bisphosphonate or denosumab be used for adults with hypercalcemia resulting from tumors associated with high calcitriol levels who are already treated with a glucocorticoid?


Recommendation 5:
In adults with hypercalcemia of malignancy (HCM) from tumors associated with high calcitriol levels, such as lymphomas, who are already receiving glucocorticoid therapy but who continue to have severe or symptomatic hypercalcemia, we suggest the addition of an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) compared with management without an IV BP or Dmab. (2⊕◯◯◯)

 

Adults with hypercalcemia due to parathyroid carcinoma

Question 6. Should a calcimimetic versus a bisphosphonate or denosumab be used for adults with hypercalcemia due to parathyroid carcinoma?


Recommendation 6: In adult patients with hypercalcemia
of malignancy (HCM) due to parathyroid carcinoma, we suggest treatment with either a calcimimetic or an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab). (2⊕◯◯◯)

Remarks:

  • In adult patients with parathyroid carcinoma, surgery should be considered when feasible, once control of severe hypercalcemia has been achieved; however, surgical considerations were outside of the scope of this guideline.
  • Depending on the clinical situation and severity of hypercalcemia, an IV BP or Dmab may be useful prior to calcimimetic initiation. In adults with mild hypercalcemia and related symptoms, we suggest starting therapy with calcimimetics; conversely adults with moderate-to severe hypercalcemia and related symptoms, an IV BP or Dmab should be the initial therapy.
  • This recommendation considers the more rapid onset of action of an IV BP or Dmab, and generally better tolerability profile, as compared to a calcimimetic (as adverse events are common with increasing calcimimetic doses).

Question 7. Should addition of a bisphosphonate or denosumab versus no addition of a bisphosphonate or denosumab be used for adults with hypercalcemia due to parathyroid carcinoma in patients not adequately controlled with a calcimimetic?


Recommendation 7:
In adult patients with hypercalcemia of malignancy (HCM) due to parathyroid carcinoma not adequately controlled despite treatment with a calcimimetic, we suggest the addition of an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) compared with management without an IV BP or Dmab. (2OOO)

 

Question 8. Should a calcimimetic versus no calcimimetic be used for adults with hypercalcemia due to parathyroid carcinoma who are not adequately controlled with a bisphosphonate or denosumab?


Recommendation 8: In adult patients with hypercalcemia of malignancy (HCM) due to parathyroid carcinoma who are not adequately controlled on an intravenous (IV) bisphosphonate (BP) or denosumab (Dmab) therapy, we suggest the addition of a calcimimetic compared with management without a calcimimetic. (2⊕
OOO)

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