What are the serum calcium levels for grade 1, 2, 3, and 4 hypercalcemia according to the Common Terminology Criteria for Adverse Events (CTCAE)?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 24, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Research

According to the Common Terminology Criteria for Adverse Events (CTCAE), hypercalcemia is graded on a scale from 1 to 4 based on serum calcium levels and clinical symptoms, with Grade 1 defined as calcium levels above the upper limit of normal (ULN) up to 11.5 mg/dL (2.9 mmol/L), Grade 2 ranging from >11.5 mg/dL to 12.5 mg/dL (>2.9 to 3.1 mmol/L), Grade 3 defined as calcium levels >12.5 mg/dL to 13.5 mg/dL (>3.1 to 3.4 mmol/L), and Grade 4 being life-threatening with calcium levels >13.5 mg/dL (>3.4 mmol/L) 1, 2, 3, 4, 5.

Grading of Hypercalcemia

The grading of hypercalcemia is crucial in determining the severity of the condition and guiding management strategies. The CTCAE provides a standardized framework for grading hypercalcemia, which is based on serum calcium levels and clinical symptoms.

  • Grade 1 hypercalcemia is defined as calcium levels above the upper limit of normal (ULN) up to 11.5 mg/dL (2.9 mmol/L), representing mild elevation with no intervention typically required.
  • Grade 2 hypercalcemia ranges from >11.5 mg/dL to 12.5 mg/dL (>2.9 to 3.1 mmol/L), often requiring increased oral fluid intake and monitoring.
  • Grade 3 hypercalcemia is defined as calcium levels >12.5 mg/dL to 13.5 mg/dL (>3.1 to 3.4 mmol/L), which is considered severe and typically requires hospitalization, IV fluids, and possibly medications like bisphosphonates or calcitonin.
  • Grade 4 hypercalcemia is life-threatening with calcium levels >13.5 mg/dL (>3.4 mmol/L), requiring immediate intensive intervention to prevent serious complications like cardiac arrhythmias, seizures, or coma.

Management Strategies

The management of hypercalcemia depends on the underlying cause, severity, and clinical symptoms. Mild hypercalcemia may not require acute intervention, while severe hypercalcemia requires immediate attention. The use of denosumab, a monoclonal antibody that inhibits osteoclast formation and activity, has been shown to be effective in reducing serum calcium levels and alleviating renal dysfunction in patients with hypercalcemia associated with sarcoidosis 5.

Clinical Implications

The grading system helps clinicians assess severity and determine appropriate management strategies for patients with elevated calcium levels. It is essential to identify the underlying cause of hypercalcemia and treat it accordingly. In patients with primary hyperparathyroidism, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement 1.

Key Points

  • Hypercalcemia is graded on a scale from 1 to 4 based on serum calcium levels and clinical symptoms.
  • Grade 1 hypercalcemia is defined as calcium levels above the upper limit of normal (ULN) up to 11.5 mg/dL (2.9 mmol/L).
  • Grade 2 hypercalcemia ranges from >11.5 mg/dL to 12.5 mg/dL (>2.9 to 3.1 mmol/L).
  • Grade 3 hypercalcemia is defined as calcium levels >12.5 mg/dL to 13.5 mg/dL (>3.1 to 3.4 mmol/L).
  • Grade 4 hypercalcemia is life-threatening with calcium levels >13.5 mg/dL (>3.4 mmol/L).

References

Research

Hypercalcemia: A Review.

JAMA, 2022

Research

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hypercalcemia.

Medical science monitor : international medical journal of experimental and clinical research, 2022

Research

Hypercalcemia in the emergency department.

The American journal of the medical sciences, 2006

Research

Denosumab for the treatment of bisphosphonate resistant hypercalcemia in a hemodialysis patient.

Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia, 2017

Research

Efficacy of denosumab in the treatment of hypercalcemic renal dysfunction in sarcoidosis: a case report.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2024

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.