What is the relationship between lithium and hypercalcemia (elevated calcium levels)?

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Last updated: February 27, 2025View editorial policy

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From the Guidelines

Lithium therapy can cause hypercalcemia, and regular monitoring of calcium levels is crucial for patients taking lithium, with baseline and follow-up measurements every 6-12 months. This is because lithium can affect calcium metabolism, potentially leading to hyperparathyroidism and elevated calcium levels in some patients 1. When initiating lithium therapy, baseline laboratory assessment should include serum calcium levels, among other tests, to establish a reference point for future monitoring 1.

Key Considerations for Lithium and Calcium Monitoring

  • Baseline calcium levels should be measured before starting lithium therapy
  • Regular monitoring of calcium levels is recommended every 6-12 months during lithium treatment
  • Patients on lithium should maintain consistent calcium intake through diet or supplements to avoid fluctuations in lithium levels
  • Symptoms like excessive thirst, frequent urination, bone pain, or confusion may indicate disturbances in calcium or lithium levels and should be reported to a healthcare provider

The interaction between lithium and calcium is significant because both affect kidney function and are regulated through similar pathways in the renal tubules 1. High calcium intake might reduce lithium levels, while low calcium could potentially increase lithium retention, highlighting the importance of consistent calcium intake for patients on lithium therapy. By prioritizing regular monitoring and maintaining stable calcium levels, healthcare providers can help mitigate the risk of hypercalcemia and ensure the safe and effective use of lithium for treating bipolar disorder.

From the Research

Relationship Between Lithium and Hypercalcemia

The relationship between lithium and hypercalcemia is well-documented in various studies. Key findings include:

  • Lithium therapy can lead to hypercalcemia, with a 4 to 6-fold higher risk of primary hyperparathyroidism compared to the general population 2, 3.
  • The mechanism of lithium-induced hypercalcemia involves the stimulation of parathyroid cell proliferation through the Wnt pathway, leading to increased serum calcium and parathyroid hormone (PTH) levels 2, 3.
  • Hypercalcemia associated with lithium therapy can manifest as a hypercalcemia-hypocalciuria syndrome, which may regress with lithium discontinuation 2.
  • Regular monitoring of calcium levels is crucial in patients on lithium therapy, as early recognition of lithium-associated hyperparathyroidism can improve outcomes 3, 4, 5.

Prevalence and Risk Factors

Studies have reported varying prevalence rates of hypercalcemia in patients on lithium therapy, ranging from 10-60% 4. Risk factors for lithium-associated hyperparathyroidism include:

  • Duration of lithium exposure, with longer treatment durations associated with higher ionized calcium levels 5.
  • Pre-existing thyroid autoimmunity, which may increase the risk of hypothyroidism and hyperparathyroidism in lithium-treated patients 2.

Clinical Implications

The clinical implications of lithium-associated hypercalcemia include:

  • Increased morbidity, particularly in patients with chronic kidney disease or interstitial tubule nephritis 2, 3.
  • Need for regular monitoring of serum calcium, PTH, and other biochemical parameters in patients on lithium therapy 2, 3, 4, 5.
  • Importance of careful patient selection and long-term follow-up to reduce morbidity associated with lithium-induced hyperparathyroidism 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lithium-associated hyperparathyroidism.

British journal of hospital medicine (London, England : 2005), 2020

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.

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