Med/Psych Update

Lithium-associated hypercalcemia: Monitoring and management

Current Psychiatry. 2022 December;21(12):36-40 | doi: 10.12788/cp.0311

References

1. Meehan AD, Udumyan R, Kardell M, et al. Lithium-associated hypercalcemia: pathophysiology, prevalence, management. World J Surg. 2018;42(2):415-424.

2. McKnight RF, Adida M, Budge K, et al. Lithium toxicity profile: a systematic review and meta-analysis. Lancet. 2012;379(9817):721-728.

3. Shapiro HI, Davis KA. Hypercalcemia and “primary” hyperparathyroidism during lithium therapy. Am J Psychiatry. 2015;172(1):12-15.

4. Lerena VS, León NS, Sosa S, et al. Lithium and endocrine dysfunction. Medicina (B Aires). 2022;82(1):130-137.

5. Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician. 2003;67(9):1959-1966.

6. Yeh MW, Ituarte PH, Zhou HC, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013;98(3):1122-1129.

7. Dandurand K, Ali DS, Khan AA. Primary hyperparathyroidism: a narrative review of diagnosis and medical management. J Clin Med. 2021;10(8):1604.

8. Mifsud S, Cilia K, Mifsud EL, et al. Lithium-associated hyperparathyroidism. Br J Hosp Med (Lond). 2020;81(11):1-9.

9. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170.

10. Mieebi WM, Solomon AE, Wabote AP. The effect of tourniquet application on serum calcium and inorganic phosphorus determination. Journal of Health, Medicine and Nursing. 2019;65:51-54.

11. Awad SS, Miskulin J, Thompson N. Parathyroid adenomas versus four-gland hyperplasia as the cause of primary hyperparathyroidism in patients with prolonged lithium therapy. World J Surg. 2003;27(4):486-488.

12. Farndon JR. Postoperative complications of parathyroidectomy. In: Holzheimer RG, Mannick JA, eds. Surgical Treatment: Evidence-Based and Problem-Oriented. Zuckschwerdt; 2001. Accessed October 25, 2022. https://www.ncbi.nlm.nih.gov/books/NBK6967

Treatment: Continue lithium?

There are several options for treating LAH. Lithium may be continued or discontinued following close monitoring of calcium and PTH levels, with or without active interventions such as surgery or pharmacotherapy, and as deemed appropriate after consultation with an endocrinologist. The decision should be informed by evaluating the risks and benefits to the patient’s physical and mental health. LAH can be reversed by discontinuing lithium, but this might not be the case in patients receiving long-term lithium therapy, especially if their elevated calcium levels are associated with parathyroid adenomas or hyperplasia. Hence, close monitoring of calcium and PTH is required even after discontinuing lithium.^3,8

Surgical treatment. The primary treatment of LAH and primary hyperparathyroidism is parathyroidectomy. The possibility of recovery after parathyroidectomy for primary hyperparathyroidism is 60% to 80%, though a small proportion of patients might experience recurrence. This figure might be higher for LAH, because it is more likely to affect multiple glands.^1,11 Other potential complications of parathyroidectomy are recurrent laryngeal nerve injury causing paralysis of vocal cords leading to hoarseness of voice, stridor, or aspiration, and local hematoma and hypocalcemia (requiring vitamin D and/or calcium supplements).¹²

Pharmacotherapy. Cinacalcet is a calcimimetic drug that decreases the reset point of the calcium-sensing receptor. It can be used if a patient is not suitable for or apprehensive about surgical intervention.^1,8

Bottom Line

Calcium levels should be regularly monitored in patients receiving lithium. If calcium levels are persistently high, parathyroid hormone levels should also be measured. Management of lithium-associated hypercalcemia includes watchful waiting, discontinuing lithium, parathyroidectomy, and pharmacotherapy with cinacalcet.

Related Resources

Laski M, Foreman R, Hancock H, et al. Lithium: an underutilized element. Current Psychiatry. 2021;20(12):27-30,34. doi:10.12788/cp.0193
Pelekanos M, Foo K. A resident’s guide to lithium. Current Psychiatry. 2021;20(4):e3-e7. doi:10.12788/cp.0113

Drug Brand Names

Cinacalcet • Sensipar