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Publications

Published: 5 September 2014

Hyperparathyroidism and Hypercalcaemia with Lithium Treatment

Prescriber Update 35(3): 37-38
September 2014

Key Messages

  • Up to 10% of patients on long-term lithium treatment experience hypercalcaemia.
  • Serum calcium levels should be measured at least once a year in patients taking lithium.
  • Parathyroid hormone levels should be measured in patients with raised calcium levels.
  • Patients with raised calcium and parathyroid hormone levels should be referred for specialist treatment.
  • Patients with raised calcium levels only, should be monitored more closely unless the level exceeds 2.75mmol/L in which case lithium treatment should be stopped.


Lithium-associated hyperparathyroidism (LAH) was first described in 19731. However it is unclear if lithium causes the disease or reveals an underlying hyperparathyroidism (HPT)1. There is a wide spectrum of abnormalities in calcium homeostasis in patients taking lithium which range from overt hyperparathyroidism to hypercalcaemia with normal parathyroid hormone levels1.

In patients taking lithium the prevalence of lithium-associated hyperparathyroidism is estimated at 4.3-6.3%, which is higher than the prevalence of HPT in the general population (1-4 in every 1,000 people)1. Up to 10% of patients on long-term lithium treatment develop hypercalcaemia2.

Patients with LAH are often asymptomatic. However, when symptoms are reported these include: fatigue, constipation, nephrolithiasis, bone pain and abdominal pain3. Patients with LAH often present with serum calcium levels ranging from slightly above normal (normal range 2.125-2.55mmol/L, depending on the laboratory) to over 3.75mmol/L. The PTH levels in these patients range from high normal to several times the upper limit of normal (normal range 10-55 pg/ml, depending on the laboratory)3. Multiglandular disease is more often reported in LAH compared to sporadic cases of HPT1.

Hypercalcaemia has been reported after one day of lithium treatment. Overt HPT has been reported after one to two months of lithium treatment. Cases of HPT have also been reported after discontinuation of lithium treatment1.

Patients taking lithium should have their serum calcium levels measured at least once per year2. The frequency of monitoring should be increased in patients with an abnormal result or those with risk factors for HPT such as a family history2. If raised calcium levels are detected then the serum parathyroid level should be measured; if this is also raised the patient should be referred for specialist treatment3.

If serum calcium levels are raised above 2.75mmol/L with normal parathyroid hormone levels lithium treatment should be stopped3. Calcium levels should be measured weekly to ensure that they return to within the normal range3.

Re-treatment with lithium may be considered if no effective alternatives are available, however the patient’s calcium levels must be closely monitored. For full details of the monitoring recommendations see the data sheets for lithium on the Medsafe website (www.medsafe.govt.nz/Medicines/infoSearch.asp).

References
  1. Szalat A, Mazeh H and Freund HR. 2009. Lithium-associated hyperparathyroidism: report of four cases and review of the literature. European Journal of Endocrinology 160: 317-323.
  2. McKnight R, Adida M, Budge K. 2012. Lithium toxicity: a systematic review and meta-analysis. The Lancet 379: 721-728.
  3. Lehmann SW, Lee J. 2013. Lithium-associated hypercalcaemia and hyperparathyroidism in the elderly: what do we know? Journal of Affective Disorders 146: 151-157.
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