Lithium-associated hypercalcemia and hyperparathyroidism: A systematic review and meta-analysis

We aimed to review and summarise the existing human literature on the association between lithium and hyperparathyroidism. A systematic literature search was carried out according to PRISMA guidelines (last search 27 February 2024), using MEDLINE, Web of Science, Embase and the Cochrane Library. A meta-analysis was performed to determine the prevalence of lithium-associated hypercalcemia (LAH_ca) in lithium-treated patients. The pooled prevalence of LAH_ca based on total calcium and ionised calcium was comparable, at 3.17% and 4.23%, respectively. Calcium, and PTH if the patient is hypercalcaemic, is insufficiently measured in lithium-treated patients in clinical practice. Lithium use is associated with higher calcium and PTH levels, as well as a higher incidence of hyperparathyroidism. There is a high prevalence of multiglandular disease in lithium-associated hyperparathyroidism (LAH), with a pooled prevalence of 51.28%. Parathyroid surgery and cinacalcet are effective treatments for LAH. Regarding lithium discontinuation, there is anecdotal but conflicting evidence suggesting that it can result in the resolution of LAH in selected cases. Lithium treatment increases the risk of hyperparathyroidism, a treatable complication with a pooled prevalence of around 4%, compared to 0.5% in the healthy population.