To Örebro University

Introduction: Lithium-associated hyperparathyroidism (LHPT) was first reported in 1973. It remains unclear if this is a specific endocrinopathy or separate simultaneous medical conditions. Definitive management for lithium-treated patients with calcium dysfunction has yet to be established (1).

Method: We conducted this systematic review of all available studies in English which provide patient material from the adult population (>18 years) illustrating lithium’s association in the development of hypercalcaemia and/or hyperparathyroidism. A predefined review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD 395676). The search used five major databases: Medline, EMBASE, Cochrane Library, PsycINFO, and Web of Science, between 1973 to January 2023, using the keywords hyperparathyroidism, lithium, hypercalcaemia, hypocalcaemia. Review articles and abstracts were excluded.

Result: Of the initial 5418 searches, 169 articles were included for final analysis. Prevalence of hypercalcaemia is reported in approximately 20-30% of lithium-treated patients. Lithium gives moderate increases in calcium levels, with or without elevations in parathyroid hormone. Paradoxically, lithium may be skeletal protective. Multiglandular disease is more common in LHPT than in pHPT, most often consisting of hyperplastic glands. In surgical cases, bilateral exploration is often preferred. Follow-up times are relatively short. No randomised surgical studies exist.

Discussion:

• LHPT appears to be a common endocrinopathy.• Lithium patients with tendency to calcium dysfunction should be carefully monitored.• More radical surgery may lead to health benefits.• Randomized controlled trials should be conducted to identify optimal treatment in patients with LHPT.