Lithium-associated hyperparathyroidism: a systematic review of prevalence and surgical outcomes

Lithium remains one of the most effective maintenance treatments for bipolar disorder. However, disturbances in calcium homeostasis including hypercalcemia and lithium-associated hyperparathyroidism (LHPT) have increasingly been recognized as endocrine complications of chronic lithium therapy. The prevalence, pathophysiology, and optimal surgical management of LHPT remain incompletely defined. This systematic review aims to synthesize the available evidence on prevalence, pathophysiology, and surgical outcomes in LHPT.

We conducted a systematic review according to PRISMA guidelines. Five databases (MEDLINE, Embase, Cochrane Library, Web of Science, and PsycINFO) were searched. Studies reporting hypercalcemia or hyperparathyroidism in adult patients receiving lithium therapy were eligible for inclusion. Surgical case series reporting parathyroidectomy in LHPT were analyzed separately.

A total of 5,483 records were identified, of which 125 studies met the inclusion criteria. Hypercalcemia occurred in 7.2% (423/5,853) and HPT was confirmed in 4.8% (156/3,239) of lithium-treated patients. Multiglandular disease was identified in 25-83% of surgical cases, substantially higher than the 15-20% observed in sporadic HPT. Bilateral neck exploration was performed in the majority of surgical series. Postoperative cure rates ranged from 58% to 100%, with recurrence rates of approximately 16% at 10 years.

LHPT represents a clinically significant endocrine complication characterized by heterogeneous pathological patterns. The elevated prevalence of multiglandular disease has important implications for surgical planning. Given the high proportion of multiglandular involvement, surgeons should maintain a low threshold for bilateral neck exploration, particularly in patients with prolonged lithium exposure or intraoperative findings suggestive of multiple gland involvement.