Background: Prolonged therapeutic exposure to lithium compounds can have adverse consequences on calcium homeostasis. A unique form of hyperparathyroidism appears to be causally linked to chronic lithium exposure. We provide a comprehensive review of relevant literature using a structured, evidence-based approach. Methods: Published data were identified from systematic electronic literature searches. References are assigned a level of evidence according to a validated classification schema. Results: Level III and V evidence supports an etiologic link between sustained lithium therapy and both hypercalcemia and hyperparathormonemia (grade C recommendation). Level V evidence supports the use of preoperative parathyroid imaging if a focused exploration is planned (grade C recommendation). Level V evidence supports the use of intraoperative parathyroid hormone monitoring to guide appropriate surgical therapy (grade C recommendation). There is conflicting and equally weighted level V evidence supporting a routine preoperative plan of bilateral neck exploration versus selective unilateral exploration (no recommendation). There may be a role for calcimimetic drug therapy as an alternate, nonsurgical means of controlling lithium-associated hyperparathyroidism (grade C recommendation). Conclusions: Evidence-based recommendations support screening of patients on chronic lithium therapy for hypercalcemia. Appropriate surgical therapy may consist of either a bilateral or a unilateral approach when performed by an experienced endocrine surgeon. Focused approaches should be guided by preoperative imaging and intraoperative hormone monitoring. Calcimimetic therapy is a potential alternative to parathyroidectomy.
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