Lithium-associated hyperparathyroidism: report of four cases and review of the literature

Context: Lithium-associated hyperparathyroidism (LAH) was first described in 1973 but many issues remain in question regarding the pathophysiology as well as the appropriate management of this condition. Objective: Report of four new cases and review of the literature. Results: We describe two males and two females, treated for more than 10 years with lithium due to bipolar disorder, who developed LAH. All underwent parathyroidectomy. In three cases (75%), pathology revealed multiglandular disease, with hyperplasia or two parathyroid adenomas. We observed a cure status in three (75%) of the operated patients. The fourth patient had a residual disease, but had controlled hypercalcemia under the calcimimetic drug cinacalcet. We also observed the association of LAH with incidental papillary thyroid carcinoma in two patients. Review of the literature identified a higher prevalence of LAH in women than men (four out of one) and a controversy in regard to the prevalence of multiglandular disease. As a result, there is no consensus regarding the preferred surgical procedure. The use of cinacalcet as an effective treatment of LAH was previously described in only five cases. Conclusion: In our view, there are apparently two different mechanisms leading to LAH: exacerbation of a pre-existing state of hyperparathyroidism and multiglandular disease. For uncontrolled hypercalcemia, parathyroidectomy is recommended. The issue of routine four-gland exploration and subtotal parathyroidectomy versus intraoperative PTH-determination-guided excision of enlarged glands is still unresolved. The use of the recently developed calcimimetics may offer an alternative to patients who are not candidates for surgery.