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

Abstract

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.

Evaluation of parathyroid function and mineral metabolism in psychiatric patients using lithium salts

“…This condition is in agreement with the explanation proposed by some studies, which say that the HPT induced by Li has no relation to the given therapeutic dose, but rather with the presence of the medication in the body (34,35). The duration of the treatment increases the incidence of this clinical condition due to the cumulative power that Li has on the body (19,36).…”

“…In Li users who have been using it for at least 10 years, the prevalence of HPT was observed in approximately 10-15%, being higher in women (4:1), with the occurrence of both hyperplasia and adenomas of the parathyroid glands (18,19). In confirming diagnoses of lithium-associated hyperparathyroidism, therapeutic decisions should be individualized, taking as an initial choice suspension of Li in symptomatic patients.…”

Lithium Associated Hyperparathyroidism: An Evidence Based Surgical Approach

“…McHenry et al have reported that 80% of patients treated with lithium for 6 to 24 months experience a 10% increase in serum calcium levels. Christiansen et al re-ported that both serum calcium and PTH levels increased by 30% in the same population, and several other authors have also reported a 10% -60% increased prevalence of hypercalcemia and hyperparathyroidism in patients taking lithium [11][12][13][14].…”

Lithium safety and tolerability in mood disorders: a critical review

“…Even with normal or low levels of phosphate, 10-42% of patients develop some degree of serum hypercalcemia, and 29% are associated with elevated parathyroid hormone (PTH) 9 . The mechanism although uncertain, is probably due to the inactivation of the calcium-sensing receptor and the interference with intracellular second messenger signaling, leading to a primary increased release of PTH, with secondary raise of serum calcium 42 . In a retrospective study, total serum calcium was found to be higher than the reference value in 6% of patients; ionized calcium was higher in 25% and serum PTH in 23% 43 .…”

“…In a prospective study, patients who had never previously used lithium had elevated PTH and increased calcium reabsorption along with reduced excretion of calcium, unlike that commonly observed with primary hyperparathyroidism 45 . Multiple case reports associated lithium use and hyperparathyroidism with single or multiple adenomas of the parathyroid glands 42 . A previous study observed that total calcium levels were significantly higher in the lithium-treated group compared to patients who were treated with other psychotropic agents 35 .…”