Lithium‐Associated Hypercalcemia: Pathophysiology, Prevalence, Management

Abstract

BackgroundLithium-associated hypercalcemia (LAH) is an ill-defined endocrinopathy. The aim of the present study was to determine the prevalence of hypercalcemia in a cohort of bipolar patients (BP) with and without concomitant lithium treatment and to study surgical outcomes for lithium-associated hyperparathyroidism.MethodsRetrospective data, including laboratory results, surgical outcomes and medications, were collected from 313 BP treated with lithium from two psychiatric outpatient units in central Sweden. In addition, data were collected from 148 BP without lithium and a randomly selected control population of 102 individuals. Logistic regression was used to compare odds of hypercalcemia in these respective populations.ResultsThe prevalence of lithium-associated hypercalcemia was 26%. Mild hypercalcemia was detected in 87 out of 563 study participants. The odds of hypercalcemia were significantly higher in BP with lithium treatment compared with BP unexposed to lithium (adjusted OR 13.45; 95% CI 3.09, 58.55; p = 0.001). No significant difference was detected between BP without lithium and control population (adjusted OR 2.40; 95% CI 0.38, 15.41; p = 0.355). Seven BP with lithium underwent surgery where an average of two parathyroid glands was removed. Parathyroid hyperplasia was present in four patients (57%) at the initial operation. One patient had persistent disease after the initial operation, and six patients had recurrent disease at follow-up time which was on average 10 years.ConclusionThe high prevalence of LAH justifies the regular monitoring of calcium homeostasis, particularly in high-risk groups. If surgery is necessary, bilateral neck exploration should be considered in patients on chronic lithium treatment. Prospective studies are needed.

Hypercalcemia and cancer: Differential diagnosis and treatment

“…Hypercalcemia caused by either thiazide diuretics or lithium resolves with cessation of the medication; however, this may be particularly difficult in cases of bipolar disease managed with lithium when there are limited treatment alternatives. 20 The mechanism of lithium's effect on parathyroid function is not well delineated but is thought to be related to the calcium-sensing mechanism of the glands. 21 Well-selected patients with lithium-induced hypercalcemia may benefit from subtotal parathyroidectomy and often demonstrate multigland disease.…”

Examination of the Etiologic Causes in Patients Presenting with Elevated Parathormone

“…According to the investigations performed; vitamin D deficiency was found in 88 (64.2%), PHPT in 38 (27.7%), FHH in 8 (5.8%), and CRF in 3 (2.2%) patients. The mean creatinine values of the patients was found as 0.73±0.16 (0.4-1.5), the mean calcium value as 9.90±0.87 (8)(9)(10)(11)(12), the mean phosphorus value as 3.09±0.60 (1.9-5.1), the mean PTH value as 176.2±72.5 (90-476), and the mean vitamin D level as 15±11.8 (2.4-65). The mean 24-h urine calcium level was found as (n=44) 259±178.9 (22-910) and the mean calcium clearance (n=86) as 0.011±0.009 (0.007-0.431).…”

“…While urine calcium excretion is increased in PHPT, it is decreased in FHH because of the mutation in calcium sensitizer receptors (CaSR) (7). Similarly the use of lithium may antagonize CaSR, causing hyperparathyroidism, hypercalcemia, and hypercalciuria (8).…”

The Effects of Lithium on Calcium and Parathormone Levels: A Cross-sectional Study with Healthy Controls

“…2002, Kallner ve Petterson 1995, Meehan ve ark. 2015, Meehan ve ark. 2018, Stancer ve Forbath 1989, Twigt ve ark.…”

“…Hipoalbuminemi varlığında, toplam serum Ca konsantrasyonunun ölçümü hiperkalseminin gerçek prevalansını değerlendirmede yetersiz kalmasına rağmen bazı çalışmalarda iyonize Ca düzeyi değerlendirilmeksizin toplam Ca düzeyi ölçülmüştür (Bendz ve ark. 1996, Meehan ve ark. 2018.…”