Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder

Abstract

ObjectivesAlthough potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow‐up.MethodsWithin the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum‐lithium (se‐Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid‐stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients.ResultsAmong 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07–11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow‐up: lithium users = 2.5, reference patients = 1.4).ConclusionsSeverely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long‐term lithium treatment are prone to detection bias.

Surgical strategy in lithium‐associated hyperparathyroidism: A population‐based study

“…This, in association with a higher grade of biochemical monitoring coupled to lithium medication, carries a risk of detection bias with overestimating differences compared to the non-LAH group. 3 As expected, neuropsychiatric disorders were overrepresented in the LAH group. Injuries and intoxications were also more common.…”

“…Lithium carbonate is the most extensively evaluated long-term mood-stabilizing treatment for preventing recurrences of bipolar and depressive disorders 1,2 and is usually well-tolerated. 3,4 Lithium-associated hyperparathyroidism (LAH) is a recently recognized problem. 5 Regular monitoring of calcium is recommended yet still not included in all practice guidelines for managing patients on lithium, which likely explains the wide variation in the reported prevalence of LAH.…”

“…7 Inactivation of the calcium-sensing receptor and interference with intracellular second messenger signaling are suggested to be underlying factors for LAH. 3 The risk of LAH depends on the duration of lithium exposition; however, on occasion, pre-existing subclinical primary hyperparathyroidism (PHPT) may be revealed by initiating lithium treatment. 3,8 Bipolar disorder per se has not been associated with hypercalcemia.…”

“…3,8 Bipolar disorder per se has not been associated with hypercalcemia. 3,6 The presentation of LAH may differ from that of sporadic PHPT. Multiglandular disease is more common.…”

“…3 The risk of LAH depends on the duration of lithium exposition; however, on occasion, pre-existing subclinical primary hyperparathyroidism (PHPT) may be revealed by initiating lithium treatment. 3,8 Bipolar disorder per se has not been associated with hypercalcemia. 3,6 The presentation of LAH may differ from that of sporadic PHPT.…”