ReviewLithium-associated hypercalcemia and hyperparathyroidism in the elderly: What do we know?
Introduction
Lithium, a monovalent cation and alkali metal, has been a mainstay of mood disorder treatment for over 40 years. It has been approved by the Food and Drug Administration for both the acute treatment of manic episodes and the maintenance treatment of bipolar disorder. Lithium has repeatedly been shown to decrease the number and severity of manic episodes (Prien et al., 1973, Geddes et al., 2004) as well as reduce the risk of mortality in patients with bipolar disorder (Cipriani et al., 2005). It remains the standard of treatment against which other mood stabilizing medications are compared (Bowden et al., 1994, for the Lamictal 605 Study Group). It is also used as an adjunctive agent in the treatment of patients with treatment-resistant unipolar and recurrent major depression. The therapeutic mechanisms by which lithium exacts its salutary effects on mood remain incompletely understood but are believed to involve inhibition of inositol monophosphatase and alterations in g proteins affecting second messenger systems in frontal cortex and the hypothalamus (Altamura et al., 2011, Shaldubina et al., 2001).
Lithium is also known to have multiple effects on renal physiology and on a number of endocrine systems (Grandjean and Aubry, 2009, McKnight et al., 2012). In particular, lithium treatment has been identified as having effects on calcium regulation and parathyroid functioning (Khandwala and Van Uum, 2006). Given that physiologic renal function declines after the fourth decade (Weinstein and Anderson, 2010), these effects may be of particular concern in older patients. In this report we review studies on lithium-induced hypercalcemia and hyperparathyroidism with a particular focus on the impact on elderly individuals.
Section snippets
Method
PubMed searches using the keywords ‘lithium’ and ‘hyperparathyroidism’ or ‘lithium’ and ‘hypercalcemia’ conducted in August 2010 yielded 128 articles and 100 articles, respectively. The resulting lists were combined and articles were selected for those that dealt with lithium-associated hyperparathyroidism and/or hypercalcemia. All relevant studies were also checked for additional citations, which were included if they dealt with lithium-associated hyperparathyroidism and/or hypercalcemia. Our
Results
The first case report of lithium-associated hyperparathyroidism appeared in 1973 (Garfinkel et al., 1973). The patient was a 52 year old woman who had been treated with lithium for 5.5 years and who developed hypercalcemia. While parathyroid hormone levels were not reported, the patient was found to have a parathyroid adenoma which was surgically resected. Christiansen et al. (1978) studied the effects of lithium on parathyroid hormone (PTH) levels and these authors were the first to report
Discussion
Most reports of lithium-induced hypercalcemia and hyperthyroidism have been published in non-psychiatric journals (Fig. 1), but lithium treatment is usually prescribed and monitored by a psychiatrist. It is important that psychiatrists be cognizant of lithium-associated hyperparathyroidism as a potential complication of lithium therapy. While many patients who experience lithium-associated hypercalcemia or lithium-associated hyperparathyroidism are asymptomatic, other patients may require
Limitations
This study was limited by the retrospective nature of our analysis of multiple studies. In addition, the studies were observational in nature, with varying design and typically a small sample size. There are no studies to date that have examined the prevalence of lithium-induced hypercalcemia and hyperparathyroidism in older patient cohorts. While older patients may be at greater risk for these complications of lithium therapy due to frequent co-morbid medical renal disease, there are no
Conclusions
Lithium-induced hypercalcemia and hyperparathyroidism are under-recognized potential complications of lithium treatment which may occur more frequently in older patients on lithium therapy. While mild and asymptomatic elevations in serum calcium and PTH levels can occur in patients treated with lithium, there is also the potential for symptomatic hypercalcemia and secondary hyperparathyroidism to occur. Older patients and patients with comorbid renal disease may be especially vulnerable to
Role of funding source
No funding source was used in preparation of this article.
Conflict of interest
Neither author has any conflicts of interest to disclose.
Acknowledgments
None.
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