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Abstract
BackgroundCurrent screening recommendations for early detection of lithium-associated hyperparathyroidism propose an exclusive measurement of serum albumin-adjusted calcium (Aac) concentration as a single first step. However, longitudinal data in patients with recurrent affective disorders suggest that increases in serum intact parathyroid hormone (iPTH) levels in lithium-treated patients may not necessarily be accompanied by a parallel increase in the concentration of Aac. If true, patients with an isolated increase in iPTH concentration above the reference range might be missed following current screening recommendations. Therefore, this study set out to examine key parameters of calcium metabolism, including iPTH and 25-hydroxycholecalciferol concentrations in patients with bipolar disorder that was or was not managed with lithium.MethodsSixty patients with bipolar disorder according to DSM-IV were enrolled, 30 of whom had received long-term lithium treatment (lithium group), whereas the other 30 patients were on psychopharmacological treatment not including lithium (non-lithium group) at the time of the study. Owing to exclusion criteria (e.g., lithium < 6 months, laboratory results indicative of secondary hyperparathyroidism), 23 bipolar patients composed the final lithium group, whereas 28 patients remained in the non-lithium group for statistical analyses.ResultsPatients in the lithium group showed a significantly higher concentration of iPTH compared to the non-lithium group (p < 0.05). Similarly, Aac concentrations were significantly increased in the lithium group compared to the non-lithium group (p < 0.05). However, in a multivariate linear regression model, group affiliation only predicted iPTH concentration (p < 0.05). In line with this, none of the four patients in the lithium group with an iPTH concentration above the reference range had an Aac concentration above the reference range.DiscussionThis study suggests that the biochemical characteristics between primary hyperparathyroidism and lithium-induced hyperparathyroidism differ substantially with regard to regulation of calcium homeostasis. As such, current screening practice does not reliably detect iPTH concentrations above the reference range. Therefore, further research is needed to elucidate the consequences of an isolated iPTH concentration above the reference range in order to develop the most appropriate screening tools for hyperparathyroidism in lithium-treated patients with bipolar disorder.
Highlights
Current screening recommendations for early detection of lithium-associated hyperparathyroidism propose an exclusive measurement of serum albumin-adjusted calcium (Aac) concentration as a single first step
In case of lithium treatment, a decrease in parathyroid sensitivity to calcium has been suggested as the principal mechanism of action for the increased secretion of parathyroid hormone resulting in hypercalcemia, the biochemical hallmark of primary hyperparathyroidism (Haden et al 1997)
Study population Thirty (30) patients with bipolar I/II disorder, who had been on lithium for at least 6 months as well as 30 bipolar patients without current lithium treatment were enrolled in the study
Summary
Current screening recommendations for early detection of lithium-associated hyperparathyroidism propose an exclusive measurement of serum albumin-adjusted calcium (Aac) concentration as a single first step. One of the more recent studies suggests that following 6 months of lithium treatment, patients have significantly increased parathyroid hormone concentrations without an increase in serum calcium levels (Mak et al 1998). This ‘normocalcemic’ subtype of lithiuminduced hyperparathyroidism will remain unrecognized if calcium is used as the sole and primary screening instrument as is currently recommended. In a community-based cohort of elderly men, higher (and high normal) plasma PTH levels were associated with a higher risk of cardiovascular mortality in the absence of hypercalcemia (Hagstrom et al 2009) Missing these cases of isolated higher parathyroid levels is of particular concern as bipolar disorder per se is associated with an increased risk of cardiovascular mortality (Fiedorowicz et al 2008). We set out to answer the following hypotheses: Serum iPTH concentrations in patients with bipolar disorders are increased when treated with lithium compared to those patients treated with other drugs
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