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<p class="ltrs-br-ltr-br-title">A Case of Lithium-Induced Symptomatic Hypercalcemia</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold">To the Editor:</span> Hypercalcemia has been associated with long-term lithium carbonate treatment, yet is often unrecognized.<span class="superscript">1</span> Symptoms of hypercalcemia can progress insidiously and can mimic psychiatric disturbances, eg, delirium and symptoms resembling mood disturbances.<span class="superscript">2,3</span> We report on a unique case of a lithium-treated patient presenting with depression-like symptoms secondary to hypercalcemia requiring lithium discontinuation.</p>
<p class="ltrs-br-ltr-br-body-text">&nbsp;</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold-italic">Case report.</span> Ms A, a 53-year-old woman, presented to the hospital in 2009 complaining of abdominal pain, nausea, constipation, and weakness of 1 week’s duration. Prescribed lithium carbonate 300 mg tid daily for 10 years for <span class="italic">DSM-IV-TR</span> bipolar disorder, she complained of fatigue, decreased concentration, decreased appetite, and muscle weakness for several weeks, prompting concerns of an exacerbation of depression. Admission laboratory studies revealed a marginally elevated serum lithium level at 1.27 mEq/L and hypercalcemia (13.5 mg/dL; normal range, 8.4–10.2 mg/dL). Serum phosphate was 3.2 mg/dL (normal range, 2.7–4.5 mg/dL), and magnesium was 1.35 mg/dL (normal range, 1.69–2.73 mg/dL).</p>
<p class="ltrs-br-ltr-br-body-text">Hypercalcemia workup revealed a parathyroid hormone (PTH) level of 24.4 pg/mL (normal range, 15–65 pg/mL) and a 25-hydroxy vitamin D level of 36.8 ng/mL (normal 32–100 ng/mL), both within normal limits. Blood urea nitrogen and creatinine levels were 9 mg/100 mL (normal range, 6–20 mg/100 mL) and 0.5 mg/dL (normal range, 0.5–0.1 mg/dL), respectively. A skeletal series and chest x-ray failed to identify malignancy or sarcoid as potential etiologies.</p>
<p class="ltrs-br-ltr-br-body-text">Intravenous fluids and furosemide were initiated to decrease serum calcium; Ms A was asymptomatic once levels reached 11.3 mg/dL. Lithium was discontinued and substituted with lamotrigine. Serum calcium levels normalized within 4 weeks following lithium discontinuation.</p>
<p class="ltrs-br-ltr-br-body-text">&nbsp;</p>
<p class="ltrs-br-ltr-br-body-text">Rates of lithium-induced hypercalcemia are estimated to be 5%–40%.<span class="superscript">3</span> Symptoms can consist of anorexia, nausea, constipation, mood disturbances, and, in severe cases, delirium, stupor, and coma. In the present case, the gastrointestinal symptoms and weakness prompted evaluation of medical etiologies, unearthing an underlying hypercalcemia ascribable to long-term lithium use. Other potential causes, eg, primary or secondary hyperparathyroidism, malignancy, sarcoid, and vitamin D toxicity, were eliminated by history and laboratory investigations.</p>
<p class="ltrs-br-ltr-br-body-text">Lithium may induce increased calcium reabsorbtion within the loop of Henle. Concurrently, lithium can alter feedback mechanisms within the parathyroid gland, impeding the suppression of PTH normally produced by hypercalcemia.<span class="superscript">1</span></p>
<p class="ltrs-br-ltr-br-body-text">Evidence of asymptomatic hypercalcemia can be monitored with continued lithium use. Traditionally, symptomatic cases may be managed with discontinuation of lithium along with use of diuretics and hydration, resulting in prompt symptom resolution. Recently, use of calciuric agents, eg, cinacalcet, has been advocated, allowing resolution of hypercalcemia without necessitating lithium discontinuation.<span class="superscript">4</span> Refractory cases, unresponsive to the above measures, may warrant parathyroidectomy.</p>
<p class="ltrs-br-ltr-br-body-text">Although the interval has not been established, clinicians should periodically monitor lithium-treated patients for hypercalcemia. Exacerbation of mood symptoms may be the initial sign of emerging hypercalcemia.</p>
<p class="ltrs-br-ltr-br-references-head"><span class="smallcaps">References</span></p>
<p class="references-references-text-1-9"><span class="htm-ref"> 1. </span>McHenry CR, Lee K. Lithium therapy and disorders of the parathyroid glands. <span class="italic">Endocr Pract</span>. 1996;2(2):103–109. <span class="pubmed-crossref"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15251551&dopt=Abstract">PubMed</a></span></p>
<p class="references-references-text-1-9"><span class="htm-ref"> 2. </span>Duggal HS, Singh I. Lithium-induced hypercalcemia and hyperparathyroidism presenting with delirium. <span class="italic">Prog Neuropsychopharmacol Biol Psychiatry</span>. 2008;32(3):903–904. <span class="pubmed-crossref"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=18234408&dopt=Abstract">PubMed</a> <a href="http://dx.doi.org/10.1016/j.pnpbp.2007.12.014">doi:10.1016/j.pnpbp.2007.12.014</a></span></p>
<p class="references-references-text-1-9"><span class="htm-ref"> 3. </span>Rifai MA, Moles JK, Harrington DP. Lithium-induced hypercalcemia and parathyroid dysfunction. <span class="italic">Psychosomatics</span>. 2001;42(4):359–361. <span class="pubmed-crossref"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11496029&dopt=Abstract">PubMed</a> <a href="http://dx.doi.org/10.1176/appi.psy.42.4.359">doi:10.1176/appi.psy.42.4.359</a></span></p>
<p class="references-references-text-1-9"><span class="htm-ref"> 4. </span>Sloand JA, Shelly MA. Normalization of lithium-induced hypercalcemia and hyperparathyroidism with cinacalcet hydrochloride. <span class="italic">Am J Kidney Dis</span>. 2006;48(5):832–837. <span class="pubmed-crossref"><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17060004&dopt=Abstract">PubMed</a> <a href="http://dx.doi.org/10.1053/j.ajkd.2006.07.019">doi:10.1053/j.ajkd.2006.07.019</a></span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Raphael J. Leo, MD</span></p>
<p class="ltrs-br-ltr-br-author"><a href="mailto:Rleomd@aol.com" target="_blank">Rleomd@aol.com</a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Mehak Sharma, BS</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">David A. Chrostowski, BS</span></p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Author affiliation:</span> Department of Psychiatry, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Potential conflicts of interest: </span>None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Funding/support: </span>None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Published online:</span> July 22, 2010 (<span class="doi">doi:10.4088/PCC.09l00917yel</span>).</p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">Prim Care Companion J Clin Psychiatry 2010;12(4):e1</span></p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">© Copyright 2010 Physicians Postgraduate Press, Inc.</span></p>
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