Case of alfacalcidol‐induced hypercalcemia presenting as bipolar disorder

Abstract

WE PRESENT THE case of a patient previously diagnosed with bipolar disorder, including manic and depressive episodes, that turned out to be due to hypercalcemia induced by alfacalcidol. A 55-year-old Japanese woman developed depressive symptoms 4 years previously and she started dosulepin 75 mg/day. At that time, a prednisolone treatment for autoimmune hemolytic anemia was administered coupled with alfacalcidol 1 µg/week and risedronate 17.5 mg/week for prevention of steroid-induced osteoporosis. Two years later, she showed symptoms including decreased need for sleep and unrestrained buying sprees. She was diagnosed as having bipolar disorder. Dosulepin was discontinued and lithium carbonate 200 mg/day was started. Hypomania gradually disappeared. However, she experienced the recurrence of a manic episode 1 year later, and she was admitted to a psychiatric hospital. With an intravenous infusion (1500 mL/day of hypotonic infusion), her psychiatric state promptly improved. Four weeks after the discharge, however, she showed severe symptoms of depression. Then she was admitted to our hospital. As her dehydration was severe, we performed intravenous infusion. Depressive symptoms gradually disappeared, although the disorientation was relatively prolonged until the full remission. Her psychiatric prescriptions at discharge were lithium carbonate 400 mg, quetiapine 100 mg and flunitrazepam 1 mg. Eighteen months after discharge, she suddenly began to suffer from insomnia, restlessness, inhibition of thought, forgetfulness, loss of appetite, impaired tongue movement, dry mouth, and trembling. She also experienced episodic visual hallucinations of flying birds and severe disorientation. Her serum calcium level was 15.3 mg/dL (normal range 9.0–10.5). Intact parathyroid hormone, vitamin D, parathyroid hormone-related peptide and lithium level were within normal range at admission. We suspected alfacalcidol-induced hypercalcemia and stopped alfacalcidol and lithium administrations. The treatment of hypercalcemia was begun with normal saline infusion, zolendronate and calcitonin, and then her psychiatric symptoms improved significantly. No recurrence was observed without any psychotropic agents for at least 14 months after discharge. Continuation of lithium therapy may result in chronic hypercalcemia by raising the threshold of the Ca-sensing mechanism within the parathyroid gland responsible for shutting off the parathyroid hormone (PTH) secretion.1 Consequently, PTH secretion continues despite elevated Ca level. In the current case, lithium-induced hypercalcemia could be ruled out because serum PTH was within the normal limit when the elevated serum Ca level was observed. Hypercalcemia blocks anti-diuretic hormone signaling, leading to dehydration, and dehydration further promotes hypercalcemia through decreased Ca clearance. The improvement of apparent manic and depressive episodes was tightly linked with the correction of hypercalcemia. However, whether all the affective episodes could be explained by hypercalcemia or not is unclear, as her serum Ca level had not been quantified until the current admission. To our knowledge, this is the first reported case of hypercalcemia presenting with both manic and depressive episodes, and also the first to report an affective disorder induced by alfacalcidol administration. Our patient provided informed consent for publication of her case.