Hypercalcemia and "primary" hyperparathyroidism during lithium therapy

A 66-year-old Caucasian man with schizoaffective disorder was admitted to the psychiatric unit for a relapse of psychotic mania. The patient’s syndromal affective and psychotic symptoms had been in remission for the previous 11 years, duringwhich time the patient had been treatedwith lithium, 1200 mg/day, and olanzapine, 15 mg/day. He took no additional medications or supplements andwas otherwise healthy. Four months before admission, routine primary care screening revealed an elevated serum calcium level, at 11.0 mg/dL (reference range, 8.6–10.2 mg/dL). Records showed elevated calcium levels dating back 9 years. Three months before admission, the patient’s serum lithium levelwas 1.0mmol/L (reference range, 0.6–1.2 mmol/L) and his intact parathyroid hormone (iPTH) level was 92.2 pg/mL (reference range, 12–88 pg/mL). His primary care provider conferredwith an endocrinologist, who noted that lithium therapy is a well-documented cause of hypercalcemia and suggested discontinuing lithium. Lithiumwas discontinued and divalproex initiated at 1000 mg/day, 17 days before admission.At admission, the emergency department evaluation noted pressured speech, disorganized thought process, religious preoccupations, paranoia, five sleepless nights, elevated energy, labile mood, and uncharacteristically impulsive behaviors. Laboratory studies showed a serum calcium level of 10.7 mg/dL. Results of physical examination, comprehensive metabolic screening, CBC, and toxicology screeningwere otherwisenormal, aswas thepatient’s thyroidstimulating hormone level. An increase in the dosage of divalproex to 2000 mg/day, along with trials of olanzapine (20 mg/day), haloperidol (15 mg/day), and risperidone (4.5 mg/day), were ineffective in controlling the patient’s mania. The endocrinologydepartmentwas consulted once again to determine the risks and advisability of reinstituting lithium. The consultant recommended a further hypercalcemia workup. On hospital day 10, the patient’s calcium level normalized to 9.8 mg/dL, while his iPTH level was an inappropriately high-normal 76.7 pg/mL. His urinary calcium level was elevated at 362.5mg/24 hours (reference range, 100–300 mg). His 25-hydroxy vitamin D level was noted tobe lowat 21.0ng/mL(reference range, 30–100ng/mL). A technetium-99m sestamibi scan revealed increased uptake in one parathyroid gland, suggestive of adenoma. Bone mineral density testing by DXA (dual-energy X-ray absorptiometry) scan showed mild osteopenia in the left hip only (T-score51.4 SD). ECG results were unremarkable. Based on hypercalciuria and enhanced localized parathyroid uptake, the consultant diagnosed primary hyperparathyroidism. Because it was considered asymptomatic, surgical intervention was not deemed necessary. The consultant concluded that it was a reasonable risk to reinitiate lithium with follow-up monitoring in the endocrinology clinic. Lithium was restarted on hospital day 10 and titrated to the previously effective dosage. The patient’s manic psychosis remitted, and he was discharged on a regimen of lithium, 1200 mg/day, and risperidone, 3 mg/day. The patient remained in psychiatric remission at the 5week and 15-week follow-up appointments. Twelve weeks after discharge, his serum calcium and iPTH levels were again elevated at 10.7 mg/dL and 86.3 pg/mL, respectively, and his serum lithium level was 0.98 mmol/L.