SAT-355 Severe Symptomatic Hypocalcemia Related to Cinacalcet Administration Introduction

BACKGROUND: Cinacalcet, a class of drug used to treat secondary hyperparathyroidism due to end-stage renal disease, is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. This drug acts as a calcimimetic agent by allosteric activation of the calcium-sensing receptor that is expressed in various tissues. Common side effects of cinacalcet include nausea, vomiting, diarrhea and weakness. Although mild hypocalcemia is a common side effect, severe hypocalcemia is rare. Case Presentation: A 61-year-old man was evaluated for treatment of type I diabetes mellitus. He reported several months of progressive fatigue, muscle weakness, and paresthesia of his hands and feet. He was prescribed cinacalcet for a parathyroid disorder since 2014 and his previous physician increased the dose of cinacalcet about 2 months ago from 60mg daily to 120mg daily. Since that time his paresthesias have been more severe. Physical examination: normal vital signs, Chvostek’s and Trousseau’s signs were positive. Rest of the examination was normal. Laboratory: corrected serum calcium (Ca) of 6.7 mg/dL (ref 8.6–10.0), down from 7.6 mg/dL 2 months earlier. Additional laboratory: Ionized Ca 3.4 mg/dL (ref 4.5–5.6), PTH 68 pg/mL (ref 15–65), 25-OH vitamin D 37 ng/mL (ref 29–100), phosphorus 4.9 mg/dL (ref 2.5–4.5) and calculated GFR 97 mL/min. Cinacalcet was stopped. The patient was treated with calcium intravenously in the ICU resulting in normal serum calcium levels after 36 hours of treatment and complete resolution of symptoms. He was discharged on oral calcitriol and calcium supplementation, which was discontinued within 1 week of discharge. Discussion: In vast majority of cases hypocalcemia associated with cinacalcet therapy are mild and self-limited. Generally hypocalcemia develops within 16 weeks of starting therapy and resolves spontaneously within 2 weeks. This case is unusual in that the hypocalcemia occurred years after starting therapy and the patient experienced severe symptoms, undiagnosed for a prolonged period of time and required admission for close monitoring. Additionally, this patient was without the most common risk factor for cinacalcet-associated hypocalcemia which was secondary hyperparathyroidism, and he had normal renal function. The marked decrease in serum Ca levels may be related to his low baseline serum Ca levels and due to the recent increase in cinacalcet dose. However this has not always verified based on retrospective studies. Interestingly the cinacalcet dose was increased in up to 14% of patients with severe hypocalcemia (<7.5 mg/dL) and even in this population severe symptomatic hypocalcemia symptoms were rare. In conclusion, clinicians should closely monitor patients on calcimimetic drugs for hypocalcemic symptoms although mild asymptomatic hypocalcemia may resolve without intervention.