Severe Hypercalcemia in a Patient with Familial Hypocalciuric Hypercalcemia with a Rare Calcium-Sensing Receptor (CASR) R185Q Mutation Treated with Cinacalcet
Presentation Number: MON 304
Date of Presentation: April 3rd, 2017
Daniel Thomas Bond* and Andrew Orville Paulus
Wright State University, Dayton, OH
Familial hypocalciuric hypercalcemia (FHH) patients rarely present with symptomatic hypercalcemia. We describe a case of FHH associated with a rare CASR mutation with symptomatic hypercalcemia treated with cinacalcet.
A 26 year-old otherwise healthy women was referred to endocrinology for evaluation of hypercalcemia. She reported a strong family history of hypercalcemia in her sister, mother, maternal uncle and cousin although she was unsure of a genetic cause. Some family members had undergone parathyroid surgery, but it was unclear if this improved their calcium levels. She had symptoms of nausea, headache, constipation and fatigue. Her serum calcium was 13.7 mg/dL (normal 7.9-10), serum phosphorous was 2.6 mg/dL (normal 2.5-4.5) and albumin was 4.3 g/dL (normal 3.4-5). The intact parathyroid hormone (PTH) was 43.8 pg/mL (normal 15.0-65.0), vitamin D 25-hydroxy was 26.2 ng/mL (normal 30.0-100.0). Fractional excretion of calcium was 0.0046 and Tc-99m sestamibi parathyroid scintigraphy scan revealed no findings to suggest parathyroid adenoma. Genetic testing of the calcium-sensing receptor (CASR) was subsequently performed and demonstrated a heterozygous R185Q mutation confirming the diagnosis of FHH.
A heterozygous R185Q mutation is a rare inactivating CASR mutation which has been associated with calcium levels ranging from 10.88 mg/dL to 13.7 mg/dL in affected families with FHH(1). Interestingly, this heterozygous mutation has been shown to cause neonatal severe hyperparathyroidism (NSHPT) which is usually caused by a homozygous inactivating CASR mutation(2). There are case reports of infants with NSHPT due to heterozygous CASR R185Q mutations successfully treated with cinacalcet(2).
However, there are no case reports describing the use of cinacalcet in adults with symptomatic hypercalcemia due to FHH and CASR R185Q mutation. Cinacalcet works as an allosteric CASR agonist, which diminishes PTH release and augments renal calcium excretion. The patient was started on cinacalcet and titrated up to 60mg daily. Calcium improved to 11.3 and she reported resolution of her headache, constipation and nausea as well as increased energy.
This is the first case describing a patient with symptomatic hypercalcemia due to FHH with CASR R185Q mutation treated with cinacalcet with improvement in hypercalcemia and symptoms.
Nothing to Disclose: DTB, AOP