Abstract #1408170: Familial Hypocalciuric Hypercalcemia, Primary Hyperparathyroidism, or Both?

Abstract

Primary hyperparathyroidism (PHPT) is the leading cause of hypercalcemia, and it is characterized by hypercalcemia and normal or inappropriately high levels of parathyroid hormone (PTH). Familial Hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant benign disease caused by inactivating genetic mutations in the calcium sensing receptor. Genetic analyses are expensive and not widely available, making the differential diagnosis challenging. A 77-year-old male with a past medical history of hypertension and chronic kidney disease was referred to the endocrinology clinic for evaluation of hypercalcemia. Routine tests showed total corrected calcium level of 10.5 mg/dL, hypophosphatemia 2.6 mg/dL and low 24h urinary calcium of 79 mg/24h with calcium creatinine clearance ratio (CCCR) of 0.008. 25 hydroxyvitamin D, 1,25 Dihydroxyvitamin D and magnesium were normal. PTH level was 33 pg/dL (normal 15-65 pg/dL). Patient had no hypercalcemic symptoms, history of nephrolithiasis, or bone fractures. No family history of hypercalcemia. Cancer screening and PTH related peptide were normal. He was not taking hydrochlorothiazide or lithium. Renal ultrasound showed no nephrolithiasis and DXA revealed no osteoporosis. Thyroid ultrasound showed a right 1.2cm thyroid nodule without visualization of parathyroid glands. Fine-needle aspiration biopsy (FNA) of the nodule with PTH washout was benign with PTH<10. The patient was diagnosed with FHH and was monitored semiannually. Four years after the initial evaluation, total corrected calcium level was elevated at 14 mg/dL with PTH of 378 despite 25 hydroxyvitamin D level >40, repeated urinary calcium 90 mg/24h, and CCCR 0.01. His renal function was unchanged. Parathyroid scintigraphy revealed increased uptake in the right upper thyroid lobe, and thyroid ultrasound revealed increased right thyroid nodule volume. Repeat FNA was benign, this time with a PTH washout >200. The patient opted against surgical consultation for parathyroidectomy. He was treated with cinacalcet 30 mg twice daily. The co-existence of FHH and PHPT is rare. The few reported cases include patients who maintained hypercalcemia after surgical treatment of PHPT. The best cost-effective test available is a CCCR < 0.02. Our patient had CCCR measured at different times with values < 0.01 and a PTH level that over time increased by 900%. The overlap of biochemical values in patients with FHH and PHPT contributes to the challenges in the differential diagnosis and highlights the importance of close follow up with a high degree of clinical suspicion.