Coexistence of a Calcium-Sensing Receptor Mutation and Primary Hyperparathyroidism

Abstract

Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the main differential diagnoses in a patient presenting with parathyroid hormone (PTH)-mediated hypercalcemia. PHPT is most often caused by a single-gland parathyroid adenoma and FHH is the result of an inactivating mutation of the calcium-sensing receptor (CaSR) gene.In this paper, we present a unique case of the co-existence of an inactivating CaSR gene mutation and PHPT due to a single-gland parathyroid adenoma. The patient is a 67-year-old female with a history of recurrent nephrolithiasis who presented with hypercalcemia, elevated PTH level, and hypocalciuria. As a result of the patient's hypocalciuria, familial hypocalciuric hypercalcemia was suspected, and genetic testing was pursued. CaSR gene analysis revealed a heterogeneous inactivating mutation of the CaSR gene. Additionally, nuclear imaging with technetium sestamibi revealed a large focus of activity on the right side of the neck suspicious of a parathyroid adenoma. This was resected and confirmed to be a hypercellular parathyroid adenoma. Two years after her surgery, the patient continues to have normal calcium levels with no further episodes of nephrolithiasis. She is currently undergoing treatment for osteoporosis and is being periodically monitored for recurrence of hypercalcemia due to the presence of the inactivating CaSR gene mutation. This case highlights an exceedingly rare case of a patient with both an inactivating CaSR gene mutation and PHPT due to a single parathyroid adenoma, and it underscores the importance of further research to determine any potential relationship between the two.