Fellow University of South Florida wesley chapel, Florida, United States
Introduction : Familial Hypocalciuric hypercalcemia (FHH) is a rare autosomal dominant condition that occurs due to a mutation in the calcium sensing receptor gene (CaSR) that leads to decreased receptor activity. Patients typically have mild hypercalcemia, hypocalciuria, hypermagnesemia and hypophosphatemia with normal or mildly elevated PTH.
Case(s) Description : A 38 -year-old male with unremarkable past medical history was referred to our clinic for evaluation of hypercalcemia. Patient was adopted with no knowledge of family history. Albumin corrected calcium level ranged from 10.5 to 11 mg/dL, with parathyroid hormone (PTH) levels of 75, 86, and 95 (normal < 72 pg/mL). He had normal vitamin D, phosphate, creatinine and magnesium. A 24-hour urinary calcium was 74 mg/24hr with a calcium creatine ratio of 0.003. Sestamibi scan showed a subtle area on the left lobe that represented a possible parathyroid adenoma. Real-time ultrasound showed polar vascularity on the left, posterior to the midpole compatible with a possible parathyroid adenoma.
Considering his young age, high calcium level, degree of PTH elevation, findings on sestamibi and sonogram, we decided on getting a surgical opinion. With interdisciplinary collaboration from surgery service, and before proceeding with surgery, genetic testing was sent in the context of the low urine calcium and Ca/Cr ratio pointing to the possibility of FHH. The result was positive for FHH type 1 gene.
Discussion : FHH is a rare condition inherited in an autosomal dominant pattern. Because our patient was adopted, we did not have the benefit of a family history to corroborate this inheritance pattern. The true prevalence of this condition is unknown, estimated to be in the range of 1 in 78,000 compared with primary hyperparathyroidism of 1 in 1,000. It is possible to miss FHH due to its subclinical nature and the similarities its biochemical profile shares with primary hyperparathyroidism. Patients are usually asymptomatic or have few symptoms associated with hypercalcemia. An important component of the evaluation is the 24-hour urine calcium panel that allows for calculation of the calcium/creatinine ratio. Although imaging in this case suggested localization, totality of lab findings were within the expected range seen in patients with FHH and thus surgery was not pursued. As such, in patients with urine Ca/Cr ratio less than 0.020 testing for mutation of the CaSR gene should be strongly considered.
