A 46-year-old Columbian man, with a previous history of pulmonary sarcoid and renal calculi in 2001, was referred to the Endocrinology clinic in 2005 with persistent hypercalcaemia despite successful treatment of the sarcoid. The initial hypercalcaemia work-up results were as follows: adjusted calcium 2.96 (2.152.60), parathyroid hormone (PTH) 9.0 pmol/l (1.16.8), 25-(OH)2 vitamin D 71 nmol/l (>50), magnesium 0.99mmol/l (0.651.00), creatinine 97 umol/l (60125), 24 hour urinary calcium 2.30 mmol/l and calcium/creatinine clearance ratio (CCCR) 0.0026. The results suggested a picture of FHH, but given the marked elevation of calcium, previous history of renal calculi and lack of family history, further investigations to explore the possibility of primary hyperparathyroidism (PHPT) were performed. Repeat 24 hour CCCR was less than 0.01. An ultrasound and sestamibi scan did not detect a parathyroid adenoma. The renal ultrasound, a hand X-ray and dexa bone scan were normal. A hydrocortisone suppression test did not show suppression of calcium after 5 days, suggesting that the hypercalcaemia was not due to continued activity of the sarcoid. Serum ACE levels remained in the normal range. Genetic analysis for FHH showed an R220W mutation, which has been previously demonstrated to cause a right shift in the dose response curve to extracellular calcium.
Discussion: FHH is a genetic condition caused by inactivating mutations in the calcium sensing receptor (CASR) gene on chromosome 3. Its inheritance is autosomal dominant. The biochemical picture normally consists of mild hypercalcaemia, normal-elevated PTH, normal vitamin D and hypocalciuria. Symptoms and end-organ damage, due to hypercalcaemia, in FHH are generally absent. However, acute pancreatitis, chondrocalcinosis and renal calculi have been reported. Our case highlights the importance of considering the diagnosis of FHH even in the presence of end-organ damage related to hypercalcaemia. It is important to separate this condition from PHPT, to avoid unnecessary surgery.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.