Distinguishing between primary hyperparathyroidism and familial hypocalciuric hypercalcaemia-the role of genetic testing in patient with equivocal results.

Ling Y, Falinska A, Vakilgilani T, Tanday R, Todd JF

Imperial College Healthcare NHS Trust.


A 64 year old gentleman was referred with persistent hypercalcaemia following two previous parathyroidectomies from an external hospital. He was found to be hypercalcaemic incidentally by his GP in 2011. Prior to surgery in January 2011, his corrected calcium (cCa) was 2.83 mmol/l, PTH 1.9pmol/l, vitamin D 38nmol/l, 24hour urine calcium creatinine clearance ratio (24hr UCCR) was 0.0135. Histology from his 1st neck exploration revealed one hyperplastic parathyroid gland. A further parathyroid gland (hyperplastic), two lymph nodes and a thymic remnant was resected in the 2012 for recurrent primary hyperparathyroidism (PHPT).


He presented in 2013 with generalised lethargy with cCa 2.89mmol/l, PTH 4.1 pmol/l, vitamin D 58.1nmol/l, 24hr UCCR 0.0148. A repeat 24hr UCCR was 0.0065 (vitamin D 85.4nmol/l). He was osteopenic and had no nephrocalcinosis. USS parathyroids and SESTAMIBI did not demonstrate any suspicion of parathyroid adenoma. CT neck also did not show any parathyroid adenoma.


From these investigations, it is possible that he has familial hypocalciuric hypercalcaemia (FHH) in view of the recurrent hypercalcaemia, histological findings and equivocal 24hr UCCR.  His genetic screen for calcium sensing receptor (CASR) gene mutation is awaited.


This case illustrates the challenges of diagnosing PHPT versus FHH especially in patients with equivocal results. None of the investigations can differentiate between the two with absolute certainty.


Distinguishing between PHPT and FHH has traditionally relied upon 24hr UCCR.  A 24hr UCCR of <0.01 suggests FHH (85% sensitivity 88% specificity) whilst >0.02 was typical of PHPT. However 24hr UCCR between 0.01 to 0.02 is a grey area.


CASR gene mutation is detected in up to 80% of patients with FHH. Although genetic analysis is still not recommended for routine evaluation of PHPT, it can be very useful in patients who have equivocal 24hr UCCR in whom FHH is suspected to avoid unnecessary surgical intervention.