Endocrine Abstracts

Background: Familial Hypocalciuric Hypercalcaemia (FHH) is a rare, benign cause of hypercalcaemia that closely mimics primary hyperparathyroidism (PHPT). Distinguishing FHH from PHPT is essential, as PHPT is often managed with parathyroidectomy. Surgery offers no benefit in FHH and carries unnecessary risk. FHH is characterised by elevated serum calcium, normal/mildly raised parathyroid hormone (PTH), and low urinary calcium excretion. The calcium–creatinine clearance ratio (CCCR) is a key discriminator: values <0.01 strongly suggest FHH, >0.02 usually exclude it, and 0.01–0.02 are considered indeterminate and may prompt genetic testing. CCCR results may be artificially lowered by vitamin D deficiency, renal impairment and medications, potentially leading to unnecessary genetic testing. Genetic testing is definitive but costly and inappropriate referrals burden NHS resources.

Methods: We retrospectively reviewed 35 patients referred for FHH genetic testing over a 4-year period. Data included serum calcium, PTH, CCCR, vitamin D, renal function, medication, family history, and genetic testing outcomes.

Results: CCCR values were available for 32 patients: <0.01 (n = 16), 0.01–0.02 (n = 10), >0.02 (n = 6). All 3 confirmed FHH cases had CCCR <0.01. All patients with CCCR ≥0.01 tested negative, giving an NPV of 100%. The PPV of CCCR <0.01 was 19% (3/16). Within the <0.01 group, 8/16 (50%) had vitamin D deficiency or confounding medication. Within the 0.01–0.02 group, 6/10 (60%) had confounders; all tested negative. 6 patients with CCCR >0.02 were inappropriately referred.

Conclusion: All FHH cases were identified by CCCR <0.01, while no positives were seen in higher ranges, supporting its use as a reliable rule-out test. Addressing confounders before referral could have reduced genetic testing by at least 54% (19/35 patients) without missing any true cases, with further reductions possible if <0.01 patients with confounders were re-evaluated. This would improve appropriateness of testing, deliver cost savings, and maintain safe investigation of hypercalcaemia.