Endocrine Abstracts

Familial hypocalciuric hypercalcaemia (FHH) usually manifests with mild asymptomatic hypercalcaemia. Presentations with severe hypercalcaemia are uncommon and may be mistakenly assumed to be primary hyperparathyroidism (PHPT) unless detailed testing is undertaken on all cases of hypercalcaemia. We present 4 cases of FHH presenting with severe hypercalcalcaemia, corrected serum calcium (coCalcium) > 3 mmol/l. Three cases were initially admitted to hospital as medical emergencies. 2 cases were initially misdiagnosed as primary hyperparathyroidism and underwent 3.5 gland parathyroidectomy.

Case 1: 40 year old lady, initial coCalcium 3.5. Diagnosed as PHPT. Underwent 3.5 gland parathyroidectomy. Subsequent persistent hypercalcaemia around 3. Histology of all surgical specimens was parathyroid hyperplasia, no adenoma. Further investigations suggested FHH. Genetic testing confirmed homozygous FHH1: calcium sensing gene mutation. Normal kidney function, normal bone density scan and renal ultrasound.

Case 2: 50 year old man, initial CoCalcium around 3.5. Diagnosed as PHPT. Underwent 3.5 gland parathyroidectomy. Subsequent persistent hypercalcaemia around 2.75. Histology of all surgical specimens was parathyroid hyperplasia, no adenoma. Further investigations suggested FHH. Genetic testing: heterozygous FHH1: calcium sensing gene mutation. Normal kidney function, normal bone density scan and renal ultrasound.

Cases 3 and 4: 63 year old man and his 37 year old son. Both presented with initial CoCalcium 3.1–3.2. Investigations showed low urine calcium excretion in father but not son. Genetic testing showed FHH3 due to adaptor protein 2 sigma subunit (AP2S) mutations in both.

Conclusion: Severe hypercalcaemia should not be assumed to be due to PHPT. All cases should have detailed investigation including calculation of the calcium to creatinine clearance ratio on a 24 h urine collection. If there is any diagnostic uncertainty then available first degree relatives should be screened for hypercalcaemia and molecular genetic testing performed. Homozygous FHH may present in adult life. FHH3 more frequently causes severe hypercalcaemia.