Endocrine Abstracts

Introduction: Hypercalcaemia is a relatively common medical condition affecting around 1% of the general population. Around 90% of the cases are due to either primary hyperparathyroidism (PHPT) or malignancy. Familial hypocalciuric hypercalcaemia (fHH) is a rare autosomal dominant condition that can result in hypercalcaemia. It has an estimated prevalence of1 in 78 000. In most of the cases, fHH is due to a mutation in the calcium-sensing receptor gene (CaSR). Other rare cases of fHH (fHH2 and fHH3) are due to mutations in the GNA11 gene and AP2S1 gene respectively. Very rarely, it can be caused by autoantibodies directed against the CaSR. Differentiating between fHH and PHPT can be difficult in the absence of family history. Normal PTH levels and low Calcium/Creatinine clearance ratio (< 0.01) are in favour of fHH. Resection of the parathyroid tissue might not lead to normalisation of the serum calcium level in fHH. Therefore, reaching an accurate diagnosis is crucial. Herein, we present a patient with hypercalcemia, normal PTH and low urinary Ca:Cr clearance ratio (UCCCR) in the absence of family history and with normal genetic testing. The presence of autoimmune hypocalciuric hypercalcaemia (AHH) was therefore suspected and confirmed. Due to the rarity of the condition, only a few cases have been reported.

Case Report: A 49-year-old lady was referred to the endocrinologist with hypercalcaemia and normal parathyroid hormone. She was symptomatic with fatigue and tiredness. She had a history of kidney stones. Her DEXA scan showed mild degree of osteopaenia. She was thoroughly investigated locally. Her tests showed very low UCCCR (<0.001) on 3 occasions and low 24-hour urinary calcium. An ultrasound scan and SESTAMIBI scan failed to localise any parathyroid abnormality. Genetic testing was negative for CaSR, GNA11 or AP2S1 gene defects. She was considered for exploratory surgery as possible PHPT. She was then referred to us for a second opinion. A repeat urine calcium was very low and she was found to suffer from mild autoimmune hypothyroidism. This raised the possibility of AHH. Anti-parathyroid antibodies were found to be positive. The patient was started on Cinecalcet which has helped reducing her calcium level and improving her symptoms.

Conclusion: This case demonstrates the diagnostic dilemma in hypercalcaemia that may lead a patient to undergo unnecessary invasive surgery. AHH should be suspected in patients with no clear surgical target and low urine CCCR if the genetic testing is negative.