Endocrine Abstracts

Case History: 16-year-old fit and well lady was referred to endocrinology clinic by GP due to severe hypercalcaemia. She is being investigated for secondary amenorrhea. She is not taking any regular medication. There is a history of hypercalcaemia in the family, her mother has hypercalcaemia and paternal grandfather had hypercalcaemia. She had no signs and symptoms of hypercalcaemia.

Investigations: Corrected Calcium: 3.28 mmol/l, Phosphate: 0.60 mmol/l, 25 OH vitamin D: 28 nmol/l, Cortisol: 225 nmol/l. Normal Synacthen test, Parathyroid hormone: 4.1 pmol/L, Normal Gut Hormone profile. Normal Prolactin, Ultrasound Parathyroid is normal. Parathyroid MIBI scan is normal, Ultrasound of abdomen showed no urolithiasis

Results and treatment: IV Fluid and IV Pamidronate were given and repeat calcium after treatment was 2.73 mmol/l. However, follow-up blood showed that she had persistent hypercalcaemia (>3 mmol/l). Therefore, PO Cinacalcet was given but she is not taking regularly. As a result, her calcium level is persistently above 3 mmol/l. We tried multiple attempt to do 24-hour urinary calcium/creatinine clearance, but patient did not give the sample. However, just recently she provided 24-hour urine sample which showed 24-hour urine calcium level 0.9 mmol/l and 24-hour urinary calcium: creatine ratio 0.011 mmol/mmol. Because of strong family history of hypercalcaemia and patient has hypercalcaemia with biochemical test suggestive of neonatal hyperparathyroidism, genetic test was requested which showed heterozygous sequence change in calcium sensing receptor gene C.554G>A, p.(Arg185Gln). Her mother was also seen in our endocrinology clinic and diagnosed as Familial hypocalciuric hypercalcemia (FHH) which is evidenced by hypercalcaemia (>3 mmol/l) and hypocalciuria (24 hr Urinary Calcium is 2.6 mmol/24 hr and calcium creatinine clearance ratio is 0.006 mmol/mmol). She also had same mutation as her daughter and her USG Neck and Parathyroid MIBI scan were normal.

Conclusion and points for discussion: Patient’s 24-hour urinary calcium: creatine ration is borderline to diagnose familial hypocalciuric hypercalcemia. Calcium level of both patient and her mother is higher than expected in familial hypocalciuric hypercalcemia. Same genetic mutation found in both patient and her mother are associated with neonatal hyperparathyroidism. We advised to continue with oral hydration and cinacalcet 60 mg BD. In this rare mutation in calcium sensing receptor gene, should we observe calcium level, or should we consider parathyroidectomy?