A 46-year-old lady presented with left groin pain and was found to be hypercalcaemic. She admitted to lethargy and polydipsia but denied bone pain, depression, previous fractures or renal calculi. She denied thiazide or lithium use. There was a family history of primary hyperparathyroidism. Her paternal aunt remained persistently hypercalcaemic despite removal of a parathyroid adenoma. Subsequent selective venous sampling raised the possibility of an ectopic parathyroid gland. CASR gene mutation was negative. The patient’s father was also persistently hypercalcaemic despite subtotal parathyroidectomy. His parathyroid histopathology was consistent with hyperplasia.
At presentation she was adequately hydrated; neck and systemic examination were unremarkable. Corrected calcium was 3.30 mmol/L (2.15-2.55) and PTH 11.7 pmol/L (1.6-6.8). 24-hour urine calcium excretion was 9.3mmol/day (2.5-7.5), Urine calcium creatinine ratio was 0.018 (>0.01) indicating hypercalcuria. Renal function and hormonal investigations were normal. Bone mineral density and renal tract ultrasound were normal. Right inferior parathyroid adenoma was identified on ultrasound and sestamibi scans. Since the presentation was consistent with primary hyperparathyroidism she was referred for parathyroidectomy. Three enlarged parathyroid glands were removed during neck exploration. Histopathology revealed two adenomas and a normal parathyroid gland. Postoperatively, PTH levels normalized; calcium levels decreased to 2.78 mmol/L. A repeat sestamibi scan was normal. Due to persistent hypercalcaemia she was referred for CASR gene testing. Meanwhile, her father and aunt were reported positive for a new heterozygous R172T point mutation in CASR. Subsequently, this mutation was found in our patient. This indicates dual pathology namely Familial Hypocalcuric Hypercalcaemia (FHH) and Primary Hyperparathyroidism (PHPT).
Coexistence of FHH and PHPT is rare. It remains uncertain if CASR mutation plays a pathophysiological role in development of adenoma in FHH. It is important to identify this coexistence because removal of the adenoma can result in decrease in calcium levels to those characteristic of FHH.