A 22-year-old woman with hypophosphataemic rickets was diagnosed at age four when she presented with short stature and valgus deformity of the lower limbs. Biochemical testing, genetic screening and radiological investigation of her family showed no abnormality and it was concluded that she had a de novo mutation.
She was treated with 1α-calcidol and phosphate Sandoz with regularly monitored biochemistry. She had poor adherence to her medication and her phosphate levels fluctuated. Her valgus deformity showed little improvement and she required stapling of her left distal medial epiphyseal plate at age 15 years.
At age 14 she had been diagnosed with secondary hyperparathyroidism with calcium 2.38 mmol/l, phosphate 0.91 mmol/l and parathyroid hormone (PTH) 24.71 pmol/l. Her renal function was normal. The need to adhere to 1α-calcidol was reiterated, but her PTH remained elevated. At age 18 she developed hypercalcaemia with calcium 3.19 mmol/l, phosphate 1.61 mmol/l and PTH 10.3 pmol/l and her 1α-calcidol was gradually reduced to 500 μg once a week. Despite this her calcium remained elevated at 2.85 mmol/l with a progressively increasing PTH (65.4 pmol/l) confirming a diagnosis of tertiary hyperparathyroidism. She had a sestamibi scan which identified bilateral lower pole parathyroid adenomas, for which she declined surgery and was therefore treated with cinacalcet, starting at 30 mg daily and increased to 90 mg daily in divided doses. The calcium and PTH decreased to 2.58 mmol/l and 23.4 pmol/l respectively over a period of 8 months. β-CTX a marker of bone resorption was normal at 0.3 μg/l (NR 0.10.5).
Although cinacalcet is unlicensed for treatment of tertiary hyperparathyroidism, this case demonstrates the effective use of cinacalcet in lowering PTH and calcium in tertiary hyperparathyroidism in hypophosphataemic rickets. The normal β-CTX concentration would also suggest that there is benefit at the target organ, bone, by maintaining normal bone resorption which would otherwise be high in hyperparathyroidism.