Hereditary Hypophosphataemic Rickets with Tertiary Hyperparathyroidism (tHPT) - A Rare Differential Diagnosis for Severe Hypercalcaemia - Is There a Therapeutic Use for Cinacalcet?

Backround: Hereditary hypophosphataemic rickets is characterised by renal phosphate wasting as a result of elevated FGF23 (fibroblast growth factor) levels with reduced expression of proximal tubular sodium phospate co-transporters (NPT2). Additionally FGF23 decreases vitamin D levels by inhibiting calcitriol synthesis and stimulating degradation. The appropriate therapy for prevention of osteomalacia and growth retardation in childhood consists of calcitriol and phosphate substitution. Case Report: We report the case of a 53-year-old woman with the diagnosis of hypophosphataemic rickets presenting with severe hypercalcaemia (3.85 mmol/l) and renal insufficiency with nephrocalcinosis. After oral substitution of calcitriol (1 mu g/d) and phosphate (6.75 g/d) for 19 years, the serum phosphate level was 5 mg/dl while the calcitriol level was normal (24 pg/ml) and intact parathormone (iPTH) was elevated to 331 pg/ml (normal in 1990). This proved a tHPT while the parathyroid glands were enlarged on sonographic examination. Because the hypercalcaemia could not be controlled by conservative therapy, surgical parathyroidectomy had to be undertaken. After a postoperative decrease of iPTH, the levels increased again after a while. This could be successfully treated by "off label" use of the calcimimetic drug cinacalcet. Discussion: The excessive phospate substitution resulted in hyperhposphataemia, aggravated by phophate retention caused by the renal insufficiency. The decrease of ionised serum calcium by formation of calcium phophate complexes and the reduced calcitriol levels could have caused a continuing stimulation of the parathyroid glands leading to the development of a secondary hyperparathyroidism (sHPT) proceeding to a tHPT with hypercalcaemia. By intensified stimulation of the parathyroid gland's calcium receptors, cinacalcet could decrease parathormone secretion. Conclusions: During vitamin D and phophate substitution therapy for hypophosphataemic rickets, serum phosphate, serum and urine calcium, creatinine and iPTH should be monitored at close intervals. This is essential to detect complications like renal insufficiency with nephrocalcinosis and the severe hypercalcaemia early enough to change the therapeutic strategy by a change of medication dosage or even to surgical intervention. Our case report demonstrates the decreasing effect of the calcimimetic cinacalect on the iPTH level in a patient with hypophosphataemic rickets as a useful alternative to surgical intervention.