Introduction: Chronic hyposphosphataemia is caused by increased concentrations of fibroblast-growth factor 23 (FGF23), mostly attributed to inactivating mutations of the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene. Secondary or tertiary hyperparathyroidism (THP) constitutes a rare complication of the disease, partly attributed to chronic supplementation of phosphate salts.
Case presentation: A 31-year old woman was admitted to our department on occasion of hypercalcaemia and hypophosphataemia. Until admission, she was being treated with oral alphacalcidol (0.5 μg/day) and phosphate (5 g/day). Her paediatric history included severe gait disturbances, clubfoot, osteotomies of the tibia and tooth reconstructions, a cluster of signs and symptoms compatible with the diagnosis of rickets. Biochemical and hormonal assessment on admission showed mild hypercalcaemia [corrected serum total calcium concentrations: 10.9 mg/dl (normal range: 8.410.4 mg/dl)] and hypophosphataemia [serum phosphate concentrations: 1.8 mg/dl (normal range: 1.92.5)], with high parathyroid hormone (PTH) [721 pg/ml (normal range 1065)] and low 25-hydroxy-vitamin D levels [15 ng/ml (sufficiency defined as >30 ng/ml)]. Renal function was normal [estimated glomerular filtration rate (eGFR): 114.9 ml/min/1.73 m2], as were the 24-h urinary calcium concentrations [114 mg/24-h (normal range: 50300)]. The maximum tubular resorption of phosphorus factored for glomerular filtration rate (TmP/GFR) was estimated at 0.96 mmol/l (female range: 0.961.44) indicative of hypophosphataemia due to renal loss of phosphate. Bone mineral density was normal, whereas bilateral nephrocalcinosis was observed on renal ultrasonography. Neck ultrasound showed enlargement of the right (inferior and superior) and the left superior parathyroid glands. A sestamibi scintigraphy scan was indicative of a hyperfunctioning right inferior parathyroid gland and, therefore, the diagnosis of THP was set. Afterwards, a gradual increase in alphacalcidol dose (1.5 μg/day) and cinacalcet (60 mg/day) was added to the patients regimen. Two months later, she underwent an uneventful parathyroidectomy, including removal of three enlarged parathyroid glands. Histological diagnosis was consistent of multiple parathyroid adenomas. Post-operative PTH and calcium concentrations were within normal range and so far remain normal, during a follow-up of 18 months.
Conclusions: THP may rarely develop during the course of chronic hypophosphataemia and should be taken into consideration, when hypercalcaemia develops. Early recognition and successful management with either parathyroidectomy or cinacalcet are recommended. Nonetheless, optimal dosage of alphacalcidol and phosphate salts, minimizing treatment-related adverse effects, is the mainstay of treatment in these patients.
18 May 2019 - 21 May 2019