Tertiary hyperparathyroidism in a patient with X-linked hypophosphatemic rickets.

A 29-year-old female (Weight=50 kg, Height=152 cm, Body Mass Index= 21.6 Kg/m, target height: 151.5 cm) with symptomatic XLHR (X-linked Hypophosphatemic Rickets) since childhood was referred for evaluation of hypercalcemia. At the age of three years, during evaluation for growth retardation and features of rickets along with hypophosphatemia, she received the diagnosis of XLHR. Family history was negative for XLHR. Treatment consisted of oral phosphate salts and alfacalcidol, therapy that was continued until the age of 18 yrs. After the age of eighteen years she received intermittently alfacalcidol without phosphate salts. The following ten years before current evaluation she developed nephrocalcinosis diagnosed by ultrasound and renal computed tomography (Figure 1a,b). By that time she reported progressive increase in serum calcium levels. At presentation, while off alphacalcidol treatment for at least 3 months, she reported weakness and generalized muscle pain, symptoms suggestive of osteomalacia. There was no history of fractures, while no deformities were detected. Laboratory examinations were compatible with tertiary hyperparathyroidism (Table 1). Bone mineral density (BMD) measurements by Dual X-ray Absorptiometry (DXA) at the lumbar spine and hip were within normal range. The patient underwent genetic testing for PHEX mutations which revealed a new mutation/variation at the 6 nucleotide downstream of the coding exon 14: c.1586+6T>A. Prediction programs predicted that this variation will have an effect on correct RNA splicing (Jongbloed J.D.H., PhD, Department of Genetics, UMCG, Groningen, the Netherlands). Neck ultrasound showed enlargement of the two inferior parathyroid glands (right 21*9 mm and left 10*6 mm), while parathyroid imaging with Tcsestamibi scintigraphy revealed a hyperfunctioning right inferior parathyroid gland. In order to improve the vitamin D and phosphate deficit prior to surgical intervention, the patient was treated with cinacalcet 30 mg b.i.d. (twice a day) for 2 weeks, followed by addition of alphacalcidol 0.5 μg q.d. (once a day) and phosphate 500 mg q.i.d. (four times a day) with excellent results. There was normalization in serum calcium levels, increase in phosphate levels, while parathyroid hormone (PTH) levels decreased significantly, to almost normal levels. Two months later the patient underwent bilateral cervical exploration. All four parathyroid glands were identified and subtotal parathyroidectomy was performed. Histological examination revealed diffuse chief-cell hyperplasia with compact, trabecular and/ or follicular growth pattern (Figure 1c,d). In the immediate post-operative period the patient was treated with oral calcium [500 mg t.i.d. (three times a day)] and alphacalcidol (1.5 μg q.d). Progressively calcium adminJ Musculoskelet Neuronal Interact 2011; 11(3):266-269