Introduction: We present an unusual case of hypophosphataemia with diagnostic dilemma.
Case: 43-year-old female presented with 4-year history of muscle weakness, fatigue, bony pains, and limb paraesthesia. There was no background of fractures or iron deficiency. Her medications included amitriptyline and probiotics. She was a non-smoker and teetotaller; mother was short stature, father normal height. There was no family history of fractures or rickets. On assessment, height-169cm, weight-91.8 kg, BMI 32 kg/m2, normal physical examination, no features suggestive of Fanconis syndrome. Phosphate (PO4) was low 0.37mmol/l (0.8-1.5), vitamin D 28.3 nmol/l (>50) with normal calcium, magnesium, parathyroid hormone, renal function and TSH. 24hr urinary PO4 102.8mmol (15-50), fractional excretion of filtered PO4 60.4% (5-20), high fibroblast growth factor-23 (FGF-23) 115RU/ml (<100), 1,25-dihydroxy vitamin D 179 pmol/l (20-120), normal short synacthen test; genetic analysis negative. FDG-CT PET suggested metabolically inactive left ovarian cyst, transvaginal ultrasound revealed simple cyst which disappeared on repeat ultrasound. Tumour markers (AFP, CEA, CA-125, beta-HCG, LDH), gastrointestinal malabsorption tests were negative. Oral phosphate replacement with cholecalciferol commenced, despite which the phosphate levels were low, later changed to alfacalcidol. Phosphate remained low (0.3-0.9mmol/l), limited by hypercalcemia on increasing dose of alfacalcidol.
Discussion: Chronic hypophosphatemia results in childhood rickets, osteomalacia, and skeletal muscle myopathy. Severe hypophosphatemia (<0.32mmol/l) causes arrhythmias, rhabdomyolysis, acute haemolytic anaemia. FGF-23, produced by osteocytes/osteoblasts reduces intestinal absorption of serum phosphate by decreasing 1,25-dihydroxy vitamin D and restricting proximal tubular phosphate reabsorption. FGF-23 mediates hypophosphataemic disorders, both hereditary (X-linked hypophosphatemia-XLH) and acquired (tumour induced osteomalacia). Treatment is oral phosphate and active vitamin D with aim to achieve low-normal phosphate levels. Burosumab, a recombinant human IgG1 monoclonal antibody targeting FGF-23 is licenced for use in XLH.
Conclusion: Extensive investigations may fail to identify a cause for symptomatic phosphaturic hypophosphataemia and drug therapy may be suboptimal due to drug induced hypercalcemia.
13 Nov 2023 - 15 Nov 2023