Disorders of phosphate metabolism--pathomechanisms and management of hypophosphataemic disorders.
Hypophosphataemia does not necessarily indicate phosphate (Pi) depletion. In acute emergencies such as septicaemia, alkalosis or re-feeding, hypophosphataemia may result from redistribution of Pi from the extracellular to the intracellular space. Hypophosphataemia from true Pi depletion gives rise to skeletal (osteomalacia) and extraskeletal (myopathy, cardiomyopathy) disorders. It is practically never the result of diminished nutritional intake. The most severe syndromes of Pi depletion result from diminished tubular Pi re-absorption and renal Pi wasting. In the differential diagnosis mainly four conditions have to be considered: (i) tumour-associated osteomalacia, (ii) X-linked hypophosphataemia (XLH), (iii) autosomal dominant hypophosphataemia, and (iv) hypercalcaemic renal phosphate wasting. Recent molecular insight has put fibroblast growth factor (FGF-23) into the centre of pathophysiological considerations because of (i) overproduction (tumour-associated osteomalacia) or (ii) hypothetically, accumulation resulting from mutations causing resistance to processing or degradation (autosomal dominant hypophosphataemia) or (iii) loss-of-function of a protease (PHEX) interfering with FGF-23 breakdown (XLH). In oncogenic osteomalacia the treatment of choice is resection of the tumour. Recently, pharmacological treatment has also become possible, i.e. administration of octreotide. XLH and autosomal dominant hypophosphataemia must be managed by oral administration of phosphate and calcitriol. In patients with gastrointestinal intolerance to phosphate or with severely symptomatic bone disease, prolonged intravenous administration of Pi is necessary.
Ritz
Eberhard
E
Department of Internal Medicine, Ruperto Carola University, Bergheimer Str. 58, Heidelberg D-69115, Germany. prof.e.ritz@t-online.de
Haxsen
Volker
V
Zeier
Martin
M
D003937:Diagnosis, Differential; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D006934:Hypercalcemia / Q000150:complications / Q000175:diagnosis; D017674:Hypophosphatemia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D007015:Hypophosphatemia, Familial / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis; D010018:Osteomalacia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000628:therapy; D010710:Phosphates / Q000378:metabolism*; D011859:Radiography
C000717427:FGF23 protein, human; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23