1 Department of Clinical, Internal, Anaesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.
2 Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Japan.
3 Department of Endocrinology, Key Laboratory of Endocrinology of National Commission of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College. Beijing 100730, China.
4 Department of Molecular Medicine, Sapienza University of Rome, Italy.
5 Unità Operativa di Endocrinologia Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-“Casa Sollievo della Sofferenza”-Hospital, San Giovanni Rotondo, Foggia, Italy.
6 Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill Hospital, Headington, Oxford OX3 7LJ, UK.
Tumor-induced osteomalacia (TIO) is an ultrarare paraneoplastic syndrome due to overproduction of fibroblast growth factor 23 (FGF23), with profound effects on the morbidity of the patients affected. TIO is an underdiagnosed disease, whose awareness should be increased among physicians, for timely and proper management of the patients. Symptoms reported by patients with TIO are usually nonspecific thus rendering the diagnosis elusive, with an initial misdiagnosis rate of >95%. Biochemical features of TIO are represented by hypophosphatemia, increased or inappropriately normal levels of FGF23 and low to low normal circulating 1,25(OH)2D. Phosphaturic mesenchymal tumors are the pathological entities underlying TIO in most affected patients. There is now evidence that FN1-FGFR1 and FN1-FGF1 fusion genes are present in about half of tumors causing this paraneoplastic syndrome. Tumors causing TIO are often of small size and grow slowly. They can occur in all parts of the body from head to toe with similar prevalence in soft tissue and bone. There are a number of functional and anatomical imaging techniques utilized for tumor localization; 68Ga DOTA based technologies have the better sensitivity. Surgery is the treatment of choice; several medical treatments are now available in case of inability to locate the tumor or in case of incomplete excision.