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7. Uniparental disomy and pretreatment IGF-1 may predict elevated IGF-1 levels in Prader-Willi patients on GH treatment

Author

Malgorzata Wasniewska, Maria Chiara Pellegrin, Rita Fischetto, Francesca Macchi, Antonella Lonero, Sara Osimani, A. Crinò, Adriana Franzese, Sarah Bocchini, Gilda Cassano, Luana Nosetti, Annamaria Perri, Giuseppa Patti, Maria Rosaria Licenziati, Michele Sacco, Stefano Stagi, Alessandro Salvatoni, G. Trifirò, Rosanna Lia, Simona Filomena Madeo, Irene Rutigliano, Lorenzo Iughetti, Paola Giordano, Danilo Fintini, Gianluca Tornese, Alessio Convertino, Patrizia Matarazzo, Graziano Grugni, S. Ferraris, Emanuela Scarano, Domenico Corica, Valentina Fattorusso, Viviana Valeria Palmieri, Roberta Pajno, L. Ragusa, Maurizio Delvecchio, Palmieri, V. V., Lonero, A., Bocchini, S., Cassano, G., Convertino, A., Corica, D., Crino, A., Fattorusso, V., Ferraris, S., Fintini, D., Franzese, A., Grugni, G., Iughetti, L., Lia, R., Macchi, F., Madeo, S. F., Matarazzo, P., Nosetti, L., Osimani, S., Pajno, R., Patti, G., Pellegrin, M. C., Perri, A., Ragusa, L., Rutigliano, I., Sacco, M., Salvatoni, A., Scarano, E., Stagi, S., Tornese, G., Trifiro, G., Wasniewska, M., Fischetto, R., Giordano, P., Licenziati, M. R., and Delvecchio, M.

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Growth hormone therapy, 030209 endocrinology & metabolism, Adverse effect, Gastroenterology, Growth velocity, 03 medical and health sciences, Adverse effects, IGF-1, Prader-Willi syndrome, Uniparental disomy, Child, Child, Preschool, Female, Human Growth Hormone, Humans, Infant, Insulin-Like Growth Factor I, Prader-Willi Syndrome, Prognosis, Uniparental Disomy, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, Preschool, Normal range, business.industry, Human growth hormone, medicine.disease, Highly sensitive, 030104 developmental biology, Gh treatment, business
Abstract

Pediatric patients with Prader-Willi syndrome (PWS) can be treated with recombinant human GH (rhGH). These patients are highly sensitive to rhGH and the standard doses suggested by the international guidelines often result in IGF-1 above the normal range. We aimed to evaluate 1 the proper rhGH dose to optimize auxological outcomes and to avoid potential overtreatment, and 2 which patients are more sensitive to rhGH. In this multicenter real-life study, we recruited 215 patients with PWS older than 1 year, on rhGH at least for 6 months, from Italian Centers for PWS care. We collected auxological parameters, rhGH dose, IGF-1 at recruitment and (when available) at start of treatment. The rhGH dose was 4.3 (0.7/8.4) mg/m2/week. At recruitment, IGF-1 was normal in 72.1% and elevated in 27.9% of the patients. In the group of 115 patients with IGF-1 available at start of rhGH, normal pretreatment IGF-1 and uniparental disomy were associated with elevated IGF-1 during the therapy. No difference in height and growth velocity was found between patients treated with the highest and the lowest range dose. The rhGH dose prescribed in Italy seems lower than the recommended one. Normal pretreatment IGF-1 and uniparental disomy are risk factors for elevated IGF-1. The latter seems to be associated with higher sensitivity to GH. In case of these risk factors, we recommend a more accurate titration of the dose to avoid overtreatment and its potential side effects.

Published
2019

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