ESPE2021 ePoster Category 1 Pituitary B (10 abstracts)
Puberty and pituitary-gonadal axis function after treatment for a childhood brain tumor
Manon Rosimont 1,2 , Dulanjalee Kariyawasam 1 , Dinane Samara-Boustani 1 , Elisa Giani 1 , Jacques Beltrand 1,3 , Stéphanie Bolle 4 , Brice Fresneau 5 , Stéphanie Puget 3,6 , Christian Sainte-Rose 6 , Claire Alapetite 7 , Graziella Pinto 1 , Marie-Liesse Piketty 8 , Séverine Brabant 8 , Samuel Abbou 9 , Isabelle Aerts 10 , Kevin Beccaria 6 , Marie Bourgeois 6 , Thomas Roujeau 11 , Thomas Blauwblomme 6 , Frederico Di Rocco 12 , Caroline Thalassinos 1 , Michel Zerah 6 , Christian Pauwels 1 , Charlotte Rigaud 9 , Syril James 6 , Kanetee Busiah 13 , Albanne Simon 14 , Franck Bourdeaut 10 , Lauriane Lemelle 10 , Léa Guerrini-Rousseau 9 , Daniel Orbach 10,15 , Philippe Touraine 16 , François Doz 3,10 , Christelle Dufour 9 , Jacques Grill 9 , Michel Polak 1,3 & Laura G. González Briceño 1,17
1Hôpital Universitaire Necker-Enfants Malades - Assistance Publique Hôpitaux de Paris (APHP), Service d’Endocrinologie, Gynécologie et Diabétologie Pédiatrique, Institut IMAGINE (affiliate), Paris, France; 2Université de Liège, Médecin Spécialiste en 5ème Année de Formation de Pédiatrie, Liège, Belgium; 3Université de Paris, Paris, France; 4Institut Gustave Roussy, Département de Radiothérapie-Oncologie, Villejuif, France; 5Gustave Roussy, Université Paris-Saclay, Department of Pediatric Oncology, Villejuif, France; 6Hôpital Universitaire Necker-Enfants Malades - APHP, Service Neurochirurgie, Paris, France; 7Institut Curie, Radiation Oncology Department and Proton Center, Paris, France; 8Hôpital Necker Enfants Malades, Explorations Fonctionnelles, Paris, France; 9Gustave Roussy, Université Paris-Saclay, Department of Pediatric Oncology, Paris, France; 10Institut Curie, SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), Paris, France; 11Hôpital Montpellier, Hôpital Gui de Chauliac, Unité de Neurochirurgie pédiatrique, Montpellier, France; 12Hôpital Lyon-Bron, Service Neurochirurgie, Lyon, France; 13Lausanne University Hospital, Pediatric Endocrinology, Diabetology and Obesity Unit, Lausanne University, Lausanne, Switzerland; 14Hôpital André Mignot, Le Chesnay, Endocrinologie Pédiatrique, Le Chesnay-Rocquencourt, France; 15PSL Research University, Paris, France; 16Hôpital Universitaire La Pitié-Salpêtrière - APHP, Service Endocrinologie et Médecine de la Reproduction, Sorbonne Université Médecine, Paris, France; 17ESPE Fellowship, Paris, France
Introduction: Primary brain tumors are the second most common childhood malignancies, with an increasing survival rate over the years. Late effects on puberty and fertility alter survivors’ quality of life.
Methods: We included 204 patients diagnosed with a primary brain tumor before 18 years, followed in pediatric endocrinology at the University Hospital “Necker-Enfants Malades” in Paris between January 2010 and December 2015. Data was retrieved from medical records to analyze pubertal timing and the effects of the tumor and its treatments.
Results: The total cohort of 204 patients was studied for early puberty (EP) and gonadal toxicity (GT), and 187 patients (≥13 years (girls) or ≥14 years (boys) were analyzed for hypogonadotropic hypogonadism (HH). Among these 187 patients, only 53 (28.3%) had spontaneous puberty at the same time as their peers, with no significant sex ratio. Of 32 patients with a suprasellar glioma, 19 had EP, with a positive predictive value (PPV): 59.4%, P = 0.001. Risk for EP was lower when radiotherapy dose was high, >40 Gy (n = 2/6, PPV: 33.3%, P = 0.02), and it increased with doses <40 Gy or when the child had not been treated by radiotherapy (n = 17/26, PPV: 65.4%). There was a trend for higher PPV for EP in younger children (diagnosis <5 years), but this was not statistically significant. Thirty out of 43 patients with medulloblastoma treated by high-risk chemotherapy developed GT on average 7.6±3.7 years after the end of treatment (PPV=69.7%, P = 0.001); patients who were not treated by chemotherapy (n = 17) did not develop GT (PPV: 0%, P = 0.001). Children diagnosed <5 years of age had a higher risk of GT after chemotherapy (n = 14/16, PPV=87.5%, P = 0.001). Craniopharyngioma was associated with an increased risk of HH regardless of treatment (n = 39/56, PPV 69.6%, P = 0.001). Growth hormone deficiency (GHD) increased the risk of HH to 79.2%, whereas in absence of GHD, the PPV was 0% (P = 0.001).
Conclusions: The type of tumor, its location and treatment are the main factors that drive the type of pituitary-gonadal axis dysfunction. Craniopharyngioma is associated with a risk of HH, glioma with EP and medulloblastoma (through high-risk chemotherapy) with GT. Awareness of potential secondary effects and their mechanism is essential to assess pubertal status of these patients, to guide parental information, and to decide of an adequate and timely hormone replacement therapy.
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