Frédérique Albarel1, Caroline Gaudy2, Frédéric Castinetti1, Tiphaine Carré2, Isabelle Morange1, Bernard Conte-Devolx1, Jean-Jacques Grob2, Thierry Brue3. 1. Assistance Publique - Hôpitaux de Marseille (AP-HM)Hôpital Timone, Service d'Endocrinologie et Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéAssistance Publique - Hôpitaux de Marseille (AP-HM), Hôpital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hôpitaux de Marseille (AP-HM)Hôpital Timone, Service d'Endocrinologie et Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéAssistance Publique - Hôpitaux de Marseille (AP-HM), Hôpital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France. 2. Assistance Publique - Hôpitaux de Marseille (AP-HM)Hôpital Timone, Service d'Endocrinologie et Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéAssistance Publique - Hôpitaux de Marseille (AP-HM), Hôpital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France. 3. Assistance Publique - Hôpitaux de Marseille (AP-HM)Hôpital Timone, Service d'Endocrinologie et Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéAssistance Publique - Hôpitaux de Marseille (AP-HM), Hôpital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France Assistance Publique - Hôpitaux de Marseille (AP-HM)Hôpital Timone, Service d'Endocrinologie et Centre de Référence des Maladies Rares d'Origine Hypophysaire DEFHY, 13385 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéCNRS, CRN2M-UMR7286, 13344 Marseille Cedex 15, Marseille, FranceAix-Marseille UniversitéAssistance Publique - Hôpitaux de Marseille (AP-HM), Hôpital Timone, Service de dermatologie, 13385 Marseille Cedex 15, Marseille, France thierry.brue@univ-amu.fr.
Abstract
OBJECTIVE: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up. DESIGN AND PATIENTS: Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille. METHODS:Symptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded. RESULTS: Of 131 patients treated withipilimumab or a placebo, 15 patients (10 mg/kg in 11/15) presented with hypophysitis (≥11.5%) at 9.5±5.9 weeks (mean±s.d.) after treatment start, occurring in 66% after the third infusion. The main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7-53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and ten gonadotroph functions. Pituitary imaging remained abnormal in 11 patients. CONCLUSION:Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term.
RCT Entities:
OBJECTIVE: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs, endocrinological profile, and imaging at diagnosis and during a long-term follow-up. DESIGN AND PATIENTS: Fifteen patients, treated for malignant melanoma and who presented ipilimumab-induced hypophysitis, were observed between June 2006 and August 2012 in Timone Hospital, Marseille. METHODS: Symptoms, pituitary function, and pituitary imaging at diagnosis of hypophysitis and during the follow-up were recorded. RESULTS: Of 131 patients treated with ipilimumab or a placebo, 15 patients (10 mg/kg in 11/15) presented with hypophysitis (≥11.5%) at 9.5±5.9 weeks (mean±s.d.) after treatment start, occurring in 66% after the third infusion. The main initial symptoms were headache (n=13) and asthenia (n=11). All patients but one had at least one hormonal defect: thyrotroph (n=13), gonadotroph (n=12), or corticotroph (n=11) deficiencies. None had diabetes insipidus. Pituitary imaging showed a moderately enlarged gland in 12 patients. Clinical symptoms improved rapidly on high-dose glucocorticoids (n=11) or physiological replacement doses (n=4). At the end of follow-up (median 33.6 months, range 7-53.5), corticotroph deficiency remained in 13 patients, 11 recovered thyrotroph and ten gonadotroph functions. Pituitary imaging remained abnormal in 11 patients. CONCLUSION:Ipilimumab-induced hypophysitis is a common side-effect with frequent hormonal deficiencies at diagnosis. Usually, hormonal deficiencies improved, except for corticotroph function. Patients receiving these immunomodulatory therapies should be closely monitored especially by systematic baseline hormone measurements after the third infusion and remain at a risk of adrenal insufficiency in the long-term.
Authors: Allison J Pollock; Tasa S Seibert; Cristiana Salvatori; Patrizio Caturegli; David B Allen Journal: Horm Res Paediatr Date: 2016-06-30 Impact factor: 2.852
Authors: Jaydira Del Rivero; Lisa M Cordes; Joanna Klubo-Gwiezdzinska; Ravi A Madan; Lynnette K Nieman; James L Gulley Journal: Oncologist Date: 2019-10-10