title: Growth hormone treatment for childhood short stature and risk of stroke in early adulthood.
abstract: OBJECTIVE
  We investigated the incidence of stroke and stroke subtypes in a population-based cohort of patients in France treated with growth hormone (GH) for short stature in childhood.
  
  
  METHODS
  Adult morbidity data were obtained in 2008-2010 for 6,874 children with idiopathic isolated GH deficiency or short stature who started GH treatment between 1985 and 1996. Cerebrovascular events were validated using medical reports and imaging data and classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. Case ascertainment completeness was estimated with capture-recapture methods. The incidence of stroke and of stroke subtypes was calculated and compared with population values extracted from registries in Dijon and Oxford, between 2000 and 2012.
  
  
  RESULTS
  Using both Dijon and Oxford population-based registries as references, there was a significantly higher risk of stroke among patients treated with GH in childhood. The excess risk of stroke was mainly attributable to a very substantially and significantly higher risk of hemorrhagic stroke (standardized incidence ratio from 3.5 to 7.0 according to the registry rates considered, and accounting or not accounting for missed cases), and particularly subarachnoid hemorrhage (standardized incidence ratio from 5.7 to 9.3).
  
  
  CONCLUSIONS
  We report a strong relationship between hemorrhagic stroke and GH treatment in childhood for isolated growth hormone deficiency or childhood short stature. Patients treated with GH worldwide should be advised about this association and further studies should evaluate the potentially causal role of GH treatment in these findings.
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Amélie
authors.initials: A
authors.lastname: Poidvin
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Touzé
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Ecosse
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Landier
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Béjot
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Maurice
authors.initials: M
authors.lastname: Giroud
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Carel
authors.affiliation: From the Biostatistics and Epidemiology Unit (A.P., E.E., J.C.), and APEMAC Equipe d'Accueil 4360, Hôtel Dieu, Assistance Publique-Hôpitaux de Paris, Université de Lorraine and University Paris Descartes, Paris; University Paris Diderot (A.P., F.L., J.-C.C.), Sorbonne Paris Cité; Service d'Endocrinologie Diabétologie Pédiatrique et Centre de Référence des Maladies Endocriniennes Rares de la Croissance (A.P., F.L., J.-C.C.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris; Institut National de la Santé et de la Recherche Médicale Unité CIE-5 (A.P., F.L., J.-C.C.), Paris; Université Caen Basse Normandie (E.T.), Inserm U919, CHU Côte de Nacre, Caen; Dijon Stroke Registry (Y.B., M.G.), EA4184, University Hospital, Medical School of Dijon, University of Burgundy, Dijon, France; and Stroke Prevention Research Unit (P.M.R.), Nuffield Department of Clinical Neuroscience, University of Oxford, UK. joel.coste@htd.aphp.fr.
authors.forename: Joël
authors.initials: J
authors.lastname: Coste
mesh_terms: D000328:Adult; D001827:Body Height / Q000187:drug effects*; D002648:Child; D005602:France / Q000453:epidemiology; D006130:Growth Disorders / Q000188:drug therapy; D019382:Human Growth Hormone / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D019382:Human Growth Hormone