title: Growth hormone/IGF-1 axis longitudinal evaluation in clinically isolated syndrome patients on interferon β-1b therapy: stimulation tests and correlations with clinical and radiological conversion to multiple sclerosis.
abstract: Growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis abnormalities in multiple sclerosis (MS) suggest their role in its pathogenesis. Interferon β (IFN-β) efficacy could be mediated also by an increase of IGF-1 levels. A 2-year longitudinal study was performed to estimate the prevalence of GH and/or IGF-1 deficiency in clinically isolated syndrome (CIS) patients and their correlation with conversion to MS in IFN treated patients.
  
  
  
  Clinical and demographic features of CIS patients were collected before the start of IFN-β-1b. IGF-1 levels and GH response after arginine and GH releasing hormone + arginine stimulation tests were assessed. Clinical and magnetic resonance imaging evaluations were performed at baseline, 1 year and 2 years.
  
  
  
  Thirty CIS patients (24 female) were enrolled. At baseline, four patients (13%) showed a hypothalamic GH deficiency (GHD), whilst no one had a pituitary GHD. Baseline demographic, clinical and radiological data were not related to GHD, whilst IGF-1 levels were inversely related to age (P < 0.001) and GH levels (P = 0.03). GH and IGF-1 serum mean levels were not significantly modified after 1 and 2 years of treatment in the whole group, although 3/4 GHD patients experienced a normalization of GH levels, whilst one dropped out. After 2 years of treatment 13/28 (46%) patients converted to MS. The presence of GHD and GH and IGF-1 levels were not predictive of relapses, new T2 lesions or conversion occurrence.
  
  
  
  Growth hormone/IGF-1 axis function was found to be frequently altered in CIS patients, but this was not related to MS conversion. Patients experienced an improvement of GHD during IFN therapy. Longer follow-up is necessary to assess its impact on disease progression.
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: R
authors.identifier: 0000-0001-6388-8180
authors.initials: R
authors.lastname: Lanzillo
authors.affiliation: IRCSS SDN, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Di Somma
authors.affiliation: Biostructure and Bioimaging Institute (IBB), National Research Council (CNR), Naples, Italy.
authors.forename: M
authors.identifier: 0000-0001-7836-454X
authors.initials: M
authors.lastname: Quarantelli
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carotenuto
authors.affiliation: IRCSS SDN, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pivonello
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: M
authors.identifier: 0000-0003-2613-3090
authors.initials: M
authors.lastname: Moccia
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cianflone
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Marsili
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Puorro
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Saccà
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: C V
authors.initials: CV
authors.lastname: Russo
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: C
authors.initials: C
authors.lastname: De Luca Picione
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Ausiello
authors.affiliation: IRCSS SDN, Naples, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.affiliation: Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Brescia Morra
mesh_terms: D000328:Adult; D001120:Arginine / Q000494:pharmacology; D018450:Disease Progression; D004568:Electrodiagnosis; D005260:Female; D005500:Follow-Up Studies; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D000068576:Interferon beta-1b / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D009460:Neurologic Examination; D016896:Treatment Outcome
chemical_list: C583557:IGF1 protein, human; D019382:Human Growth Hormone; D000068576:Interferon beta-1b; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine
keywords: clinically isolated syndrome; conversion; growth hormone; insulin-like growth factor; interferon beta-1b; multiple sclerosis; stimulation test