title: Long-term outcome of Graves' orbitopathy following high-dose intravenous glucocorticoids and orbital radiotherapy.
abstract: OBJECTIVE
  Intravenous (iv) glucocorticoids (GC) (ivGC) and orbital radiotherapy (ORT) are commonly used in active Graves' orbitopathy (GO), with favorable outcomes in up to 80% of patients. However, little is known on the factors that may affect GO outcome in the long term, an issue that we investigated here.
  
  
  METHODS
  We studied retrospectively 96 untreated patients with GO, identified out of 787 consecutive patients who came to our GO Clinic for a follow-up visit between September 2010 and June 2013. After the first observation, patients were treated with ivGC and ORT and were then re-examined after a median period of 55.5 months. The primary end-point was the possible relation between GO outcome and several individual variables.
  
  
  RESULTS
  Exophthalmometry, eyelid aperture, CAS, diplopia and visual acuity (the latter only in patients with an initial reduction) improved significantly after treatment. Overall, 67.7% of patients had improved and were considered as responders, whereas the remaining (29.1% stable and 4.5% worsened) were considered as non-responders. Age, smoking, thyroid volume, thyroid treatment, serum anti-TSH receptor autoantibodies and individual GO features at first observation did not affect the outcome of GO, which, in contrast, was affected by gender and by the time elapsed between first and last observation. Thus, the prevalence of responders was higher in females (76.4 vs 48% in males, P = 0.02) and the time elapsed between first and last observation was greater in responders (58 vs 39 months in non-responders, P = 0.02). Whereas the prevalence of responders and non-responders was similar up to 36 months, there was an increase in responders beginning between 37 and 48 months and reaching a peak of ~80% between 61 and 72 months, to plateau thereafter.
  
  
  CONCLUSIONS
  Given the limitations of retrospective investigations, our study confirms that the combination of GC and ORT is effective in GO and shows that females have greater chances to respond to treatment. The notorious tendency of GO to improve spontaneously with time most likely contributes the long-term outcome of the eye syndrome.
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Sisti
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Menconi
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Leo
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Profilo
authors.affiliation: Ophthalmopathy Unit I, Department of Surgical, Medical and Molecular Pathology, University of Pisa and University Hospital of Pisa, Pisa, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Mautone
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Mazzi
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Rocchi
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Latrofa
authors.affiliation: Ophthalmopathy Unit I, Department of Surgical, Medical and Molecular Pathology, University of Pisa and University Hospital of Pisa, Pisa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Nardi
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Vitti
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Marcocci
authors.affiliation: Endocrinology Units, Department of Clinical and Experimental Medicine, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy. michele.marino@med.unipi.it.
authors.forename: M
authors.initials: M
authors.lastname: Marinò
mesh_terms: D000328:Adult; D000368:Aged; D003131:Combined Modality Therapy; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D049970:Graves Ophthalmopathy / Q000188:drug therapy / Q000503:physiopathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D013961:Thyroid Gland / Q000503:physiopathology*; D016896:Treatment Outcome; D014792:Visual Acuity / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D008775:Methylprednisolone
keywords: Age; Glucocorticoids; Graves’ disease; Graves’ orbitopathy; Natural history; Radiotherapy