title: Adrenal steroidogenesis after B lymphocyte depletion therapy in new-onset Addison's disease.
abstract: BACKGROUND
  A diagnosis of Addison's disease means lifelong dependence on daily glucocorticoid and mineralocorticoid therapy and is associated with increased morbidity and mortality as well as a risk of unexpected adrenal crisis.
  
  
  OBJECTIVE
  The objective of the study was to determine whether immunomodulatory therapy at an early stage of autoimmune Addison's disease could lead to preservation or improvement in adrenal steroidogenesis.
  
  
  METHODS
  This was an open-label, pilot study of B lymphocyte depletion therapy in new-onset idiopathic primary adrenal failure. Doses of iv rituximab (1 g) were given on d 1 and 15, after pretreatment with 125 mg iv methylprednisolone.
  
  
  METHODS
  Six patients (aged 17-47 yr; four females) were treated within 4 wk of the first diagnosis of idiopathic primary adrenal failure. Dynamic testing of adrenal function was performed every 3 months for at least 12 months.
  
  
  RESULTS
  Serum cortisol levels declined rapidly and were less than 100 nmol/liter (3.6 μg/dl) in all patients by 3 months after B lymphocyte depletion. Serum cortisol and aldosterone concentrations remained low in five of the six patients throughout the follow-up period. However, a single patient had sustained improvement in both serum cortisol [peak 434 nmol/liter (15.7 μg/dl)] and aldosterone [peak 434 pmol/liter (15.7 ng/dl)] secretion. This patient was able to discontinue steroid medications 15 months after therapy and remains well, with improving serum cortisol levels 27 months after therapy.
  
  
  CONCLUSIONS
  New-onset autoimmune Addison's disease should be considered as a potentially reversible condition in some patients. Future studies of immunomodulation in autoimmune Addison's disease may be warranted.
authors: Newcastle University, Newccastle upon Tyne Hospitals National Health Service Foundation Trust, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom. s.h.s.pearce@ncl.ac.uk
authors: Simon H S
authors: SH
authors: Pearce
authors: Anna L
authors: AL
authors: Mitchell
authors: Stuart
authors: S
authors: Bennett
authors: Phil
authors: P
authors: King
authors: Sukesh
authors: S
authors: Chandran
authors: Sath
authors: S
authors: Nag
authors: Shu
authors: S
authors: Chen
authors: Bernard Rees
authors: BR
authors: Smith
authors: John D
authors: JD
authors: Isaacs
authors: Bijay
authors: B
authors: Vaidya
mesh_terms: D000224:Addison Disease / Q000188:drug therapy* / Q000276:immunology*; D000293:Adolescent; D000302:Adrenal Cortex / Q000276:immunology; D000328:Adult; D000450:Aldosterone / Q000097:blood*; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007155:Immunologic Factors / Q000008:administration & dosage; D008212:Lymphocyte Depletion / Q000379:methods*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D005938:Glucocorticoids; D007155:Immunologic Factors; D000450:Aldosterone; D000069283:Rituximab; D006854:Hydrocortisone; D008775:Methylprednisolone