title: Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.
abstract: BACKGROUND
  Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility.
  
  
  OBJECTIVE
  We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease.
  
  
  METHODS
  Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility.
  
  
  METHODS
  The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy.
  
  
  METHODS
  Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study.
  
  
  RESULTS
  Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement.
  
  
  CONCLUSIONS
  This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.
authors.affiliation: Institute of Genetic Medicine (E.H.G., K.M., A.L.M., P.P., R.Q., S.H.S.P.), Newcastle University, Newcastle upon Tyne NE1 3BZ, United Kingdom; the Endocrine Unit (E.H.G., A.L.M., P.P., S.G.B., R.A.J., R.Q., S.H.S.P.), Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, United Kingdom; the Centre for Endocrinology, Diabetes, and Metabolism (B.A.H., W.A.), University of Birmingham, Birmingham B15 2TT, United Kingdom; and RSR Ltd (S.C., J.F.), FIRS Laboratories, Cardiff CF4 5DU, United Kingdom.
authors.forename: Earn H
authors.initials: EH
authors.lastname: Gan
authors.forename: Katie
authors.initials: K
authors.lastname: MacArthur
authors.forename: Anna L
authors.initials: AL
authors.lastname: Mitchell
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Hughes
authors.forename: Petros
authors.initials: P
authors.lastname: Perros
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.forename: R Andrew
authors.initials: RA
authors.lastname: James
authors.forename: Richard
authors.initials: R
authors.lastname: Quinton
authors.forename: Shu
authors.initials: S
authors.lastname: Chen
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Furmaniak
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Simon H S
authors.initials: SH
authors.lastname: Pearce
mesh_terms: D000224:Addison Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000097:blood / Q000652:urine; D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology*; D000328:Adult; D000368:Aged; D003366:Cosyntropin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D003366:Cosyntropin; C006418:adrenocorticotropin zinc