title: Strategies for managing ACTH dependent mineralocorticoid excess induced by abiraterone.
abstract: BACKGROUND
  Abiraterone strongly inhibits androgen synthesis but may lead to an increase in mineralocorticoid hormones that may impair its long term tolerability in patients with prostate cancer. How to implement available therapies in the management and prevention of these potential side effects is a matter of current clinical research.
  
  
  METHODS
  The acute and long term consequences of mineralocorticoid excess and the effects of available treatments have been reviewed. Prospective studies in which abiraterone was employed were identified to assess the frequency and severity of the mineralocorticoid excess syndrome and the efficacy of ameliorating therapeutic approaches.
  
  
  RESULTS
  Glucocorticoids to inhibit the ACTH increase that drives mineralocorticoid synthesis and mineralocorticoid receptor (MR) antagonists can be used in the management of the abiraterone-induced mineralocorticoid excess syndrome. Phase I and II trials of abiraterone without additional therapies revealed that mineralocorticoid excess symptoms occur in the majority of patients. Eplerenone, a specific MR antagonist, seems to be effective but it does not control the mineralocorticoid excess. Glucorticoid supplementation to control ACTH drive is therefore needed. In several randomized trials the addition of prednisone (10mg daily) to abiraterone was not able to prevent mineralocorticoid excess syndrome in many cases and thus cannot be considered the gold standard.
  
  
  CONCLUSIONS
  At present, the best conceivable treatment for managing the abiraterone-induced mineralocorticoid excess consists of the administration of glucocorticoid replacement at the lowest effective dose ± MR antagonists and salt deprivation. The drug doses should be modulated by monitoring blood pressure, fluid retention and potassium levels during therapy.
authors.affiliation: Endocrinology Unit, Azienda Ospedaliero Universitaria San Luigi, Orbassano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pia
authors.forename: Francesca
authors.initials: F
authors.lastname: Vignani
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Bironzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scagliotti
authors.forename: Wiebke
authors.initials: W
authors.lastname: Arlt
authors.forename: Massimo
authors.initials: M
authors.lastname: Terzolo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000009:adverse effects* / Q000627:therapeutic use; D000736:Androstenes; D000737:Androstenols / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D043204:Mineralocorticoid Excess Syndrome, Apparent / Q000139:chemically induced* / Q000378:metabolism; D008901:Mineralocorticoids / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000736:Androstenes; D000737:Androstenols; D008901:Mineralocorticoids; D000324:Adrenocorticotropic Hormone; C089740:abiraterone
keywords: ACTH; Abiraterone acetato; Mineralcorticoid excess; Prostate cancer; Steroid supplementation