title: The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.
abstract: OBJECTIVE
  Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated.
  
  
  METHODS
  Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy.
  
  
  RESULTS
  H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone.
  
  
  CONCLUSIONS
  Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.
authors.affiliation: Division of Oncological Endocrinology, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Via Genova 3, 10126, Turin, Italy. rita.berardelli@unito.it.
authors.forename: R
authors.initials: R
authors.lastname: Berardelli
authors.affiliation: Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Karamouzis
authors.affiliation: Division of Oncological Endocrinology, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Via Genova 3, 10126, Turin, Italy.
authors.forename: V
authors.initials: V
authors.lastname: D'Angelo
authors.affiliation: Division of Oncological Endocrinology, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Via Genova 3, 10126, Turin, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Fussotto
authors.affiliation: Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Minetto
authors.affiliation: Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Turin, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Giordano
authors.affiliation: Division of Oncological Endocrinology, Department of Medical Sciences, Azienda Ospedaliera Città della Salute e della Scienza, Via Genova 3, 10126, Turin, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Arvat
mesh_terms: D000208:Acute Disease; D000224:Addison Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D005260:Female; D005438:Fludrocortisone / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D018161:Receptors, Mineralocorticoid / Q000819:agonists*
chemical_list: D000893:Anti-Inflammatory Agents; D018161:Receptors, Mineralocorticoid; D005438:Fludrocortisone; D006854:Hydrocortisone
keywords: Adrenal cortex; Fludrocortisone; GR; HPA axis; MR