title: Evidence for persistent dysfunction of wild-type aldosterone synthase gene in glucocorticoid-treated familial hyperaldosteronism type I.
abstract: BACKGROUND
  In familial hyperaldosteronism type I (FH-I), glucocorticoid treatment suppresses adrenocorticotrophic hormone-regulated hybrid gene expression and corrects hyperaldosteronism.
  
  
  OBJECTIVE
  To determine whether the wild-type aldosterone synthase genes, thereby released from chronic suppression, are capable of functioning normally.
  
  
  METHODS
  We compared mid-morning levels of plasma potassium, plasma aldosterone, plasma renin activity (PRA) and aldosterone: PRA ratios, measured with patients in an upright position, and responsiveness of aldosterone levels to infusion of angiotensin II (AII), for 11 patients with FH-I before and during long-term (0.8-14.3 years) treatment with 0.25-0.75 mg/day dexamethasone or 2.5-10 mg/day prednisolone.
  
  
  RESULTS
  During glucocorticoid treatment, hypertension was corrected in all. Potassium levels, which had been low (< 3.5 mmol/l) in two patients before treatment, were normal in all during treatment (mean 4.0+/-0.1 mmol/l, range 3.5-4.6). Aldosterone levels during treatment [13.2+/-2.1 ng/100 ml (mean+/-SEM)] were lower than those before treatment (20.1+/-2.5 ng/100 ml, P< 0.05). PRA levels, which had been suppressed before treatment (0.5+/-0.2 ng/ml per h), were unsuppressed during treatment (5.1+/-1.5 ng/ml per h, P< 0.01) and elevated (> 4 ng/ml per h) in six patients. Aldosterone: PRA ratios, which had been elevated (> 30) before treatment (101.1+/-25.9), were much lower during treatment (4.1+/-1.0, P< 0.005) and below normal (< 5) in eight patients. Surprisingly, aldosterone level, which had not been responsive (< 50% rise) to infusion of AII for all 11 patients before treatment, remained unresponsive for 10 during treatment.
  
  
  CONCLUSIONS
  Apparently regardless of duration of glucocorticoid treatment in FH-I, aldosterone level remains poorly responsive to AII, with a higher than normal PRA and a low aldosterone: PRA ratio. This is consistent with there being a persistent defect in functioning of wild-type aldosterone synthase gene.
authors.affiliation: University Department of Medicine, Greenslopes Hospital, Brisbane, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Stowasser
authors.forename: W L
authors.initials: WL
authors.lastname: Taylor
authors.forename: M G
authors.initials: MG
authors.lastname: Gartside
authors.forename: T J
authors.initials: TJ
authors.lastname: Tunny
authors.forename: R D
authors.initials: RD
authors.lastname: Gordon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000008:administration & dosage; D015139:Blotting, Southern; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D006973:Hypertension / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000097:blood; D011239:Prednisolone / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D014662:Vasoconstrictor Agents / Q000008:administration & dosage
chemical_list: D005938:Glucocorticoids; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D000450:Aldosterone; D003907:Dexamethasone; D011239:Prednisolone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin; D011188:Potassium