title: Mineralocorticoid excess and inhibition of 11 beta-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome.
abstract: OBJECTIVE
  11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. We hypothesize that 11 beta-dehydrogenase is inhibited by ACTH, providing a mechanism whereby cortisol induces hypokalaemic alkalosis in ectopic ACTH syndrome.
  
  
  METHODS
  The principal sources of plasma cortisone were assessed by selective venous catheterization with measurement of cortisol and cortisone by radioimmunoassays. The effect of ACTH on peripheral plasma cortisol/cortisone ratio was assessed in healthy volunteers during circadian rhythm, insulin induced hypoglycaemia, and infusions with exogenous ACTH or cortisol. In patients with Cushing's syndrome plasma cortisol/cortisone ratios were related to plasma potassium, corticosterone, and 11-deoxycorticosterone concentrations.
  
  
  METHODS
  Catheterization was performed in 24 patients with valvular or ischaemic heart disease. Cushing's syndrome patients included: 15 with pituitary adenoma; two with adrenal adenoma; and nine with ectopic ACTH secretion.
  
  
  RESULTS
  Plasma cortisol/cortisone ratios were low in renal vein and high in hepatic vein. In healthy volunteers plasma cortisone increased during cortisol infusion but did not change with increases in endogenous or exogenous ACTH. Plasma cortisol/cortisone ratios were higher in ectopic ACTH syndrome than in other forms of Cushing's syndrome. However, the cortisol/cortisone ratio was no better a predictor of hypokalaemia than the levels of 11-deoxycorticosterone or corticosterone.
  
  
  CONCLUSIONS
  Peripheral conversion of cortisol to cortisone occurs mainly in the kidney and is inhibited by ACTH. In ectopic ACTH syndrome the characteristic mineralocorticoid excess can be accounted for by a combination of increased secretion of cortisol, corticosterone and of 11-deoxycorticosterone and decreased inactivation of cortisol and corticosterone by 11 beta-dehydrogenase.
authors.affiliation: University of Edinburgh, Department of Medicine, Western General Hospital, Scotland, UK.
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: J C
authors.initials: JC
authors.lastname: Campbell
authors.forename: R
authors.initials: R
authors.lastname: Fraser
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
authors.forename: C R
authors.initials: CR
authors.lastname: Edwards
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000182:ACTH Syndrome, Ectopic / Q000097:blood*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D000328:Adult; D000368:Aged; D003345:Corticosterone / Q000378:metabolism; D003348:Cortisone / Q000097:blood*; D003480:Cushing Syndrome / Q000097:blood*; D003900:Desoxycorticosterone / Q000378:metabolism; D006503:Hepatic Veins; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D012082:Renal Veins
chemical_list: D003900:Desoxycorticosterone; D000324:Adrenocorticotropic Hormone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone; D003345:Corticosterone; D006854:Hydrocortisone