title: Enhanced Na+/H+ exchange in Cushing's syndrome reflects functional hypermineralocorticoidism.
abstract: BACKGROUND
  Patients with Cushing's syndrome exhibit a bimodal distribution of maximal rates of the erythrocyte amiloride-sensitive Na+/H+ exchange (NHE). Enhanced erythrocyte NHE has recently been found in patients with primary aldosteronism.
  
  
  OBJECTIVE
  To test the hypothesis that occult hypermineralocorticoidism in a subset of patients with Cushing's syndrome is responsible for the greater than normal NHE.
  
  
  METHODS
  NHE was measured as maximal initial rate (Vmax) of amiloride-inhibited efflux of H+ into an alkaline Na+-containing medium, for 47 patients with hypercortisolism (20 with pituitary adenomas, 18 with adrenal adenomas, and nine with ectopic production of adrenocorticotropin). Clinical appearance, blood pressure levels, plasma aldosterone and deoxycorticosterone levels, serum electrolytes, and urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios were assessed for all patients. Twenty patients (10 with greater than normal NHE and 10 with low-to-normal NHE) were randomly selected from 47 patients with hypercortisolism, and treated with 200 mg/day spironolactone for 7 days. NHE in these patients was assessed before starting the treatment and 2 days after its cessation.
  
  
  RESULTS
  Greater than normal NHE (Vmax) was associated with peripheral edema, high diastolic blood pressure, hypokalemia, and high urine (tetrahydrocortisol plus 5-alpha-tetrahydrocortisol) : tetrahydrocortisone ratios. The enhanced NHE was rapidly normalized by treatment with spironolactone.
  
  
  CONCLUSIONS
  Erythrocyte NHE in patients with hypercortisolism and functional hypermineralocorticoidism is greater than normal due to incomplete peripheral conversion of cortisol (which binds to mineralocorticoid receptors) into metabolically inactive cortisone.
authors.affiliation: Chorley Institute for Hypertension, Chaim Sheba Medical Center Tel Hashomer, Israel. korenw@netvision.net.il
authors.forename: W
authors.initials: W
authors.lastname: Koren
authors.forename: A
authors.initials: A
authors.lastname: Grienspuhn
authors.forename: S R
authors.initials: SR
authors.lastname: Kuznetsov
authors.forename: M
authors.initials: M
authors.lastname: Berezin
authors.forename: T
authors.initials: T
authors.lastname: Rosenthal
authors.forename: Y V
authors.initials: YV
authors.lastname: Postnov
mesh_terms: D000328:Adult; D003348:Cortisone / Q000378:metabolism; D003480:Cushing Syndrome / Q000097:blood* / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D017136:Ion Transport; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008901:Mineralocorticoids / Q000097:blood* / Q000652:urine; D017923:Sodium-Hydrogen Exchangers / Q000097:blood*
chemical_list: D008901:Mineralocorticoids; D017923:Sodium-Hydrogen Exchangers; D003348:Cortisone; D006854:Hydrocortisone