title: Body fluid expansion in acromegaly is related to enhanced epithelial sodium channel (ENaC) activity.
abstract: BACKGROUND
  Soft-tissue swelling and increased extracellular volume, two features of acromegaly, are related to the antinatriuretic effects of excess GH/IGF-I, but the precise pathophysiological mechanism is unclear.
  
  
  OBJECTIVE
  Our objective was to determine the effect of the GH excess on renal and extrarenal epithelial sodium channel (ENaC) activity.
  
  
  METHODS
  We conducted a prospective randomized open-label blinded-endpoint (PROBE) crossover study (www.ClinicalTrials.gov Identifier: NCT00531908) at a tertiary referral medical center and clinical investigation center.
  
  
  METHODS
  Sixteen patients (five females, 11 males) with acromegaly were randomly assigned to receive 20 mg amiloride (an ENaC blocker) and 25 mg furosemide (a Na-K-2Cl cotransporter blocker) under a high-sodium diet to suppress endogenous renin and aldosterone.
  
  
  METHODS
  Diuretic-induced changes in the urinary Na/K ratio (reflecting coupling between ENaC-mediated Na reabsorption and distal K secretion) and the intranasal amiloride-sensitive potential (reflecting extrarenal ENaC activity) were measured before and 6 months after (range, 1-12 months) treatment of acromegaly.
  
  
  RESULTS
  Serum IGF-I concentrations normalized in all the patients after treatment of acromegaly. Baseline plasma renin and aldosterone concentrations remained unchanged after treatment. Active acromegaly, compared with controlled disease, was associated with an enhanced response [median (interquartile range)] to amiloride [urinary Na/K, 13.9 (9.8-19.5) vs. 6.3 (4.3-8.4) mmol/mmol, P = 0.0003], a reduced response to furosemide [urinary Na/K, 5.2 (4.6-7.2) vs. 7.1 (5.4-8.8) mmol/mmol, P =0.0151], and an increased intranasal amiloride-sensitive potential [5.8 (11.9-3.8) vs. 4.2 (6.4-2.1) mV, P = 0.031], respectively.
  
  
  CONCLUSIONS
  GH/IGF-I excess in humans is associated with enhanced renal and extrarenal ENaC activity that may contribute to soft-tissue swelling and volume expansion in acromegaly.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Le Kremlin Bicêtre F-94275, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Kamenicky
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Michael
authors.initials: M
authors.lastname: Frank
authors.forename: Sylvie
authors.initials: S
authors.lastname: Salenave
authors.forename: Alexia
authors.initials: A
authors.lastname: Letierce
authors.forename: Michel
authors.initials: M
authors.lastname: Azizi
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
mesh_terms: D000172:Acromegaly / Q000150:complications* / Q000378:metabolism; D000450:Aldosterone / Q000097:blood; D000584:Amiloride / Q000494:pharmacology / Q000627:therapeutic use*; D001826:Body Fluids / Q000187:drug effects*; D018592:Cross-Over Studies; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D005260:Female; D005665:Furosemide / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D012083:Renin / Q000097:blood; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004232:Diuretics; D053503:Epithelial Sodium Channels; D049994:Sodium Potassium Chloride Symporter Inhibitors; D000450:Aldosterone; D007334:Insulin-Like Growth Factor I; D000584:Amiloride; D005665:Furosemide; D012083:Renin