title: Pathophysiology of renal calcium handling in acromegaly: what lies behind hypercalciuria?
abstract: BACKGROUND
  Hypercalciuria is frequent in patients with acromegaly, but it is unclear how GH/IGF-I regulate renal calcium handling. Elevated fasting plasma calcium levels despite increased glomerular filtration suggest enhanced renal calcium reabsorption.
  
  
  OBJECTIVE
  The aim of this study was to investigate the impact of acromegaly on phosphocalcium metabolism.
  
  
  METHODS
  We conducted a prospective sequential study at a tertiary referral medical center and clinical investigation center (www.ClinicalTrials.gov Identifier: NCT00531908).
  
  
  METHODS
  Sixteen consecutive patients (five females/11 males) with acromegaly received a single iv infusion of 25 mg of furosemide to induce an acute increase in calcium and magnesium delivery to distal tubular segments during a high-sodium diet with stable dietary calcium, magnesium, and phosphate intake.
  
  
  METHODS
  Baseline plasma and urine electrolytes, plasma calciotropic hormones, and furosemide-induced changes in the fractional excretion and tubular reabsorption of Na, Ca, and Mg were measured before and 6 months (range, 1-12) after effective treatment of acromegaly.
  
  
  RESULTS
  Serum IGF-I concentrations normalized in all the patients after acromegaly treatment. Compared with controlled acromegaly, active acromegaly was associated with higher fasting plasma (P = 0.0002) and urinary calcium (P = 0.0003) levels, lower PTH levels (P = 0.0075), higher calcitriol levels (P = 0.0137), higher phosphatemia (P<0.0001) and tubular phosphate reabsorption (P = 0.0002), and a lower calciuric (P = 0.0327) but not magnesiuric response to furosemide related to higher baseline and postfurosemide tubular calcium (P = 0.0034 and P = 0.0081, respectively), but not magnesium reabsorption.
  
  
  CONCLUSIONS
  The IGF-I-mediated and PTH-independent increase in calcitriol synthesis in acromegaly is responsible for both absorptive hypercalciuria and increased fasting plasma calcium linked to enhanced distal tubular calcium reabsorption, as shown by the selectively diminished calciuric response to furosemide.
authors.affiliation: Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, 78 rue du Général Leclerc, F-94275 Le Kremlin-Bicêtre, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Kamenický
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Cédric
authors.initials: C
authors.lastname: Gauci
authors.forename: Sylvie
authors.initials: S
authors.lastname: Salenave
authors.forename: Alexia
authors.initials: A
authors.lastname: Letierce
authors.forename: Marc
authors.initials: M
authors.lastname: Lombès
authors.forename: Sylvie
authors.initials: S
authors.lastname: Brailly-Tabard
authors.forename: Michel
authors.initials: M
authors.lastname: Azizi
authors.forename: Dominique
authors.initials: D
authors.lastname: Prié
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Souberbielle
authors.forename: Philippe
authors.initials: P
authors.lastname: Chanson
mesh_terms: D000172:Acromegaly / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D000328:Adult; D000368:Aged; D002117:Calcitriol / Q000096:biosynthesis / Q000097:blood; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000097:blood*; D004232:Diuretics / Q000008:administration & dosage; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005665:Furosemide / Q000008:administration & dosage*; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D053565:Hypercalciuria / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000008:administration & dosage / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood
chemical_list: D002136:Calcium, Dietary; D004232:Diuretics; D010281:Parathyroid Hormone; D010710:Phosphates; D012709:Serum Albumin; D017673:Sodium Chloride, Dietary; D019382:Human Growth Hormone; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D005665:Furosemide; D000089703:Fibroblast Growth Factor-23; C104450:25-hydroxyvitamin D; D002117:Calcitriol; D008274:Magnesium