title: Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency.
abstract: BACKGROUND
  In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.
  
  
  OBJECTIVE
  The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.
  
  
  METHODS
  This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29)NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.
  
  
  METHODS
  Peak GH area under the receiver operating characteristic curve after macimorelin was measured.
  
  
  RESULTS
  Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 ± 5.69 and 17.71 ± 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with 82% sensitivity, 92% specificity, and 13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.
  
  
  CONCLUSIONS
  Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, 2002 Holcombe Boulevard, Building 109, Room 210, Houston, Texas 77030, USA. jgarcia1@bcm.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Garcia
authors.forename: R
authors.initials: R
authors.lastname: Swerdloff
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Kyle
authors.forename: M
authors.initials: M
authors.lastname: Kipnes
authors.forename: B M K
authors.initials: BM
authors.lastname: Biller
authors.forename: D
authors.initials: D
authors.lastname: Cook
authors.forename: K C J
authors.initials: KC
authors.lastname: Yuen
authors.forename: V
authors.initials: V
authors.lastname: Bonert
authors.forename: A
authors.initials: A
authors.lastname: Dobs
authors.forename: M E
authors.initials: ME
authors.lastname: Molitch
authors.forename: G R
authors.initials: GR
authors.lastname: Merriam
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001120:Arginine; D018592:Cross-Over Studies; D005260:Female; D054439:Ghrelin / Q000031:analogs & derivatives*; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency*; D006801:Humans; D007211:Indoles; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D014364:Tryptophan / Q000031:analogs & derivatives*
chemical_list: D054439:Ghrelin; D007211:Indoles; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C582727:macimorelin; D014364:Tryptophan; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine
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