title: Overweight/Obese adults with pituitary disorders require lower peak growth hormone cutoff values on glucagon stimulation testing to avoid overdiagnosis of growth hormone deficiency.
abstract: BACKGROUND
  Obesity is associated with diminished GH secretion, which may result in the overdiagnosis of adult GH deficiency (GHD) in overweight/obese pituitary patients. However, there are no body mass index (BMI)-specific peak GH cutoffs for the glucagon stimulation test (GST), the favored dynamic test for assessing adult GHD in the United States.
  
  
  OBJECTIVE
  The objective of the study was to determine a peak GH cutoff level for the diagnosis of adult GHD in overweight/obese individuals using the GST.
  
  
  METHODS
  This was a retrospective, cross-sectional study.
  
  
  METHODS
  The study was conducted at Massachusetts General Hospital and Oregon Health and Science University.
  
  
  METHODS
  A total of 108 subjects with a BMI ≥ 25 kg/m(2) were studied: healthy controls (n = 47), subjects with total pituitary deficiency (TPD) (n = 20, ≥ 3 non-GH pituitary hormone deficiencies), and subjects with partial pituitary deficiency (PPD) (n = 41, 1-2 non-GH pituitary hormone deficiencies).
  
  
  METHODS
  The intervention consisted of a standard 4-hour GST.
  
  
  METHODS
  The main outcome measure was peak GH level on GST.
  
  
  RESULTS
  Using the standard peak GH cutoff of 3 ng/mL, 95% of TPD cases (19 of 20), 80% of PPD (33 of 41), and 45% of controls (21 of 47) were classified as GHD. In receiver-operator characteristic curve analysis (controls vs TPD), a peak GH value of 0.94 ng/mL provided the greatest sensitivity (90%) and specificity (94%). Using a peak GH cutoff of 1 ng/mL, 6% of controls (3 of 47), 59% of PPDs (24 of 41), and 90% of TPDs (18 of 20) were classified as GHD. BMI (R = -0.35, P = .02) and visceral adipose tissue (R = -0.32, P = .03) negatively correlated with peak GH levels in controls.
  
  
  CONCLUSIONS
  A large proportion of healthy overweight/obese individuals (45%) failed the GST using the standard 3 ng/mL GH cutoff. Overweight/obese pituitary patients are at risk of being misclassified as GHD using this cutoff level. A 1-ng/mL GH cutoff may reduce the overdiagnosis of adult GHD in overweight/obese patients.
authors.affiliation: Neuroendocrine Unit (L.E.D., B.M.K.B., K.K.M.) and Department of Radiology (M.A.B.), Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114; Neuroendocrine Unit (A.V.G., B.M.R., A.D.R., M.H.G.) and Clinical Pathology Core Laboratory (P.M.S.), Massachusetts General Hospital, Boston, Massachusetts 02114; and Division of Endocrinology, Diabetes, and Clinical Nutrition (K.C.J.Y.), Department of Medicine, Oregon Health and Science University, Portland, Oregon 97239.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Dichtel
authors.forename: Kevin C J
authors.initials: KC
authors.lastname: Yuen
authors.forename: Miriam A
authors.initials: MA
authors.lastname: Bredella
authors.forename: Anu V
authors.initials: AV
authors.lastname: Gerweck
authors.forename: Brian M
authors.initials: BM
authors.lastname: Russell
authors.forename: Ariana D
authors.initials: AD
authors.lastname: Riccio
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Gurel
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Sluss
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
authors.forename: Karen K
authors.initials: KK
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D001823:Body Composition / Q000187:drug effects; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005934:Glucagon / Q000009:adverse effects; D019382:Human Growth Hormone / Q000097:blood* / Q000172:deficiency*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D050177:Overweight / Q000097:blood*; D010900:Pituitary Diseases / Q000097:blood*; D012016:Reference Values; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone; D005934:Glucagon