title: Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic-pituitary-adrenal axes in adults: results from a prospective randomized multicenter study.
abstract: BACKGROUND
  Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic-pituitary-adrenal (HPA) axes using weight-based dosing for the GST.
  
  
  OBJECTIVE
  To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively.
  
  
  METHODS
  28 Patients with hypothalamic-pituitary disease and 1-2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order.
  
  
  RESULTS
  Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = -0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST.
  
  
  CONCLUSIONS
  The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, Cleveland, OH, 44022, USA. hamraha@clevelandclinicabudhabi.ae.|Department of Endocrinology, Medical Subspecialty Institute, Cleveland Clinic Abu Dhabi, 7th Floor, Swing Wing, Al Maryah Island, PO Box 112412, Abu Dhabi, UAE. hamraha@clevelandclinicabudhabi.ae.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Hamrahian
authors.affiliation: Swedish Pituitary Center, Swedish Neuroscience Institute, Seattle, WA, 98122, USA.
authors.forename: Kevin C J
authors.initials: KC
authors.lastname: Yuen
authors.affiliation: Department of Medicine and Neurosurgery, Allegheny Neuroendocrinology Center, Allegheny General Hospital, Pittsburgh, PA, 15212, USA.
authors.forename: Murray B
authors.initials: MB
authors.lastname: Gordon
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Pulaski-Liebert
authors.affiliation: Quantitatve Health Sciences, Lerner Research Institute, Cleveland, OH, 44195, USA.
authors.forename: James
authors.initials: J
authors.lastname: Bena
authors.affiliation: Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
authors.forename: Beverly M K
authors.initials: BM
authors.lastname: Biller
mesh_terms: D000236:Adenoma / Q000150:complications; D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D016022:Case-Control Studies; D020863:Central Nervous System Cysts / Q000150:complications; D003366:Cosyntropin; D003397:Craniopharyngioma / Q000150:complications; D004305:Dose-Response Relationship, Drug; D005260:Female; D005934:Glucagon; D006728:Hormones; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007004:Hypoglycemic Agents; D007018:Hypopituitarism / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007328:Insulin; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000150:complications; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D001786:Blood Glucose; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin; D019382:Human Growth Hormone; D003366:Cosyntropin; D005934:Glucagon; D006854:Hydrocortisone
keywords: Adrenal insufficiency; Adult growth hormone deficiency; Diagnosis; Glucagon stimulation test; Weight based