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

Pituitary. 2016 Jun;19(3):332-41. doi: 10.1007/s11102-016-0712-7.


Context: 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.

Design: 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.

Conclusion: 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.

Keywords: Adrenal insufficiency; Adult growth hormone deficiency; Diagnosis; Glucagon stimulation test; Weight based.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adenoma / complications
  • Adrenal Insufficiency / diagnosis*
  • Adrenal Insufficiency / etiology
  • Adrenal Insufficiency / metabolism
  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Body Weight
  • Case-Control Studies
  • Central Nervous System Cysts / complications
  • Cosyntropin
  • Craniopharyngioma / complications
  • Dose-Response Relationship, Drug
  • Female
  • Glucagon*
  • Hormones*
  • Human Growth Hormone / metabolism*
  • Humans
  • Hydrocortisone / metabolism*
  • Hypoglycemic Agents
  • Hypopituitarism / diagnosis*
  • Hypopituitarism / etiology
  • Hypopituitarism / metabolism
  • Hypothalamo-Hypophyseal System / metabolism*
  • Insulin
  • Male
  • Middle Aged
  • Pituitary Neoplasms / complications
  • Pituitary-Adrenal System / metabolism*
  • Reference Values
  • Sensitivity and Specificity


  • Blood Glucose
  • Hormones
  • Hypoglycemic Agents
  • Insulin
  • Human Growth Hormone
  • Cosyntropin
  • Glucagon
  • Hydrocortisone