Overweight/Obese Adults With Pituitary Disorders Require Lower Peak Growth Hormone Cutoff Values on Glucagon Stimulation Testing to Avoid Overdiagnosis of Growth Hormone Deficiency

Context: 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. Design: This was a retrospective, cross-sectional study. Setting: 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/m2 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). Intervention: The intervention consisted of a standard 4-hour GST. Main Outcome Measures: 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. Conclusion: 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.