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

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/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).

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.

Trial registration: ClinicalTrials.gov NCT00131378.

Figures

Figure 1.

A, Percentage of subjects with failed GST using a peak GH cutoff of 3 ng/mL (■) vs percentage with failed GST using a peak GH cutoff of 1 ng/mL (□). B, Percentage of subjects per group diagnosed with GHD using the standard cutoff of 3 ng/mL that would be reclassified as GH sufficient using the cutoff of 1 ng/mL for glucagon stimulation testing.

Figure 2.

A, ROC curve of peak GH level on GST to detect GHD. The AUC is 0.93 (P < .0001). *, Designates point of optimized sensitivity (94%) and specificity (90%) on ROC curve corresponding to a cutoff of at 0.94 ng/mL for diagnosis of GHD. B, ROC curve assessment at GH cutoff of 0.94 ng/mL for diagnosis of GHD (designated by an asterisk). Solid line represents sensitivity and dotted line represents specificity.

Figure 3.

Timing of peak in controls (black), patients with PPD (gray), and TPD (white) represented as a percentage of each group. Of note, no control subject had an absent GH peak.