Body Mass Index Determines Evoked Growth Hormone (GH) Responsiveness in Normal Healthy Male Subjects: Diagnostic Caveat for Adult GH Deficiency

Abstract

GH secretion is decreased in obese subjects, whereas age-adjusted IGF-I concentrations are normal. This study was undertaken to rigorously delineate the extent of obesity [elevated body mass index (BMI)] associated with decreased somatotrope secretory function resulting in apparent adult GH deficiency. The peak GH response evoked by combined arginine (0.5 g/kg infused iv over 30 min) and GHRH (1 microg/kg iv bolus) was measured in 59 healthy male subjects with BMIs ranging from normal to obese. BMI correlated with the peak evoked GH response (Pearson r = -0.59; P < 0.01), and the percentage of subjects exhibiting an abnormal evoked GH response, i.e. less than 9 ng/ml, increased from 5% for those with a BMI less than 25 (normal), to 13% for those with a BMI of 25-26.9 (mildly overweight), to 33% for those with a BMI of 27-29.9 (moderately overweight), and to 64% for those with a BMI of 30 or more (obese). BMI is a major determinant of evoked adult GH response to provocative testing. The diagnosis of adult GH deficiency using the evoked GH response in patients with even mild BMI elevation does not accurately distinguish normal from deficient responses and may result in the erroneous classification of obese subjects as GH deficient and thus unnecessarily requiring GH replacement.

Discrepant results in the diagnosis of GH deficiency with the insulin-tolerance test and the GHRH plus arginine test in patients with traumatic brain injury

“…The GHRHC ARG test has been suggested as a safe and reliable alternative to the ITT (5) and the cut-off of 9 ng/ml is commonly used worldwide to diagnose severe GHD. Our data show a strong BMI dependence of this test in TBI patients and confirm similar findings from healthy subjects (6,7). This leads to a large proportion of obese subjects classified as GH deficient using the classical cutoff for the GHRHCARG test, even though a normal GH secretion is shown with the ITT.…”

“…They established a cut-off level of 9 ng/ml for the diagnosis of severe GHD in a lean population (5). However, recently, the GHRHCARG test has been criticized to be strongly BMI dependent and to cause false-positive results in healthy obese and overweight subjects (6,7). In TBI patients, GH levels decrease after GHRHCARG stimulation, even after exclusion of obese subjects (8).…”

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

“…In the diagnostic approach for GH deficiency obesity presents a great limitation since it is characterized by a low response to all provocative stimuli for GH secretion (26)(27)(28)(29)(30)(31)(32)(33). In obesity reduction in the half-life of GH (43) as well as a significant decrease in the production and secretion of the hormone have been reported (44).…”

Prevalence of Pituitary Hormone Dysfunction, Metabolic Syndrome, and Impaired Quality of Life in Retired Professional Football Players: A Prospective Study

“…31,32 Because of this known inverse relationship with BMI and peak GH after stimulation testing with glucagon, GHRH/arginine, and insulin tolerance testing, GHD was defined at 3 cut points, adjusted for BMI using a normal non-head-injured control cohort referred to the Dynamic Endocrine Testing Unit at the Oregon Health & Science University (Portland, OR) for assessment of possible GHD with low normal to low serum IGF-1 levels. 27,[33][34][35][36] From 119 men tested, individuals were excluded if they had a previous history of pituitary or hypothalamic tumor, other hypothalamic or pituitary disorder, pituitary surgery or irradiation, or TBI. Thirty individuals from these 119 men met the criteria and made up the control group.…”