Insulin Tolerance Test in Adult GH Deficiency: An Exploratory Study Deriving BMI-Dependent Cut-Offs Using a Clinical Reference Standard

Abstract

Background: The diagnosis of adult growth hormone (GH) deficiency (GHD) relies on demonstrating a reduced GH response to stimulation tests. Excess body weight, an increasingly prevalent condition, is associated with a blunted GH response to all types of stimulation tests. Therefore, establishing body mass index (BMI)-dependent cut-offs is essential for accurate interpretation. This study aimed to identify BMI-specific diagnostic thresholds for the insulin tolerance test (ITT), using residual pituitary function as the clinical gold standard. Methods: We retrospectively analyzed 105 patients with hypothalamic-pituitary disorders who underwent ITT. GHD was defined by the presence of at least three pituitary hormone deficiencies, while preserved somatotropic function was defined by the absence of other pituitary deficits and an insulin-like growth factor-I (IGF-I) standard deviation score ≥ 0. Receiver operating characteristic (ROC) curve analysis was used to determine optimal BMI-stratified cut-offs, defined as those maximizing sensitivity (SE) and specificity (SP). Results: The optimal GH cut-off was 2.8 μg/L for patients with normal weight (SE 84.6%, SP 97.4%) and those with overweight (SE 100%, SP 92.3%), and 2.1 μg/L for patients with obesity (SE 88.2%, SP 87.5%). The area under the ROC curve was 0.968, 0.957, and 0.897 for patients with normal weight, overweight, and obesity, respectively. Conclusions: This is the first study to define GH diagnostic thresholds for the ITT according to BMI, using a clinical definition of GHD as reference. More restrictive cut-offs in patients with obesity are needed to avoid GHD overdiagnosis and potential overtreatment. These findings should be considered hypothesis-generating and require prospective external validation before routine clinical implementation.