Virginia Via Research Day Book 2026

Faculty Research Clinical

01 DIAGNOSTIC ACCURACY OF THE GLUCAGON STIMULATION TEST FOR GROWTH HORMONE DEFICIENCY IN ADULTS WITH MODERATE TO SEVERE TRAUMATIC BRAIN INJURY

Context: Traumatic brain injury (TBI) is a significant cause of anterior pituitary dysfunction, with growth hormone deficiency (GHD) being a common long-term endocrine sequela. GHD adversely affects quality of life, cognition, and physical function, making accurate diagnosis and timely intervention critical. The glucagon stimulation test (GST) is frequently used to assess GHD in adults with TBI. While expert consensus supports a single GST for diagnosis, some insurers require a second confirmatory test, potentially delaying treatment. No prior studies have evaluated the sensitivity and specificity of the GST for diagnosing GHD specifically in adults with moderate-to-severe TBI (msTBI). Objective: To assess the diagnostic performance of the GST for GHD in adults with msTBI and determine whether a second confirmatory test is necessary. Methods: A prospective cohort of 100 adults (aged 18-65) with msTBI was enrolled. Inclusion criteria were best Glasgow Coma Scale (GCS) ≤ 12 within 24 hours post-injury, post-traumatic amnesia VCOM-Virginia, Blacksburg, Virginia Virginia Tech-Carilion School of Medicine, Roanoke, Virginia Carilion Clinic Brain Injury Center, Roanoke, Virginia Justin Weppner, DO; Jennifer Bath, RN; Marian Pedreira, OMS-IV Corresponding author: jlweppner@carilionclinic.org

>24 hours, or unconsciousness >30 minutes, and at least one-year post-injury to allow for pituitary recovery. All participants had an Insulin-like Growth Factor-1 (IGF-1) z-score < 0, indicating high pre-test probability for GHD. Comprehensive neuroendocrine assessment and correction of other hormone deficiencies preceded dynamic testing. Exclusion criteria included three or more hormone deficiencies with IGF-1 z-score < -2, cognitive impairment precluding consent, recent pituitary surgery, active acromegaly, pheochromocytoma, significant hepatic or renal dysfunction, recent cancer, uncontrolled hypertension, severe illness, recent GH therapy, and contraindications to insulin tolerance testing (ITT). The GST was performed using standardized dosing and serial blood sampling for GH and glucose. A second GST was administered 7-28 days later. Discordant results prompted a confirmatory ITT. Diagnostic cutoffs for GHD were peak GH ≤ 3.0 µg/L (BMI < 30 kg/m²) or ≤ 1.0 µg/L (BMI > 30 kg/m²). Statistical analyses included t-tests and receiver operating characteristic (ROC) curve analyses.

Results: Participants had a mean age of 42.6 years and mean BMI of 28.3 kg/m². The mean IGF-1 z-score was -1.16. There were no significant demographic or injury-related differences between GHD and non GHD groups. IGF-1 z-scores were significantly lower in the GHD group, but IGF-1 alone showed only fair discriminatory power (AUC = 0.711). The GST demonstrated excellent diagnostic accuracy, with sensitivity of 96.3%, specificity of 98.6%, and AUC of 0.975. Conclusions: The GST provides excellent diagnostic accuracy for GHD in adults with msTBI and low IGF-1 at least one-year post-injury. A single GST is sufficient for diagnosis in this population, and routine use of a second confirmatory test is not supported. Adoption of this approach may reduce unnecessary delays and healthcare costs. Further validation in multi center cohorts is warranted. This study was approved by the Carilion Clinic IRB, protocol number IRB-24-1931.

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168 Edward Via College of Osteopathic Medicine (VCOM)