A Prospective Evaluation of Glucagon Stimulation Test Safety in Adults With Chronic Moderate-to-Severe Traumatic Brain Injury

Abstract

Introduction: Growth hormone deficiency (GHD) is a common and clinically significant consequence of moderate-to-severe traumatic brain injury (msTBI). The glucagon stimulation test (GST) is widely used to assess growth hormone deficiency; however, the safety of GST has not been systematically evaluated in adults with chronic msTBI.

Methods: This prospective study enrolled 138 adults aged 18-65 years with chronic msTBI (≥ 1-year post-injury) from a single academic Brain Injury Center neuroendocrine registry. All participants underwent standardized GST with systematic symptom assessment at baseline and serial intervals over 240 min. Adverse events and symptoms were graded by severity using predefined clinical criteria, and participants were analysed by GHD status and by presence of any adverse event.

Results: GST was well tolerated, with no serious adverse events, test terminations, or prolonged sequelae. The most common adverse effect was nausea (30.4%), with vomiting in 9.4% of participants; antiemetics were required in 16.7% of cases. Female sex was significantly associated with nausea (p < 0.001), while age and BMI were not. Neuroglycopenic symptoms occurred in 13% of participants and were mild to moderate; only two individuals (1.5%) required oral glucose rescue, and no severe neuroglycopenia occurred. Headache (12.3%), asthenia (10.1%), and mild symptomatic hypotension (2.9%) were infrequent. Adverse events typically occurred between 60 and 210 min and resolved within the 4 h testing period. There was no significant association between GHD status, peak GH concentration, or adjusted multivariable analysis and the occurrence of adverse events. No seizures occurred, including among participants with post-traumatic epilepsy.

Conclusions: In adults with chronic msTBI, the glucagon stimulation test demonstrates a favourable safety profile with transient, non-severe adverse effects and no serious neurological or metabolic complications. These findings support GST as a safe and practical method for evaluating growth hormone deficiency in this population.

Keywords: glucagon; growth hormone deficiency; traumatic brain injury.