Identifying Growth Hormone Deficiency in Brain-Injured Patients: The Quality of Life Scale-99

Traumatic brain injury (TBI) is frequently associated with hypopituitarism. The hypothalamic-pituitary axis appears to be susceptible to the same forces that cause injury to the parenchyma of the brain. Following even a mild TBI (mTBI), patients may suffer transient or permanent decreases in anterior pituitary hormones, including somatotropin (growth hormone [GH]), gonadotropins (luteinizing hormone and follicle-stimulating hormone), thyrotropin, and adrenocorticotropic hormone, with the most frequent long-term deficiency being GH deficiency (GHD). GHD is common after mTBI and is often the cause of persistent post-concussive symptoms a year or more post-injury. GHD is known to cause physical and cognitive fatigue, cognitive inefficiency, metabolic changes, and a range of psychological symptoms. Confusing the picture is that some symptoms of GHD are also common to brain injury itself. To facilitate the detection of GHD when comorbid with TBI, we utilized a new symptom inventory, the Quality-of-Life Scale-99 (QoLS-99), and administered it to a cohort of chronic TBI subjects with and without GHD, distinguished using the insulin tolerance test (ITT). Between 2018 and 2023, 371 patients completed the QoLS-99, of which 263 underwent GH testing with the ITT. Of these 263 patients, 136 (52%) were diagnosed with GHD. A retrospective comparison of QoLS-99 scores found that loss of libido (p < 0.006), a reliance on sleep aids (p < 0.011), and feeling overweight (p < 0.015) were the strongest univariate predictors of GHD. Most survey items did not elicit a significant difference in response between the GHD groups, and for those that did, effect sizes were mild to moderate. Still, initial findings demonstrate strong predictive value in a subset of survey items (i.e., GHD symptoms) that are most discriminating in the sample of patients with TBI. A multivariate prediction model using this subset of questions was able to differentiate GHD status in patients with TBI, correctly identifying 88% of GHD cases with a 37% false positive rate. Based on these findings, we recommend that clinicians inquire about libido, insomnia, and body image as potential markers for GHD. Furthermore, given the amenability of patients with GHD to growth hormone replacement therapy, we strongly encourage clinicians and basic scientists to develop interventions for the large and underserved population of patients with TBI with comorbid GHD.