Cortisol Dynamics, Quality of Life, and Fatigue following Traumatic Brain Injury in Childhood

Abstract

<b><i>Introduction:</i></b> Traumatic brain injury (TBI) is a leading cause of acquired neurological morbidity. The prevalence of post-traumatic hypopituitarism and associated morbidity after childhood TBI is unclear. Our study investigated long-term hypothalamus-pituitary-adrenal (HPA) axis function, in a prospective childhood TBI and control cohort, using measures of cortisol/cortisone secretion (physiological and stimulated), HPA axis feedback, and exploring associations with fatigue, depression, and quality of life (QoL) outcomes. <b><i>Methods:</i></b> All TBI participants had data concerning severity and mechanism of TBI. All groups had clinical assessment, pituitary/brain MRI, questionnaire measures of QoL, fatigue, depression, and salivary cortisone profiles including dexamethasone suppression test. In addition, participants with moderate/severe TBI had ethical approval for baseline endocrine blood tests, overnight 12-h venous sampling of cortisol and growth hormone, and stimulated HPA axis evaluation with an insulin tolerance test (ITT). <b><i>Results:</i></b> Seventy-two participants with moderate/severe (<i>n</i> = 31, age 19.8 ± 4.2 years) or mild TBI (<i>n</i> = 24, age 17.8 ± 5.1 years) and matched controls (<i>n</i> = 17, age 18.5 ± 5.5 years) took part. Time post-TBI was 6.8–10.8 years. Baseline endocrine tests confirmed normal thyroid and posterior pituitary function. One female with moderate/severe TBI had hypogonadism. Pituitary neuroimaging was normal in all participants. In 2/25 ITT and 9/22 overnight serum profiles, peak cortisol was &lt;500 nmol/L. The two participants with suboptimal ITT cortisol response (392 and 483 nmol/L) also had low peak spontaneous serum levels (227 and 447 nmol/L, respectively). Salivary cortisone profiles showed preservation of HPA axis circadian rhythm and suppression with dexamethasone in all but one TBI participant. TBI participants had higher morning salivary cortisone levels compared to controls. Fatigue was reported by 20/46 TBI participants but only 1/14 controls. Fatigue was not associated with stimulated (ITT) or spontaneous (overnight profile) cortisol; however, one TBI participant with severe fatigue had a suboptimal ITT cortisol response. Specific QoL attributes of health state (cognition, memory) were impaired in TBI participants compared to controls. <b><i>Conclusion:</i></b> Although not as prevalent as previously reported, HPA axis dysfunction does occur in survivors of childhood TBI, confirming the need for endocrine surveillance. However, in most of our paediatric TBI survivors assessed 7–11 years post-TBI, HPA function and circadian rhythmicity were preserved or had recovered. Chronic fatigue is a common concern post-TBI, but in the majority, it is not associated with frank HPA axis dysfunction. Morning salivary cortisone levels were higher in TBI survivors (who have a high prevalence of fatigue) compared to healthy controls, despite the recognised association of chronic fatigue with cortisol hyposecretion.