Neuroendocrine consequences of childhood traumatic brain injury

OBJECTIVES: 1) To determine the prevalence, aetiology and clinical significance of pituitary dysfunction after moderate or severe childhood traumatic brain injury (TBI); and 2) to examine its impact on quality of life (QoL) and body composition.SUBJECTS: Retrospective observational study of 33 survivors of accidental TBI (27 males) and two of inflicted TBI (both males). Accidental TBI group: mean (SD) age at study was 13.4y (3.7y) and interval since injury, 4.1y (1.6y). King's Outcome Scale for Childhood Head Injury (KOSCHI) rating: 15 good recovery, 16 moderate disability, 2 severe disability. Inflicted TBI group: ages at study were 5.0 and 3.7 years at 4.9 and 3.3 years post-injury with good recovery and moderate disability respectively.METHODS: Early morning urine samples were obtained for osmolality. Basal hormone evaluation (0800-1 OOOh) was followed by the gonadotropin-relasing hormone (GnRH) and insulin tolerance (ITT, n=26) or glucagon tests (ifprevious seizures, n=9). Subjects were not primed. Body composition was evaluated using bioelectrical impedance analysis. Standardised quality of life (QoL) questionnaires were completed. Head injury details were extracted from patient records.RESULTS: There were no abnormal findings in the two survivors of inflicted TBI. Among the accidental TBI group, no subject had clinical evidence of impaired growth: mean height standard deviation score (SDS) was +0.5 (range -1.6 to +3.0 SD). Median peak growth hormone (GH) response to stimulation was 7.9 pg/L. Six peri-pubertal males had suboptimal GH responses (<5 pg/L). Their height SDS at study ranged from -1.5 to +1.4; one had slow growth on follow-up. GH response was borderline low in one post-pubertal male (3.2 pg/L).Median peak Cortisol responses were 538 nmol/L (ITT) and 562 nmol/L (glucagon). 9/25 (ITT) and 2/8 (glucagon) subjects had sub-optimal responses. In two cases (one ITT, one glucagon test), basal Cortisol levels were high (624 and 722 nmol/L). For the rest, in 6/9, further testing or no action was advised; in 3/9, steroid cover was recommended for moderate or severe illness or injury. None required routine glucocorticoid replacement. No subject had diabetes insipidus. Thyroid function, IGF-I, oestradiol/testosterone, and baseline and GnRH-stimulated LH and FSH were appropriate for age, sex and pubertal stage. One male was prolactin deficient (<50 mU/L).Abnormal endocrine findings were unrelated to severity of TBI, nature of primary or secondary brain injury, or KOSCHI rating. No significant difference in QoL was observed between those with normal or abnormal pituitary function <16y. QoL was poorer in the post-pubertal male with GH deficiency than in other subjects >16y.CONCLUSIONS: Whilst mild pituitary 'dysfunction' was common (39%), no unequivocal clinically significant endocrinopathies were found, although the GH and hypothalamopituitary-adrenal axes may be vulnerable