Hypopituitarism in Pediatric Survivors of Inflicted Traumatic Brain Injury

Abstract

Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n = 14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population ( p < 0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

Pituitary dysfunction after traumatic brain injury: are there definitive data in children?

“…As Auble et al 30 noted, this is significantly higher than the estimated prevalence of 2.5% in the general population. The differences between paediatric and adult prevalence may be explained, in addition to the methodological differences in study design, by the mechanism of TBI as we detail above.…”

“…The prevalence of abnormal GH tests in the literature is variable, ranging from 4% to 15% in those studies in which patients were assessed based on clinical criteria,20 22 23 to 21–31% when provocative testing was performed regardless of the clinical status 21 25–28 30. There are some additional differences between studies, for example, their prospective or retrospective design, and the use of different tests and different cut-off criteria.…”

“…Heather et al ,27 Auble et al 30 and Salomón-Estébanez et al 31 restricted studies to those patients with structural abnormalities after TBI. Another difference was the rate of inclusion reported by different studies, ranging between 20% and 70%, which may obviously influence the estimation of the prevalence of hypopituitarism 20–31…”

Post‐traumatic hypopituitarism: report of a child case

“…There is no definite recommendation that routine endocrine evaluation should be carried out following TBI 13, 14. Auble et al .…”

Traumatic brain injury and neuro-endocrine disruption: Medical and psychosocial rehabilitation

“…TBI has been linked to neuroendocrine insufficiencies mediated by pituitary, such as: thyroid and adrenal functioning (Tsargarakis, Tzanela, & Dimopoulou, 2005), diabetes insipidus (Griffin, Hartley & Crow, 1976), growth hormone deficiencies (Lorenzo et al, 2006;Lopez et al, 1992), and hyperprolactinemia (Bondanelli et al, 2004). The percentage of individuals affected is high; 35-40% of individuals who sustained a TBI are estimated to have some degree of hypopituitarism, with incidence estimates of over 80% of children and adults with severe brain injuries (Auble et al, 2013;Hannon et al, 2013;Popovic, Aimaretti, Casanueva, & Ghigo, 2005;Rose & Auble, 2012). While there is at least one multi-center study that found no association between TBI and endocrine abnormalities, these findings appear to be the outlier (Kokshoorn et al, 2011).…”