Prospective study of hypothalamo-hypophyseal dysfunction in children and adolescents following traumatic brain injury

Abstract

Background and Aims.Retrospective studies of TBI have found a neuroendocrine dysfunction following traumatic brain injury in 23 to 60% of adults and 15 to 21% of children. Our aims were to determine the prevalence of hypothalamo-hypophyseal dysfunction in children following brain injury, assess its relationship to the type of injury and the course of the acute post-traumatic phase. Patients and Methods. Body development (growth, pubertal development, and skeletal maturity) were evaluated in 58 patients (21 girls) after a brain injury rated 3 to 12 on the Glasgow Coma Scale (GCS). The patients underwent standard endocrine tests -TSH, fT4, IGF-1, PRL, morning cortisol, FSH, LH, and testosterone in boys and estradiol in girls -in the early post-traumatic period (2 to 14 days; T0) and at 3, 6, and 12 months after the injury (T3, T6, and T12). Dynamic tests were carried out in patients with abnormalities in their clinical examination and/or laboratory results. An MRI was performed on all patients at T12. Results. The median age at the time of injury was 11.3 (0.5 to 18.7) years. Of the 58 patients, 23 had GCS < 8, corresponding to severe brain injury. At T0, diabetes insipidus (DI) was diagnosed in 12 patients, and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in 4 patients. Frequent hormonal changes simulated central hypothyroidism (in 45% of patients) and hypogonadotropic hypogonadism (in 25% of adolescents who were already pubertal at the time of injury > Tanner II). Examination at T3 (n = 58) confirmed a combined pituitary hormone deficiency in two boys and DI in another one. At T6 (n = 49), hormonal dysfunctions were diagnosed in two boys (precocious puberty and growth hormone deficiency). At T12 (n = 39), a new endocrine dysfunction was diagnosed in five patients (growth hormone deficiency in two, hypogonadotropic hypogonadism in two, and in one patient, already diagnosed with a growth hormone deficiency, central hypothyroidism, as well). Brain MRI revealed an empty sella in two patients with growth hormone deficiency. Patients with GCS < 8 had more symptoms of SIADH or DI in the early post-traumatic period 11/23 vs. patients with GCS of 8 to 13 (4/35), and more frequent hormonal disorder (6/23) than individuals with moderate trauma (3/35), P = 0.0135. The incidence of endocrine dysfunction at T0 significantly correlated with the severity of injury (P = 0.05), but it was not an indicator for the development of a late hormonal disorder. Conclusion. Within a year after injury, a hormonal disorder was found in 17.6% of the patients. Neuroendocrine dysfunction as a late consequence of craniocerebral trauma in children and adolescents was less frequent than in adults. Risk factors for its development are the gravity of the injury, brain scan pathology, and possibly the development of DI, SIADH, or CSWS in the acute post-traumatic phase.

High frequency of empty sella, with gender differences, in the early neuroradiology evaluation of patients with traumatic brain injury. A prospective study

“…Secondary empty sella may be caused by pituitary adenomas undergoing spontaneous necrosis (ischemia or hemorrhage), by infective, autoimmune, and traumatic causes, or by radiotherapy, drugs, and surgery [17]. Studies with evaluation performed in the early phase of TBI are detailed in Table 8 [12], [18], [19], [20], [21], [22], [23], [24]. The frequency of empty sella depends on the setting.…”

Elucidating opportunities and pitfalls in the treatment of experimental traumatic brain injury to optimize and facilitate clinical translation

“…Clinical studies in patients with mild to severe TBI report neuroendocrine abnormalities affecting corticotropin, growth hormone, gonadotropin, thyrotropin, prolactin, and vasopressin (Behan et al, 2008; Javed et al, 2015). Hypothalamohypophyseal dysfunction has been reported in 17% of patients with a severe trauma, rated 3 to 12 on the GCS, as a late consequence of craniocerebral trauma, and is more frequent in adults and less in children and adolescents (Krahulik et al, 2016). Current recommendations involve screening all moderate to severe TBI patients beginning with testing for hypocortisolism with a morning cortisol level within seven days post injury as hypopituitarism treatment may improve emotional and cognitive function in these patients (Renner, 2015).…”

Anterior Pituitary Hormonal Disturbances in Patients Suffering with Traumatic Brain Injury

“…observed the incidence of neuroendocrine dysfunction following traumatic brain injury in 23%–60% of adults and 15%–21% of children in a respective analysis. [5] Krahulik et al . analyzed growth, pubertal development, and skeletal maturity evaluation in 58 patients following traumatic brain injury within the age range of 0.5–18.7 years.…”

“…The incidence of endocrine dysfunction at initial evaluation significantly correlated with the injury severity; however, it was not related to subsequent development of a late hormonal dysfunction. [5] In the 1 st year following head injury, the hormonal disorder was observed in 17.6% of the cases; however, it was less frequent in children and adolescents than compared to adults, and risk factors include severity of the craniocerebral injury, finding on neuroimaging, and the presence of traumatic intracranial mass effect. [5]…”

“…[1] First, the sample size comprising of 24 children is comparatively much smaller, and small cohort size may be a factor for incongruency of result compared to other published literature. [456] Second, large number of cases, i.e., 58.3% children, represented to suffer mild head injury and more so these cases might be having Glasgow coma scale of 15/15 after sustaining head injury, a may be a factor for comparatively very low incidence of hormonal dysfunction observed in the study by Aylanç et al . [1] and further only a miniscule of cases, i.e., 4.2% sustained were representative of sustaining severe head injury.…”