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Cited by 31Traumatic Brain Injury and Neurovascular DisturbancesPituitary Gland Disorders and TreatmentsTraumatic Brain Injury Research

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

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Krahulik, David, Aleksijevic, Darina, Smolka, Vratislav, Klaskova, Eva, Venhacova, Petra, Vaverka, Miroslav, Mihal, Vladimir, Zapletalova, Jirina·2017·Biomedical Papers
DOI 10.5507/bp.2016.047
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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.

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  • A study of 58 children and adolescents assessed at 3, 6, and 12 months after TBI found new hormonal deficiencies in 5 subjects at 12 months that were not present at 3 and 6 months.

    “More recently, a study of 58 children and adolescents assessed at 3, 6, and 12 months after TBI found new hormonal deficiencies in 5 subjects at 12 months that were not present at 3 and 6 months [19].”

    From Neuroendocrine Disruptions Following Head Injury (2023) · cites this paper as [19]

    The Methods and Results describe 58 children and assessments at 3, 6, and 12 months after TBI. The Results report two GH deficiencies and two cases of partial hypogonadotropic hypogonadism at 12 months, plus central hypothyroidism in a boy who already had GH deficiency at 6 months. Thus the paper does not support five subjects with new deficiencies absent at both earlier assessments. (LLM, conf=0.90)

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  • Deficiencies termed 'chronic' after 3 months do not always persist and may improve over time.

    “While deficiencies are often termed 'chronic' after 3 months, they do not always persist [17]. Deficiencies, even those diagnosed in the chronic post-TBI period, may improve over time [11, 18-21].”

    From Neuroendocrine Disruptions Following Head Injury (2023) · cites this paper as [19]

    The Results and Discussion report that most hormonal changes in the acute post-TBI phase were transient, supporting the general point that deficiencies need not persist. They do not show that a deficiency diagnosed after three months subsequently improved; the Results instead describe persistent or newly identified dysfunction at later visits. The source therefore supports improvement over time only for acute-phase changes, not the claim’s chronic-period qualifier (page numbers unavailable in our copy). (LLM, conf=0.78)

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Research works printed but not linked: 9

  1. Masson F, Salmi LR, Maurette P. Characteristics of head trauma in children: epidemiology and 5-years follow up. Arch Pediatr 1996;3:651-60.
  2. Cyran E. Hypophysisenschadigung durch Schadelbasis fracture. Dtsch Med Wochenschr 1918;44:1261-70.
  3. Escamilla RF, Lisser H. Simmonds disease. J Clin Endocrinol Metab 1942;2:65-96.
  4. Harper CG, Doyle D, Hume AJ, Graham DI. Analysis of abnormalities in pituitary gland in nonmissile head injury: study of 100 consecu- tive cases. J of Clin Pathol 1986; 39:769-73.
  5. Woolf PD. Hormonal response to trauma. Crit Care Med 1992;20:216- 26.
  6. Krahulík D, Zapletalová J, Fryšák Z, Vaverka M. Dysfunction of hy- pothalamo-hypophyseal axis after traumatic brain injury in adults. J Neurosurg 2010;113(3):581-4.
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  8. Aleksijevic D , Zapletalová J, Smolka V, Klásková E, Wiedermann J, Krahulík D, Vaverka M, Fryšák Z. Neuroendokrinní dysfunkce u dětí a dospívajících po úrazu mozku. Cesk Slov Neurol N 2010;106(4):409- 14.
  9. Bláha P, Vígnerová J, Riedlová J, Kobzová J, Krejčovský L. VI. Celostátní antropologický výzkum dětí a mládeže 2001 (National anthropo- logical research of children and adolescents 2001). Čes-slov Pediat 2003;58(12):766-70.

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Authors
Krahulik, D., Aleksijevic, D., Smolka, V., Klaskova, E., Venhacova, P., Vaverka, M., Mihal, V., & Zapletalova, J.
Affiliations
University Hospital Olomouc (CZ)
Venue
Biomedical Papers
Publisher
Palacky University Olomouc
Published
2017-03-27
Volume
161
Issue
1
Pages
80-85
ISSN
  • 1213-8118 (ISSN-L)
  • 1804-7521
DOI
10.5507/bp.2016.047
OpenAlex
W2521653571
Cited by
31
References
23
Citations by year
2026: 4 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 4 · 2012: 1
FWCI
2.51
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Biomedical Papers (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
traumatic brain injury, pediatric brain injury, adolescents, diabetes insipidus, syndrome of inappropriate antidiuretic hormone secretion, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency, precocious puberty, combined pituitary hormone deficiency, neuroendocrine dysfunction, hypothalamic injury
MeSH terms
Brain Injuries, Traumatic, Adolescent, Child, Child, Preschool, Diabetes Insipidus, Female, Humans, Hypogonadism, Hypopituitarism, Hypothalamic Diseases, Hypothalamic Hormones, Hypothalamo-Hypophyseal System, Hypothyroidism, Inappropriate ADH Syndrome, Magnetic Resonance Imaging, Male, Prospective Studies, Puberty, Precocious, Risk Factors, Time Factors, Human Growth Hormone

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