Protocol 1: To determine whether pituitary dysfunction is present at intermediate duration of follow-up after traumatic brain injuryProtocol 2: To determine whether injury to brain tissue that explains traumatic brain injury-induced pituitary…
ID
Source
Brief title
Condition
- Other condition
- Hypothalamus and pituitary gland disorders
- Structural brain disorders
Synonym
Health condition
traumatologische aandoeningen
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Protocol 1: Proportion of TBI patients who display a pituitary dysfunction
Protocol 2:
a) Difference in volume of pituitary gland and hypothalamus
b) Difference in structural connectivity between hypothalamus and hypothetical
projections
c) Differences in functional connectivity in the resting state
Protocol 3: Difference in functioning in daily living as expressed by
GOS-E-score
Secondary outcome
Protocol 1:
a) Proportion of patients with a history of trauma without head injury that
have pituitary dysfunction
b) Difference in functioning in daily living as expressed by GOS-E-score
c) Difference in abnormalities going with classical pituitary dysfunction, as
assessed by a questionnaire, physical examination and cardiovascular analysis
d) Difference in scores on questionnaires on quality of life, physical,
cognitive and psychological functioning and fatigue
Protocol 2: Difference in structural cerebral defects
Protocol 3:
a) Difference in scores on questionnaires on quality of life, physical,
cognitive and psychological functioning and fatigue
b) Difference in scores on neuropsychological evaluation
c) Difference in presence of biochemical pituitary dysfunction
Background summary
Traumatic brain injury (TBI) yearly hits a large number of mainly young people.
The consequences (i.e. long lasting psychocognitive and somatic limitations:
posttraumatic complaints) are a large burden to patient and society. These
posttraumatic complaints show hitherto unrecognized striking similarities to
the signs and symptoms that occur in neuroendocrine disorders. Recent studies
suggest that the prevalence of anterior pituitary dysfunction following head
injury is approximately 30% of all moderate and severe TBI patients. So far
sparse research has been carried out on patients with mild TBI and at
intermediate follow-up (1 to 2 years), and there was a selection bias. It is
not elucidated yet whether the observed pituitary dysfunction related to TBI is
clinically displayed.
Actually it is assumed that pituitary ischemia is a sole pathophysiological
mechanism through which TBI causes disruption of pituitary function. The
involvement of the distinctive pituitary hormonal axes and the reversible
pattern of pituitary dysfunction in some patients argue for other
pathophysiological mechanisms. An additional mechanism could be damage to
structures projecting on the hypothalamus. In that case, plasticity of brain
function and regenerative capacity after damage of brain tissue could explain
the observed reversibility of pituitary dysfunction.
Another approach to predict impaired recovery after TBI is the analysis of
genetic polymorphisms. TBI disturbs the functional equilibrium in the local
tissue of the brain, impairing recovery. Optimal adaptation of neuro-endocrine
balances is imperative for restoration of this equilibrium. Genetic
polymorphisms may account for differences in the expression of the stress
response of individual hormonal axes and the capacity to adapt to tissue damage
associated with TBI.
Study objective
Protocol 1: To determine whether pituitary dysfunction is present at
intermediate duration of follow-up after traumatic brain injury
Protocol 2: To determine whether injury to brain tissue that explains traumatic
brain injury-induced pituitary dysfunction, is localized in the
hypothalamo-pituitary zone and/or in the afferent (especially cortical)
projections to the hypothalamus
Protocol 3: To evaluate whether polymorphisms in genes, associated with the
stress response of distinctive pituitary hormonal axes, are related to clinical
outcome after traumatic brain injury
Study design
Protocol 1 and 3: explorative cohort study
Protocol 2: observational study
Study burden and risks
Post traumatic complaints and psychological/physical limitations after TBI are
a large burden to patiënt and society. New methods of prevention and treatment
of these limitations are therefore important. Once insufficiency of the
pituitary is diagnosed, it is easily treatable by hormone substitution.
Actually, it has not been elucidated yet whether pituitary dysfunction could
explain a major part of the clinic that is found in patients with a history of
TBI at intermediate follow-up. Most factors limiting recovery, such as a
disturbed cerebral metabolism in the acute phase, cannot be influenced. Hormone
deficiencies in contrast can be treated within regular health care by hormone
substitution therapy. A better understanding of the pathophysiological
mechanisms that are involved in TBI-associated pituitary insufficiency could
give rise to development of new intramural and transmural approaches in the
first months after trauma with adaptations in the revalidation program.
We expect that in the group of patients whose expression of will is impaired as
a consequence of their brain injury, the prevalence of pituitary dysfunction is
highest, as their brain injury on the average is more serious. As their brain
injury on the average is more serious, a study population excluding patients
whose expression of will is impaired as a consequence of their brain injury,
would not be representative for the total group of patients with moderate or
severe TBI. The results of such a study would not be generalisable. Also we
expect that pituitary dysfunction may contribute to maintenance of the
impairment of expression of will, as we expect pituitary dysfunction to
contribute to an impairment of psychological and cognitive recovery after TBI.
Reinier postlaan 4
6500 HB Nijmegen
Nederland
Reinier postlaan 4
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
1. All patients who visit the emergency department with a mild, a moderate or a severe traumatic brain injury. (Mild traumatic brain injury is defined as a history of impact to the head and a Glasgow Coma Scale score (GCS) 13-15 at entry in the emergency room, moderate traumatic brain injury is defined as a GCS 9-12 at entry in the emergency room, and severe traumatic brain injury is defined as a GCS <= 8 at entry in the emergency room)
2. Initial trauma occurred less than 24 hours before visiting the Emergency Department.
3. Age >= 18 years and <= 65 years
Exclusion criteria
1. Age > 65 years or < 18 years
2. No oral or written informed consent by patient or proxy
3. Pre-existent neuro-endocrine disorder
4. Instable infiltrative disease in the hypothalamus/pituitary region (eg sarcoidosis, tumour metastasis)
5. BMI >30 kg/m2
6. Pregnancy or wish for pregnancy during the study period women, lactation
7. Co-existent disease with decreased life expectancy, especially active malignant tumor
8. Chronic alcohol or drug abuse
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL14996.091.06 |