[Viewpoint] Should Every Patient With Traumatic Brain Injury Be Referred to an Endocrinologist?

Gianluca Aimaretti; Ezio Ghigo


Nat Clin Pract Endocrinol Metab. 2007;3(4):318-319. 

Evidence from clinical studies has demonstrated that traumatic brain injury (TBI) is often the cause of hypopituitarism. Indeed, the risk of TBI-related hypopituitarism is much greater than previously suspected.[1,2,3,4] TBI-related hypopituitarism remains underdiagnosed, however, often because of lack of awareness among the physicians most likely to see patients who might be suffering from this condition (i.e. general practitioners, endocrinologists and neurosurgeons). Given the epidemiology of TBI (~91-332 cases per 100,000 inhabitants worldwide) and the high risk of panhypopituitarism or hypopituitarism of multiple hormones after head trauma (10-15%), it is clear that thousands of individuals experience low quality of life, and possibly impaired life expectancy, because of undiagnosed hypopituitarism.[4,5] It is vital, therefore, that the medical community—particularly those physicians who take care of patients in either the acute or chronic phases of TBI—are aware of this increased risk of hypopituitarism. Awareness of the problem could aid appropriate screening of patients at risk,[1,2] and is the first step towards the introduction of endocrinologists into the multidisciplinary team involved in the care of patients with TBI.

Data in the scientific literature have confirmed the increased endocrine interest in TBI, as well as the need to conduct controlled studies in order to understand whether the hormone deficiency that manifests after TBI is partially responsible for the poor quality of life and outcome of these patients.[1,2,3] Postconcussion syndrome, and its signs and symptoms (headache, irritability, loss of memory, attention deficit, depression, fatigue, a low capacity for work, and cognitive alterations), are very common in the acute phase after TBI (~30% of all cases). The signs and symptoms of postconcussion syndrome are also similar to those of panhypopituitarism or multiple-hormone hypopituitarism, and suggest that hormone deficiencies might mimic the sequelae of TBI. Consequently, pituitary hormone deficiencies could result in suboptimal rehabilitation for patients with TBI-induced hypopituitarism.[6]

We now face a very relevant clinical and social problem—should all patients with TBI be evaluated for hypopituitarism, or can we identify a subgroup of patients who must be assessed? The onset of hypopituitarism is not related to the severity of the trauma, as measured with the Glasgow Coma Scale (GCS). The GCS assesses the patient's level of consciousness on a scale of 3 to 15. A patient with a score ≤8 is considered to be in a severe coma. Age and sex also do not correlate with TBI-related hypopituitarism.[7] The high number of pituitary deficits that occur after TBI, and the lack of a relationship with trauma severity, suggest that the first approach should be to test all patients with a history of TBI, but this strategy would exhaust national economic health resources. As there are no data available to show that diagnosis of hypopituitarism and pituitary-hormone-replacement therapy are of any benefit to patients in extreme conditions (e.g. a persistent vegetative state), it is possible that these individuals could be omitted from screening. By contrast, it has been reported that severe hypopituitarism could occur in patients who have suffered mild head trauma (GCS 13-15), which suggests the need for endocrine evaluation in this patient group.[7,8,9] Unfortunately, however, this type of trauma is often so minor that patients have no recollection of its occurrence, even after direct questioning, and only family members are able to remember the event.[10] TBI-related hypopituitarism is likely, therefore, to remain underdiagnosed in many cases of mild head trauma.

From a practical point of view, a more cost-effective approach than global screening would be to focus on patients with moderate or severe head trauma (GCS <13), as most of the published studies were performed in this patient group. Studies that examine the extent of trauma severity and the development of different forms of hypopituitarism, and which include the identification of clinical markers of disease, are still needed. In light of the currently available data, we propose that the following guidelines should be considered when deciding which patients to screen for TBI-related hypopituitarism.

Patients with an initial GCS score <13 should always be monitored and evaluated for hypopituitarism, as should those with a GCS score of 13-15 and brain imaging abnormalities such as hemorrhagic lesions (which are often seen on a CT or MRI scan). In patients who develop manifestations of acute hypopituitarism (e.g. diabetes insipidus and electrolyte abnormalities) during the immediate post-TBI period, assessment of endocrine function is mandatory. Although data show that only 3-6% of patients have persistent diabetes insipidus 3-6 months after TBI, this condition is often associated with other anterior pituitary deficits.[2,3,7] In addition, patients who develop overt symptoms of hypopituitarism many years after TBI must also be tested.

Patients with signs and symptoms of hypopituitarism, other than diabetes insipidus, 3-6 months after TBI must also be carefully evaluated as potential cases of TBI-related hypopituitarism. For example, hypogonadism manifests as menstrual disturbances in women and decreased libido and impotence in men. Patients who develop TBI-related metabolic alterations (i.e. secondary metabolic syndrome with weight gain, lipid abnormalities, and insulin resistance) could have undiagnosed growth hormone deficiency and might benefit from replacement therapy. Children and adolescents with a history of moderate or severe TBI should always be considered for screening of pituitary insufficiency. Clinicians and pediatricians must also be made aware that the burden of hypopituitarism on childhood development could be extensive, and might lead to reduced height, slow growth rate, and pubertal retardation.

With regard to the timing of endocrine evaluation, it was proposed that patients with TBI should be prospectively evaluated 3-6 months and 12 months after the injury.[1,2,3,7] This approach would be sufficient to diagnose chronic alterations in pituitary function; however, it must be emphasized that the status of pituitary function immediately after brain injury is not yet known and that transient changes in pituitary function can occur. The extent to which pituitary function can be impaired in the acute phase after brain injury, and how much this impairment affects the chances of survival and recovery, are questions that still await answers.

In conclusion, although TBI is associated with a high risk of hypopituitarism, it is neither practical nor cost-effective to evaluate pituitary function in all patients after head trauma. Until further data become available, therefore, we currently recommend a case-finding approach to select patients for screening of TBI-related hypopituitarism.

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