Endocrine Aspects of The Traumatic Brain Injury: Medico-Legal Implications

Introduction

Traumatic brain injury (TBI) is a very common injury, particularly among children and young adults. The commonest causes of TBI are: falls (28%), traffic accidents (20%), struck by/against (20%), assaults (12%).

It is well known that TBI could be associated with various pituitary hormone deficiencies in more than 25% of patients. Among multiple pituitary deficits, the most common ones are: growth hormone (GH) deficiency present in approximately 25% of patients, adrenocorticotropin hormone (ACTH) deficiency present in approximately 20% of patients and gonadotrophin (LH and FSH) deficiency in approximately 12%. In older age, TBI severity and skull fractures appear to be risk factors for pituitary disorders.

The signs and symptoms associated with pituitary hormone deficiencies (hypopituitarism) are non- specific and often mimic the sequellae of TBI. Because of this, pituitary hormone deficiencies could result in sub-optimal rehabilitation for patients with TBI-induced hypopituitarism. Fatigue is a major symptom and it is also a major symptom of TBI.

It is often difficult to differentiate to what extent the symptoms like memory loss, decreased concentration, mood disturbances, increased anxiety and depression, irritability, insomnia and a sense of social isolation are the result of TBI itself and to what extent hypopituitarism might be contributing to these symptoms.

Background

The pituitary gland is situated at the base of the brain and connected to the hypothalamus (part of the brain) with numerous nerves and a delicate and fragile network of blood vessels. The hypothalamus controls the production and secretion of the pituitary hormones by releasing substances into those fragile blood vessels. The pituitary gland in turn, secretes hormones which control other endocrine glands (adrenal, thyroid, gonads). Because of their anatomical position and delicate network of blood vessels, both the hypothalamus and the pituitary are vulnerable structures and at risk of injury with any severe head trauma. Pituitary dysfunction as a result of TBI may be partial (deficit of one or more pituitary hormones – partial hypopituitarism) or complete (deficit of all pituitary hormones – panhypopituitarism). A systemic review which examined 14 studies including over 1000 patients showed the prevalence of endocrine dysfunction in 15% to 68% of TBI patients (severe 35.3%; moderate 10.9% and mild 16.8%).

Pituitary hormone deficiencies

Growth hormone (GH) deficiency is the most common pituitary hormone deficit found at one and three years after TBI and could often be found as an isolated pituitary hormone deficiency. GH deficiency resembles post-traumatic stress disorder including profound fatigue, anxiety, depression, irritability, sleep disturbance, sexual dysfunction, cognitive deficiencies and decreased quality of life. Evaluation for GH deficiency should be considered during the rehabilitation phase after TBI.

ACTH deficiency is the second most common hormone deficiency after TBI. This results in low cortisol levels (secondary adrenal insufficiency) or in some cases only in inadequate cortisol responses to stimulatory tests (cortisol level of 500nmol/L or less in response to Synacthen stimulation). In case of the latter cortisol values are in the normal range but the body’s ability to respond adequately to stress is impaired. Of all the pituitary hormones, only the loss of ACTH is likely to be lethal, particularly during various stresses such as infection, surgery or major trauma.

Some 80% of patients have secondary hypogonadism immediately after TBI but gonadotrophin deficiency was the most likely to recover completely in most patients by six months after injury.

TSH deficiency is relatively rare disorder after TBI and results in underactive thyroid (secondary hypothyroidism).

In a large cohort, 21.6% of patients developed diabetes insipidus in the immediate post-TBI period whereas only 6.9% had permanent diabetes insipidus (more than half had partial diabetes insipidus). Patients who developed permanent diabetes insipidus were more likely to have lower GCS scores, indicating more severe brain injury.

Prognosis

‍There is a general trend toward improvement in pituitary function with time, but in some cases, new deficiencies may evolve later on. Most of earlier studies reported a transient pituitary dysfunction recovering within the first year after TBI. Twelve months after TBI nearly 60% show fully normal pituitary function. A recent systemic review which examined 66 studies with over 5000 patients showed that approximately 30% of TBI patients have persistent anterior pituitary disorders.

Conclusion

Deficiency of one or more pituitary hormones as a result of TBI is relatively recently recognized entity. Although there are several studies published over the past few years, most of them relate to patients assessed immediately after TBI, six or 12 months later. Only one prospective study followed up the same group of patients one and three years after TBI. The authors reported significant recovery in pituitary function, so that only a relatively small proportion of those who had deficiency at one year still had deficiency after three years. It is not known at present what happens beyond three years or whether the pituitary function recovery reaches a plateau around that time.

In the ideal world everybody who had TBI should have assessment of pituitary function but this has serious financial implications and is unlikely to happen in an overstrained NHS. From the medico-legal point of view, a history of skull fracture and an initial Glasgow Coma Score of less than 13 should always justify evaluation for possible hypopituitarism. Investigation should be undertaken by an endocrinologist with experience in pituitary disorders.

Once diagnosed with pituitary deficiency, patients could be treated by appropriate hormone replacement therapy which in some cases could be lifesaving (ACTH deficiency) or in many cases significantly improve the quality of life (growth hormone deficiency).

Selected references:

‍Aimaretti G & Ghigo E: Should every patient with traumatic brain injury be referred to an endocrinologist? Nature Clinical Practice Endocrinology & Metabolism 2007; 3: 318-319

Ghigo E et al: Consensus guidelines on screening for hypopituitarism following traumatic brain injury. Brain Injury 2005; 19: 711-724

Klose M et al: Prevalence and predictive factors of post- traumatic hypopituitarism, Clin Endocrinol, 2007; 67: 193-201 Personnier C et al: Prevalence of pituitary dysfunction after severe traumatic brain injury in children and adolescents: A large prospective study. J Clin Endocrinol Metabol 2014; 99: 2052-2060

Tanriverdi F et al. Three years prospective investigation of anterior pituitary function after traumatic brain injury. Clin Endocrinol 2008; 68:573-579

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