9.2 Pathophysiology of Hypopituitarism Post ABI

9.2.1 Vascular Blood Supply of the Pituitary Gland

Early investigations of the pituitary gland have shown that the majority of the gland’s blood supply comes from the long hypophyseal vessels 24The inferior hypophyseal artery supplies blood to the entire neurohypophysis and to a small section of the adenohypophysis 9;14.

Table 9.3 Vascular Supply of the Pituitary 14

Anterior Pituitary

a)  Superior hypophyseal artery

- Branch of internal carotid

b)  Capillary plexus formation with portal vessels

  - Primary and secondary

  - Run down in the stalk with 2 long portal vessels

c)  90 % of the anterior lobe is nourished by the portal system

Posterior Lobe

a)  Supply by inferior hypophyseal artery

b)  Short portal vessels

c)  1 capillary plexus

 

9.2.2 Mechanism of Injury

An anterior pituitary infarction may be caused by compression of the pituitary gland, the hypothalamus or interruption of the long hypophyseal vessels. This may be the result of direct trauma (skull fracture) or oedema, haemorrhage, raised intracranial pressure or hypoxic shock. Direct mechanical injury to the hypothalamus, the pituitary stalk or the pituitary gland may also result in hypopituitarism. An infarction of the posterior lobe can be avoided if the inferior hypophyseal blood vessels are not transected when the pituitary stalk is ruptured. Diabetes insipidus often occurs as the result of inflammation and edema around the posterior pituitary gland; however, this has been shown to improve with time 9.

 

9.2.3 Injuries Associated with TBI

Potential lesions associated with traumatic brain injury are shown in Table 9.4.  The types of injuries are listed below in Table 9.4.

 

Table 9.4 Potential Hypothalamic-Pituitary-Adrenal (HPA) lesions associated with Traumatic Brain Injury 14

Lesion

Causes of Injury

Location of Injury

 

 

Primary Lesion (direct)

 

Acceleration- deceleration

Traumatic lesion of the stalk

Anterior lobe necrosis

Posterior lobe haemorrhage

Basal skull fracture

Direct lesion to pituitary, stalk or hypothalamus

 

 

Secondary lesion (non direct)   

 

Brain oedema

Hypoxia

Increase intracranial pressure

Haemorrhage

Inflammatory mediators

 

Table 9.5 Types of Injury 23

Type of Injury

Percentage

Haemorrhage of hypothalamus

29%

Haemorrhage of posterior lobe

26%

Infarction of anterior lobe

25%

Infarction of posterior lobe

1%

Stalk resection

3%

In 7% of cases, neuroendocrine disorders are not associated with neuroimaging abnormalities. The gold standard for neuroendocrine dysfunction is serum testing tests assessing hormonal function 23.

9.2.4 Isolated & Combined Hormone Deficiencies 

Although early hormonal abnormalities are not necessarily associated with long-term PTHP 13, the most common problem following TBI is a single axis or hormonal insufficiency. 

What does the research tell us about chronic hormone deficits in those who have sustained an ABI.

Research has shown that chronic hormone deficits occur in 30 – 40% of patients following ABI with more than one deficiency occurring in 10 – 15% of the population2;5-7.

1.    Among individuals with an ABI growth hormone deficiencies may be seen in 20% of those injured; gonadal hormone deficiencies in another 15%-30%, prolactin elevation in 30% and hypothyroidism in 10%–30% of the population.

Chronic adrenal insufficiency and diabetes insipidus (DI) post ABI occurs much more commonly, especially in those with a severe TBI 10;12

 

Table 9.6  Isolated and Multiple Pituitary Axes Affected (%)

Post traumatic phase

1 axis (single deficiency)

2 or more (multiple deficiencies)

Acute

48%

28%

3 months

6.5%

6.5%

12 months

4.3%

6.5%

9.2.5  Clinical Presentation of Hypopituitarism

Neuroendocrine dysfunction may be seen as temperature lability, disturbances in appetite, weight fluctuations, hypothalamic and pituitary disorders, disorders of fluid regulation, hypertension or hypotension, fatigue, increased anxiety, depression, memory failure, cognitive deficiencies, reduced bone and muscle mass and immunologic disorders 8;14.

How does hypopituitarism present clinically?

1.    Fatigue,

2.    Sleep Disturbance,

3.    Decreased muscle mass, increased fat mass,

4.    Reduced exercise tolerance and muscle strength,

5.    Amenorrhea, decreased libido, erectile dysfunction,

6.    Decreased cognitive function, concentration, memory,

7.    Mood disturbances, depression, irritability,

8.    Social isolation, decreased quality of life.

 

Neuroendocrine disorders post TBI result from specific injuries to those areas that regulate physiological functions in various regions of the brain, specifically injuries along the hypothalamic-pituitary axis 18. Symptoms will vary depending on the area of the brain that has been affected by the injury.

Who does the current research suggest be tested for hormonal disorders or deficiencies?

1.    Current research suggests that anyone who suffers a brain injury (whether the result of a stroke or a traumatic brain injury) and has a GCS between 3 and 12 should be tested for hormonal disorders or deficiencies 9.

2.    Some discretion needs to take place in those patients with the most severe disability  (vegetative state) 8.

3.    Individuals at greatest risk for post-traumatic hypopituitarism (PTHP) are those who have sustained a diffuse axonal injury, a basal skull fracture, or who were older at the time of injury.

4.    Length of stay in ICU, longer hospitalization and a prolonged loss of consciousness may also play a role in the development of hypopituitarism 13.

In the acute phase, very early hormonal alterations may reflect adaptive responses to injury and critical illness and are not necessarily associated with long-term PTHP. Various studies have shown that the majority of patients with low grade or isolated deficiencies recover during the first 6 months post injury and tend to have a much better prognosis than those who do not recover 6;7;21. In one study, 5.5% of patients who showed no signs of PTHP deficiencies at 3 months did so later at 12 months. The same study showed that 13.3 % of patients who demonstrated isolated deficiencies at 3 months developed multiple deficiencies at 12 months 21. Growth hormone deficiency has been shown to be the most common deficit 7;21.

What are some of the complexities or issues in diagnosis hypopituitarism post ABI.

1.    Due to the nature of its features and the delay of its presentation, hypopituitarism may be missed following a stroke or an ABI 4.

2.    Some of the key indicators, such as low serum-like growth factor, may already be low in older patients due to normal aging.

3.    Studies looking at this issue to date indicate TBI severity, as measured by the GCS or EEGs, is not an accurate indicator of the likelihood of developing hypopituitarism.

4.    There is however, a trend to show an association with TBI severity 14.

9.2.6  Association with Severityof ABI

There is as of yet no clear association of the development of PTHP with the severity of TBI, the type of accident or the type of injury.  Although it has been shown by several researchers that PTHP patients had significantly lower GCS than unaffected survivors13;14;19; this has not been a consistent finding 19;21. The incidence of skull fractures and neurosurgical procedures has been reported to be similar in patients with hypopituitarism when compared to those with normal pituitary function 22.

Benvenga et al. 23have noted that hypopituitarism post TBI is primarily a disorder seen much more often with male survivors between the ages of 11 and 39 years. This is likely related to the fact that greater number of younger males tend to sustain head injuries more often. Currently there is no evidence that specific types of head injuries are more likely to lead to hypopituitarism 20. Due to the life threatening consequences associated with pituitary dysfunction, it represents a negative prognostic factor 23.