Physiological Disorders

Posterior Pituitary Dysfunction

Antidiuretic hormone dysfunction

Early studies investigating the impact of ABI on the posterior pituitary gland have demonstrated a disruption in sodium and fluid balance (Doczi et al. 1982). Makulski et al. (2008) noted that the more common medical consequences of acute TBI are disorders of salt and water balance resulting in inappropriate secretions of antidiuretic hormone (SIADH), hyponatremia, and DI. Abnormalities of ADH represent one of the most common endocrine disturbances that occur in patients following TBI (Powner et al. 2006).

syndrome of inappropriate secretion of antidiuretic hormone

SIADH has been diagnosed in patients when sodium serum levels drop below 135 mEq/L (hyponatremia) (Goh 2004), coupled with an inappropriate elevation of urine osmolality (Blumenfeld 2002). Given that adrenal insufficiency can be life-threatening, it should be evaluated when it is suspected in the acute phase (Sesmilo et al. 2007). It is generally accepted that adrenal, thyroid and gonadal function should be systematically studied 3-6 months after onset. Reassessment at 12 months should only be completed for those patients who had abnormal results at 3-6 months. Assessment for GHD should not be performed until other hormonal deficiencies have been managed (Sesmilo et al. 2007). It has been suggested that the use of medications such as carbamazepine, selective serotonin reuptake inhibitors (SSRIs), diuretics, vasopressin analogs, and chlorpromazine may lead to SIADH (Agha et al. 2005; Goh 2004; Haugen 2009). The following studies examine post-injury SIADH in more detail.

Table: Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) Post ABI

Discussion

Findings from three studies suggest that while SIADH post injury is not overly common, it has a greater incidence among patients with severe injuries than those with moderate or mild injuries (Born et al. 1985; Doczi et al. 1982). The onset of SIADH may present as early as 2 to 3 days post injury (Born et al. 1985), but it may also persist beyond 12 months (Moreau et al. 2012). Depending on the diagnostic criteria, SIADH is recognized as “severe” if serum sodium is <125-130 mmol/L (Born et al. 1985; Doczi et al. 1982). Severe syndromes may be associated with poorer neurological function compared to moderate syndromes, and may require daily fluid restriction to resolve symptoms (Born et al. 1985). There is not a widely accepted target range for fluid restriction. However, Doczi et al. (1982) suggested limiting daily fluid intake to less than 600-800mL, whereas Born et al. (1985) suggest limiting intake to 250-500mL.

Conclusions

There is level 5 evidence that individuals who sustain a severe ABI are more likely to develop SIADH than those with mild or moderate ABI.

There is level 5 evidence that restricting fluid intake may assist in the resolution of SIADH symptoms post ABI.

 

 

Individuals with severe ABI are more likely to develop SIADH.

Reducing the fluid intake of patients has been shown to be effective in treating SIADH post ABI.

 

Hyponatremia

Hyponatremia, defined as serum sodium concentration <136 mmol/L (Moro et al. 2007; Zhang et al. 2010), may result from SIADH or cerebral salt wasting (Moro et al. 2007). Symptoms of hyponatremia include lethargy, coma, or seizures. The following studies examine post-injury hyponatremia in more detail.

Table: Hyponatremia Post ABI

Discussion

Following injury, hyponatremia may result from SIADH or cerebral salt-wasting syndrome (Zhang et al. 2010). From three studies, the prevalence of hyponatremia post ABI ranged from 15% to 40% (Hannon et al. 2013; Moro et al. 2007; Zhang et al. 2010). Findings suggest hyponatremia is more common in patients with severe, as opposed to mild or moderate, ABI (Zhang et al. 2010). Hyponatremia is undesirable during recovery as it is associated with longer administration days and worse outcomes at 1 month from treatment (i.e., limited ‘good’ recovery, higher number of patients with moderate disability) (Moro et al. 2007).

Recommendations for the management of hyponatremia resulting from SIADH include limiting daily fluid intake and TRH stimulation (Zhang et al. 2010). The former, in particular, directly decreases the level of circulating ADH in blood, and thus may represent an effective therapy for SIADH-induced hyponatremia. Its effectiveness, however, is limited against hyponatremia resulting from Cerebral Salt-Wasting Syndrome (Zhang et al. 2010). Other ways to manage post-injury hyponatremia include IV or oral Na+ supplementation . Higher dosages of Na+ may be necessary if hyponatremia persists, and hydrocortisone should be considered if sodium supplementation is ineffective (Hannon et al. 2013; Moro et al. 2007). Moro et al (2007) reported that among patients with hyponatremia who did not respond to Na+ supplementation initially, hydrocortisone therapy was initiated, and their serum Na+ returned to normal range within 2 days of therapy.

Conclusions

There is level 4 evidence that thyroid releasing hormone may be effective in treating post ABI hyponatremia by reducing circulating antidiuretic hormone.

There is level 4 evidence that sodium supplementation therapy and hydrocortisone may be effective in treating post ABI hyponatremia.

 

Individuals with severe ABI are more likely to develop hyponatremia.

Thyroid releasing hormone therapy may be an effective treatment for hyponatremia post ABI.

Sodium supplementation therapy and hydrocortisone may be an effective treatment for hyponatremia post ABI.

 

Diabetes Insipidus

DI has been found to occur in patients with mild to severe TBI and can last from a few days to a month post injury (Tsagarakis et al. 2005). DI results in the production of large amounts of diluted urine. Post-injury DI may result from swelling around the hypothalamus or posterior pituitary but as the swelling begins to resolve itself so does the DI (Agha & Thompson 2005). Individuals suffering from DI may experience polyphagia, polyuria and polydipsia (Blumenfeld 2002).

Table: Diabetes Insipidus (DI) Post TBI

Discussion

In general, post-ABI DI is an uncommon condition. In a large observational study by Hadjizacharia et al. (2008), 15% patients with either blunt or penetrating head injury were diagnosed with DI. In studies with smaller samples, the rates ranged from approximately 2.0% (Bondanelli et al. 2007; Born et al. 1985; Ghigo et al. 2005) to 14% (Bondanelli et al. 2004), while a single study finding DI among 51% of participants (Hannon et al. 2013). DI appears to have a relatively early onset, occurring within a week of injury (Kelly et al. 2000), or even within a few days (Hadjizacharia et al. 2008). While most studies suggest that post-injury DI is transient (Bondanelli et al. 2004; Hannon et al. 2013; Kelly et al. 2000; Schneider et al. 2006; Schneider et al. 2008), there is some evidence that DI may persist up to 3 months and even 12 months post injury (Ghigo et al. 2005).

Multiple risk factors for DI post ABI have been identified (Hadjizacharia et al. 2008). Multivariable analysis showed that patients with severe injury, brain edema, head Abbreviated Injury Score greater than or equal to 3, and/or intraventricular hemorrhage were at a greater risk of developing DI following ABI. There are suggestions that extensive fractures at the base of the skull may also be an important risk factor for DI (Born et al. 1985). Presence of DI may also predict deficiencies in other pituitary axes, such as hypogonadism (Schneider et al. 2008). Further, DI has been reported as significantly associated with higher mortality in individuals with TBI (Hannon et al. 2013), as well as a leading cause of death in those who sustain a severe TBI (Maggiore et al. 2009).

Conclusions

There is level 4 evidence that extensive fractures at the base of the skull may serve as a risk factor for the development of diabetes insipidus post ABI.

There is level 5 evidence that severe injury, brain edema, and/or intraventricular hemorrhage may serve as risk factors for the development of diabetes insipidus post ABI.

 

Prevalence of diabetes insipidus post ABI ranges from approximately 2% to 51%.

Severe injury, brain edema, intraventricular hemorrhage, and extensive skull fractures may serve as risk factors for the development of diabetes insipidus post ABI.

 

Anterior Pituitary Dysfunction

Anterior Pituitary Dysfunction

Early research indicated that damage to the anterior pituitary was likely to be unreported post ABI (Yuan 1991); however, anterior pituitary dysfunction (APD) is now increasingly recognized (Sandel et al. 2007). APD may lead to a compromise in production of GH, TRH, PRL, glucocorticoid , and sex hormones (Sandel et al. 2007). Clinical presentation of APD varies widely, depending on the particular neuroendocrine axes affected, as well as the severity and rapidity of damage to that axis. The clinical presentation can range from subclinical disease to marked muscle or cardiovascular collapse (Sandel et al. 2007). 

The following studies monitored anterior pituitary function of individuals post ABI.

Table: Anterior Pituitary Dysfunction Post ABI

Discussion

Several studies have examined the prevalence of anterior pituitary deficiencies following ABI. The rate varies widely across studies, ranging from 15.4% to 76.4% (Bondanelli et al. 2007; Hannon et al. 2013; Klose et al. 2007; Kopczak et al. 2014; Moreau et al. 2012; Nemes et al. 2015; Prodam et al. 2013; Rosario et al. 2013; Ulfarsson et al. 2013). The onset of anterior pituitary deficiencies may occur within 24 hours of injury (Olivecrona et al. 2013; Tanriverdi et al. 2007) and may persist up to 12 months post injury, and in some cases longer (Agha et al. 2005; Agha et al. 2004; Bondanelli et al. 2007; Bondanelli et al. 2004; Ghigo et al. 2005; Kelly et al. 2000; Lieberman et al. 2001; Moreau et al. 2012; Nemes et al. 2015; Schneider et al. 2006).

Pituitary abnormality has been show to occur in one or more axes (Agha et al. 2004; Kelly et al. 2000; Klose et al. 2007; Kopczak et al. 2014; Lieberman et al. 2001; Schneider et al. 2006). However, there is no existing consensus as to which axis will be impacted or rendered impaired following an injury. For instance, impairments of GH was seen in 100% (n=10) of patients with isolated deficiency in one study (Klose et al. 2007), another study only reported it in 6% of patients (Lieberman et al. 2001).  As well, Lieberman et al. (2001) reported that injury severity was not related to the number of affected pituitary axes.

Risk factors for anterior pituitary deficiencies following injury have been identified in a number of studies. Cuesta et al. (2016) reported that men with hypogonadism and women with menstrual dysfunction had more deficiency of various pituitary hormones than those without such conditions. Greater injury severity was found to be associated with post-injury hypopituitarism (Bondanelli et al. 2004; Klose et al. 2007; Nemes et al. 2015; Prasanna et al. 2015). In contrast, Tanriverdi et al. (2007) and Agha et al. (2004) did not find differences in pituitary dysfunction by injury severity. In other studies, high body mass index was found to be a risk factor for pituitary dysfunction (Klose et al. 2007; Ulfarsson et al. 2013). Further, Schneider et al. (2008) suggested that greater diffuse axonal injury and basal skull fracture are associated with a higher risk of pituitary impairment.

Outcomes of patients developing anterior pituitary dysfunction may be negatively impacted, whereby their ability to make good recovery post injury may be significantly reduced (Kelly et al. 2000).  Marina et al. (2015) reported that Glasgow Outcome Scale (GOSE) and FIM at both 3 months and 1 year were associated with elevated stress hormones as well as suppressed thyroidal and gonadal hormones. Similarly, Prasanna et al. (2015) found that lower GOSE was associated with pituitary dysfunction, although Ulfarsson et al. (2013) did not find such results. As well, Rosario et al. (2013) reported that daily FIM gain was significantly lower in patients with hypopituitarism compared to those with normal function. However, the authors did not find any differences between those with and without endocrine function when comparing length of stay. Individuals with hypopituitarism have also been shown to have poorer Disability Rating Scores at discharge compared to those with normal function (Bondanelli et al. 2007). Prodam et al. (2013) found that individuals with hypopituitarism had higher prevalence of dyslipidemia and altered glucose metabolism.

In a systematic review (n=66), Lauzier et al. (2014) ported the prevalence, predictors, and clinical outcomes of anterior pituitary disorders following TBI. In the long term, 31.6% (n=27) of individuals were found to have at least one disorder. Predictors of these disorders were age (RR=3.19; n=19), injury severity (RR=2.15; n=7), and skull fractures (RR=1.73; n=6).  As well, anterior pituitary disorders were associated with increased ICU mortality (RR=1.79; n=4), but not Glasgow Outcome Scale score (n=3).

Conclusions

There is level 5 evidence that anterior pituitary dysfunction may present within 24 hours of injury and persist up to 12 months post ABI.

There is level 5 evidence that anterior pituitary dysfunction post ABI can occur in one or more axes in an unpredictable manner.

There is level 5 evidence that the development of anterior pituitary dysfunction may produce unfavourable outcomes post ABI including poorer recovery, greater length of stay, and higher level of disability.

 

The incidence of anterior pituitary dysfunction post ABI ranges from 15% to 76%.

Anterior pituitary dysfunction may present within 24 hours of injury and persist up to 12 months post ABI.

Anterior pituitary dysfunction post ABI can occur in one or more axes in an unpredictable manner.

Several risk factors have been reported to be associated with the development of anterior pituitary dysfunction post ABI; however further research is required.

Compared to individuals with normal function, the development of anterior pituitary dysfunction may produce unfavourable outcomes post ABI including poorer recovery, greater lengths of stay, and higher levels of disability.

 

Growth Hormone Deficiency

Although GHD is not uncommon following ABI, it is not as quickly diagnosed as other hormone deficiencies (Lieberman et al. 2001). GHD often escapes detection for months or years post injury. The signs and symptoms of GHD include fatigue, decreased muscle mass, osteoporosis, exercise intolerance, dyslipidemia and truncal obesity as well as a number of cognitive deficits and a poorer quality of life (Table below)(Sandel et al. 2007; Schneider et al. 2007).

Table: Clinical Presentation of Growth Hormone Deficiency

  • Headaches, sleep disturbances, energy loss, fatigue, insomnia
  • Attention/concentration disorders, decrease cognitive performance
  • Irritability, depression
  • Low self–esteem, poor quality of life
  • Muscle wasting, decrease lean body mass, weight gain (visceral obesity)
  • Decrease VO2 max, decrease exercise tolerance, fatigability
  • Atherosclerosis, osteoporosis, dyslipidemia

 

The following studies examine post-injury GHD in more detail.

Table: Growth Hormone Deficiency Post ABI

Discussion  

There has been consistency across studies regarding methodologies employed to assess GHD. For example, GST or Insulin Tolerance Test (ITT) was commonly performed to elicit a GH response, which was compared directly against values obtained from healthy matched individuals receiving the same stimulation test. When ITT was contraindicated in patients due to seizure or heart condition, GHRH+arginine test served as a replacement. When stimulation tests were not used, GHD was identified by deferring to basal IGF-1 values.

The prevalence of post-injury GHD varied considerably across studies, ranging from 2.8% to 63.6% (Agha et al. 2005; Agha et al. 2004; Bondanelli et al. 2007; Bondanelli et al. 2004; Ghigo et al. 2005; Kelly et al. 2000; Kleindienst et al. 2009; Klose et al. 2007; Kopczak et al. 2014; Lieberman et al. 2001; Moreau et al. 2012; Schneider et al. 2006; Tanriverdi et al. 2007). As well, persistent deficiencies up to and beyond 12 months were commonly noted (Agha et al. 2005; Agha et al. 2004; Bondanelli et al. 2004; Ghigo et al. 2005; Kelly et al. 2000; Kleindienst et al. 2009; Lieberman et al. 2001; Schneider et al. 2006; Tanriverdi et al. 2013).

Multiple findings suggest that higher BMI is associated with higher incidence of post-injury GHD (Agha et al. 2004; Lieberman et al. 2001; Schneider et al. 2006; Tanriverdi et al. 2013). Other predictors of GHD include low IGF-1 levels (Agha et al. 2005; Agha et al. 2004; Bondanelli et al. 2007; Lieberman et al. 2001; Olivecrona et al. 2013; Schneider et al. 2006; Tanriverdi et al. 2013), older age (Bondanelli et al. 2004; Schneider et al. 2006), and more severe injury (Kleindienst et al. 2009; Tanriverdi et al. 2013). Conversely, other studies did not find that GHD was associated with BMI (Agha et al. 2005; Aimaretti et al. 2005; Bondanelli et al. 2004) or injury severity (Agha et al. 2005; Bondanelli et al. 2004).

Outcomes associated with GHD are not well documented, but findings suggest that cognitive functions (Bondanelli et al. 2007; Moreau et al. 2012), performance on FIM (Bondanelli et al. 2007; Rosario et al. 2013), level of disability (Bondanelli et al. 2004; Kreber et al. 2016), and level of independence (Kreber et al. 2016) may be negatively impacted by the presence of GHD. Olivecrona et al. (2013) reported no significant relationship between GH or IGF-1 levels and GCS or GOS, while Tanriverdi et al. (2007) found no significance difference in GH levels or survival by injury severity.

Conclusions

There is level 5 evidence that the development of growth hormone deficiency may produce unfavourable outcomes post ABI including poorer cognitive functioning, lower Functional Independence Measure scores, and higher Disability Rating Scale scores.

 

 

Prevalence of growth hormone deficiency post ABI ranges considerably from 2.8% to 63.6%.

Several risk factors have been reported to be associated with the development of post-ABI growth hormone deficiency; however further research is required.

Compared to individuals with normal functioning, the development of growth hormone deficiency may produce unfavourable outcomes post ABI including poorer cognitive functioning, lower levels of functional independence, and higher levels of disability.

 

Gonadotropine Deficiency/LH-FSH Deficiency

Hypogonadism is often one of the earliest symptoms of hypopituitarism in those who survive a TBI (Lee et al. 1994). In males, it is important to monitor testosterone concentrations as low levels in the absence of elevated LH levels may indicate hypogonadism. In premenopausal women monitoring estradiol levels is important, as low levels of estradiol in the absence of elevated FSH may be a sign of hypogonadism. Testosterone deficiencies in males and estradiol deficiencies in women may also be a sign of hypogonadism. In both genders hypogonadism has been associated with sexual dysfunction, reduced vigour, mood disorders, insomnia, loss of facial, pubic and body hair, osteoporosis and infertility (Hohl et al. 2009; Schneider, Aimaretti et al. 2007). 

Table: Clinical Presentation of Gonadotropic Deficiency

  • Testosterone and estrogen/progesterone deficiency
  • Hypogonadism: oligomenorrhea, amenorrhea, infertility, sexual dysfunction, decreased libido
  • Muscle atrophy, osteoporosis, hair loss
  • Reduced tolerance to exercise
  • Decreased memory and cognitive performance

 

There is no consensus as to when to test for hypogonadism post injury. Due to uncertainty around the time when neuroendocrine disorders appear and disappear post injury, Hohl et al. (2009) suggested testing patients with TBI at least one year after injury for hypogonadism. Agha and Thompson (2005) suggested testing 3 to 6 months post injury, with follow-up testing at 12 months. The following studies examine post-injury GD in more detail.

Table: Gonadotropic Dysfunction Post ABI

Discussion

Gonadotropic deficiency (GD) is common among individuals with ABI, whereby acute prevalence rates range from 13% to 80% (Agha & Thompson 2005; Aimaretti et al. 2005; Barton et al. 2016; Hohl et al. 2014; Kleindienst et al. 2009; Kopczak et al. 2014; Lee et al. 1994; Olivecrona et al. 2013; Rosario et al. 2013; Schneider et al. 2006; Tanriverdi et al. 2007). Persistent deficiencies up to and beyond 12 months have been commonly reported (Agha et al. 2004; Agha & Thompson 2005; Aimaretti et al. 2005; Bondanelli et al. 2007; Bondanelli et al. 2004; Kelly et al. 2000; Kleindienst et al. 2009; Klose et al. 2007; Lieberman et al. 2001; Moreau et al. 2012; Schneider et al. 2006)

Common predictors of post-injury GD include older age (Agha et al. 2004), transient DI, polytrauma, hypoxia (Schneider et al. 2008), and severe injury (Cernak et al. 1999; Kleindienst et al. 2009). Several studies found that GD was associated with poor GCS scores (Agha & Thompson 2005; Cernak et al. 1999; Kleindienst et al. 2009; Schneider et al. 2006), although other studies have not reported this relationship (Bondanelli et al. 2007; Tanriverdi et al. 2007). Compared to individuals with normal hormone functioning, GD was also found to be associated with poorer scores for the Functional Independence Measure, Disability Rating Scale, cognitive function (Barton et al. 2016; Bondanelli et al. 2007), and Glasgow Outcome Scale scores (Agha & Thompson 2005; Barton et al. 2016). GD was also correlated with lower FIM gains per day (Rosario et al. 2013) and less clinical improvement on the modified Rankin Scale (Schneider et al. 2006). However, one study reported that the rate of GD did not differ between individuals who survived and did not survive (Tanriverdi et al. 2007).

Conclusions

There is level 5 evidence that gonadotropic deficiency post ABI is associated with lower Glasgow Coma Scale scores. 

 

Prevalence of gonadotropic deficiency post ABI ranges from 13% to 80% and can persist up to 12 months, and in some cases longer.

Gonadotropic deficiency post ABI is associated with greater injury severity.

Compared to individuals with normal functioning, the development of gonadotropic deficiency may produce unfavourable outcomes post ABI including poorer cognitive functioning, lower levels of functional independence, and higher levels of disability.

 

Hyper/Hypoprolactinemia

Hyperprolactinemia has been shown to be present in more than half of patients with ABI in the early acute phase and it is believed that approximately 30% of patients show symptoms (Bondanelli et al. 2005). Kilimann et al. (2007) found males had higher levels of PRL than females and more males were found to have hyperprolactinemia than females. However, it should be noted that all patients with hyperprolactinemia also had an infection, were hypoglycemic, or were on medications known to increase PRL levels (dopamine antagonists, GABA agonists, opiates or central catecholamine depletors). The following studies examine post-injury PRL dysfunction in more detail.

Table: Prolactin Dysfunction Post ABI

Discussion

The rate of post-ABI hyperprolactinemia widely varies across studies, ranging from 5% to 50% (Agha et al. 2005; Aimaretti et al. 2005; Bondanelli et al. 2004; Kleindienst et al. 2009; Klose et al. 2007; Kopczak et al. 2014; Lieberman et al. 2001; Moreau et al. 2012; Olivecrona et al. 2013; Schneider et al. 2006; Tanriverdi et al. 2007). It is important to note, however, that the rate of post-injury hyperprolactinemia may be lower if patients receiving hyperprolactinemia-inducing drugs are excluded from the analysis (Kopczak et al. 2014; Lieberman et al. 2001; Schneider et al. 2006). Based on a limited number of studies, the rate of post-ABI hypoprolactinemia ranged from <1% to 8% (Bondanelli et al. 2004).

Post-injury hyperprolactinemia may persist up to 12 months post injury (Agha et al. 2005; Ghigo et al. 2005; Kleindienst et al. 2009; Schneider et al. 2006). However, it is difficult to predict whether individuals sustaining ABI will develop hyperprolactinemia. Agha et al. (2005; 2004) reported that post-injury hyperprolactinemia was not associated with factors such as age, sex, or GCS score; although a later study reported that GCS scores were negatively correlated to post-injury PRL levels (Tanriverdi et al. 2007). Given the apparent lack of association with negative outcomes, hyperprolactinemia may not be a significant deterrent to patient recovery (Olivecrona et al. 2013).

Conclusion

There is level 5 evidence that hyperprolactinemia may not be associated with injury severity or recovery outcome post ABI.

 

Prevalence of hyperprolactinemia post ABI ranges considerably from 5% to 50%; however prevalence rates may be impacted by hyperprolactinemia-inducing drugs.

 

Adrenocorticotropic Hormone Deficiency (ACTH)

ACTH secretion tends to fluctuate at night and increase with stress, physical activity and chronic disease. Cortisol levels taken in the morning are low and there is a poor cortisol response to ACTH stimulation (Sandel et al. 2007). The signs and symptoms of ACTH deficiency are listed in the table below (Schneider et al. 2007). 

Table: Clinical Presentation of Adrenocorticotropic Hormone Deficiency

  • Fatigue, weakness, anorexia, nausea, vomiting
  • Hair loss
  • Low blood pressure
  • Hypoglycemia
  • Absence of hyperpigmentation
  • Poor quality of life
  • If acute, may be life-threatening

 

The following studies examine post-injury ACTH and cortisol deficiency (CD) in more detail. 

Table: Adrenocorticotropic Hormone Deficiency

Discussion

Findings from multiple studies suggest that ACTH (or cortisol) deficiency within 1 week of injury can vary considerably in rate, ranging from 8.8% to 78% (Hannon et al. 2013; Olivecrona et al. 2013). It is suggested that injury severity is an important predictor of ACTH deficiency, whereby more severe injuries are associated with more frequent or more profound ACTH deficiencies (Kleindienst et al. 2009; Tanriverdi et al. 2013; Tanriverdi et al. 2007). Other factors may include older age, injury to the basal skull, and lack of cranial vault fracture (Schneider et al. 2008). It is important to note, however, that there are inconsistencies as to whether these factors do in fact play a role in inciting post-injury corticotropic complications (Agha et al. 2005; Agha et al. 2004; Bondanelli et al. 2007; Olivecrona et al. 2013), and thus some caution is necessary when interpreting the findings.

Individuals living with ABI may continue to demonstrate post-injury ACTH deficiency for up to 12 months (Ghigo et al. 2005) and beyond (Kleindienst et al. 2009; Tanriverdi et al. 2013). This may be problematic for recovery, as post-injury ACTH deficiency has been shown to be associated with poorer cognitive and physical outcomes (Moreau et al. 2012), as well as with other anterior pituitary disturbances such as hyperprolactinemia, low testosterone, and low tT3 and fT4 (Kleindienst et al. 2009), and higher mortality (Hannon et al. 2013). Further, there is a lack of known treatment options available to manage post-injury ACTH deficiencies.

Conclusion

There is level 5 evidence that adrenocorticotropic hormone deficiency may produce unfavourable outcomes post ABI including mortality.

 

Prevalence of adrenocorticotropic hormone deficiency post ABI is variable ranging from 8.8% to 78% and persisting up to 12 months and beyond.

Several risk factors have been reported to be associated with the development of post-ABI adrenocorticotropic dysfunction; however further research is required.

Compared to individuals with normal functioning, the development of adrenocorticotropic hormone deficiency may produce unfavourable outcomes post ABI.

 

Thyroid-Stimulating Hormone Deficiency

TSH deficiency appears to be less common than other hormonal deficiencies post ABI (Schneider et al. 2007). Reduced thyroid function may lead to a decrease in an individual’s basal metabolic rate and cognitive function, and an increase in fatigue (Elovic 2003). In children, TSH deficiencies may lead to growth retardation (Alexopoulou et al. 2004). The signs and symptoms of TSH deficiency are listed in the table below, many of which do not present until much later in the recovery period (Schneider et al. 2007). 

Table: Clinical Presentation of Thyroid-Stimulating Hormone Deficiency  

  • Constipation
  • Fatigue, paleness, cold intolerance
  • Muscle atrophy, muscle cramps, weight gain, myopathy
  • Coarse voice, macroglossia
  • Bradycardia, hypotension, anemia
  • Anemia
  • Pre-orbital edema
  • Neuropsychiatric disorders (hallucinations, delirium)

 

Diagnosing TSH deficiency has been shown to be more difficult, as the symptoms are often masked by other hormonal deficiencies post ABI. The treatment of TSH deficiency is often with levothyroxine (Yamada & Mori 2008). The following studies examine post-injury TSH deficiency in more detail.

Table: Thyroid-Stimulating Hormone Deficiency

Discussion

Multiple studies found that post-ABI TSH deficiency is uncommon, with very few individuals displaying symptoms at or greater than 6 months post injury (Agha et al. 2005; Agha et al. 2004; Bondanelli et al. 2007; Kelly et al. 2000; Klose et al. 2007). Impaired thyrotropic function is undesirable from a recovery standpoint, as a trend toward poor cognitive outcome was observed in individuals with thyrotropic dysfunctions (Moreau et al. 2012; Zetterling et al. 2013).

Findings by Kleindienst et al. (2009) suggest that more severe injuries are associated with greater incidence of low TSH and fT4 levels, and thus post-injury thyrotropic complications. Earlier findings by Cernak et al. (1999) demonstrated that individuals with severe TBI had more profound thyrotropic disturbances than those with mild TBI. More specifically, those with severe TBI had decreased TSH levels for the entire duration of the study (7 days), whereas those with mild TBI showed an elevated TSH response for only a few days post injury. These findings are inconsistent with Tanriverdi et al. (2007), who reported that no significant differences in mean TSH levels were found among individuals with mild, moderate, and severe injuries. The discrepancy across studies indicates that there is still considerable uncertainty regarding predicting outcomes for those with post-injury thyrotropic complications (Moreau et al. 2012).

Conclusion

There is level 5 evidence that thyroid-stimulating hormone deficiency is associated with greater injury severity.

 

Thyrotropic deficiency is uncommon post ABI.

Post-ABI thyrotrophic deficiency may be associated with injury severity.