Intervention

timing of intervention Post ABI

To date, there are a lack of guidelines regarding when or how to treat endocrine dysfunction post ABI, including what medication to administer. It has been suggested that testing should begin immediately for those individuals who have been diagnosed with a moderate or severe ABI (Estes & Urban 2005), and are no longer in a coma or vegetative state. Those who sustain diffuse axonal injuries may be at even greater risk, regardless of injury severity, due to the rotational forces that the brain was subjected to (Estes & Urban 2005). It is reasonable to repeat screening at a minimum of 6 and 12 months post injury and again at 18 and 24 months in those who with severe injury or early DI.

Conditions that require immediate treatment are dysfunction of ACTH, ADH, and TSH. GHD has been shown to improve with time and may improve as other deficiencies improve. As well, GHD treatment in the acute phase is not recommended, as there appears to be no benefit (Sirois 2009). When there is clear indication of anterior or posterior pituitary dysfunction, consulting an endocrinologist is strongly recommended (Estes & Urban 2005). 

Immediate Hormone Replacement Therapy (HRT) 

Immediate hormone replacement therapy should be administered to patients with confirmed isolated or severe gonadal insufficiency. 

Gonadal Steroid Therapy

Androgen Replacement in Men or Testosterone Therapy

Treatments for hypogonadism in men include oral testosterone replacement therapy, subcutaneous implantation (3-6 pellets of 200mg unmodified testosterone every 4-6 months), intramuscular injections (testosterone esters), transdermal patches and gels, and buccal delivery (Nieschlag et al. 2004). Although several treatments are available and there are several evidence based guidelines on when and how to treat hypogonadism, there is no literature on the effectiveness of these treatments within the ABI population.

Estrogen Replacement in Women

Hormone replacement therapy in women has been shown to be effective during their menopausal or perimenopausal years. However, long-term treatment is not recommended due to the negative benefit-risk ratio (Auernhammer & Vlotides 2007). Other treatments for women may include the administration of dehydroepiandrosterone daily or testosterone. Although some success has been found using these treatments, neither has been studied within the ABI population.

Growth Hormone Replacement Therapy

In patients with a confirmed GHD, GH replacement therapy has been recommended, and it is often administered subcutaneously (Auernhammer & Vlotides 2007). The goal of therapy is to elevate serum IGF-I levels to at least the moderate range, which will vary depending on age and gender.

Table: GHD Intervention Post ABI

Discussion

Recent research has found that GH replacement therapy effectively elevates serum IGF-1 levels in individuals with GHD post ABI (Devesa et al. 2013), as well as improves their quality of life (Gardner et al. 2015; Moreau et al. 2013). In a RCT of individuals with TBI, patients received IGF-1 (5mg) via continuous intravenous infusion within 72 hours after injury and continued for 14 days, or placebo (Hatton et al. 1997). The authors found that patients receiving IGF-1 treatment showed better outcomes in terms of glucose concentration, nitrogen balance, body weight, and recovery (Hatton et al. 1997).

Conclusion

There is level 2 evidence that IGF-1 may improve clinical outcomes in patients with GHD post ABI.

There is level 4 evidence that GH replacement therapy may be effective in treating GHD post ABI by increasing IGF-1 levels. 

 

 

Growth hormone deficiency can be effectively treated with hormone replacement therapy and insulin growth like factor-1 therapy.

 

Interventions for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Treatments for hyponatremia resulting from SIADH include fluid restriction, hypertonic saline solution (Chen et al. 2014), enteral urea therapy (Annoni et al. 2016), and TRH stimulation (Zhang et al. 2010). However, the effectiveness of TRH stimulation is limited against hyponatremia resulting from Cerebral Salt-Wasting Syndrome. When higher doses of sodium supplementation are found to be ineffective, hydrocortisone may be considered as treatment (Moro et al. 2007). These interventions may be administered alone or with loop diuretics (Arai et al. 2009). Conivaptan is a medication that has been approved to treat hypervolemic hyponatremia, although it has yet to be studied within the ABI population. 

Table: Interventions for Syndrome of Innapropriate Antidiuretic Hormone (SIADH) Post ABI

Discussion

Retrospective studies have identified a number of successful treatments for SIADH including intravenous saline (Chen et al. 2014; Moro et al. 2007), restricting fluid intake (Chen et al. 2014), hydrocortisone (Moro et al. 2007), and enteral urea (Annoni et al. 2016). In one prospective study, Zhang et al. (2010) reported that TRH stimulation mitigated the symptoms of hyponatremia caused by ADH, but did not resolve hyponatremia caused by cerebral salt-wasting syndrome. Thus the effects of SIADH can be mediated by therapies that regulate levels of ADH and/or serum sodium.

Conclusion

There is level 4 evidence that saline solution, enteral urea therapy, TRH stimulation, and hydrocortisone may be effective in treating hyponatremia post ABI by reducing ADH levels.

 

 

Syndrome of inappropriate antidiuretic hormone can be effectively treated with a variety of interventions that regulate levels of ADH.

 

Interventions for Diabetes Insipidus

 Desmopressin has been shown to reduce urine output and liquid intake after head injury (Alaca et al. 2002; Born et al. 1985; Hannon et al. 2013)

Summary of Treatment

Table: Neuroendocrine Interventions Summary (Mitchell & Owens 1996)

Condition

Treatment

Dosage

Hypogonadism

Testosterone therapy (males)

 

 

Estrogen therapy (females)

Oral therapy

Subcutaneous implant

Intramuscular injection

Transdermal patches and gels

Short term treatment due to risks

ACTH Deficiency

Hydrocortisone

 

Prednisolone

20mg in morning and 10mg in early evening given orally, intramuscularly, or IV.

5-7.5mg/d given orally (1×/d).

TSH Deficiency

Synthetic TSH (Levothyroxine)

1mg orally before breakfast

GHD

Synthetic GH (Somatropin) or GHRH

0.06mg/kg is the maximum dose recommended and given subcutaneously or intramuscularly 3×/wk

SIADH

ADH inhibitor (Conivaptan)

20mg/d given by intraveous for short periods of time

DI

Desmopressin

0.1-0.4mL/d intranasally

 

Conclusion

The prevalence of neuroendocrine dysfunction varies considerably among studies and this may reflect the inaccuracy of testing methods. Neuroendocrine disorders often result in a variety of symptoms including temperature lability, appetite disturbances, decreased muscle mass, sleep disturbances, hair loss, decreased libido, and disorders of fluid regulation, or hypertension (Sirois 2009). With the exception of DI, other neuroendocrine disorders remain under reported and under diagnosed. Testing should be conducted while the patient is in acute care for ACTH and ADH deficiencies and then during the next 12 months for the remaining hormones. Failure to identify these dysfunctions could impact the individual’s recovery process and impact their overall quality of life.