9.5 Treatment

What does the literature tell us about the appropriate time to begin treatment post ABI.

1.    To date there is no relevant data or guidelines on when to treat, how to treat or what medication to administer.

2.    It has been suggested that testing should begin immediately for those individuals who have been diagnosed with a moderate or severe ABI 16, and are no longer in a coma or vegetative state.

3.    Those who sustain diffuse axonal injuries (DAI) resulting from a MVA may be at even greater risk, regardless of the severity of injury, due to the rotational forces which the brain is subjected to 16.

4.    It is reasonable to repeat screening at a minimum 6 and 12 months post injury and again at 18 and 24 months post injury in those who had a severe injury or early diabetes insipidus.

What is the recommended for the treatment of ACTH?

1.    Hydrocortisone: 20 mg in morning and 10 mg early evening. The medication can be given orally, intramuscularly, or by IV.

2.    Prednisolone: 5 to 7.5 mg per day (to be given orally and 1 x a day).

Conditions that require immediate treatment are ACTH, ADH, TSH and panhypopituitarism. GHD as been shown to improve with time and may improve as other deficiencies improve; therefore, it is not necessary to begin treatments the moment it is diagnosed particularly if it is an isolated incidence. Also treatment in the acute phase is not recommended for GHD as there appears to be no benefit 14. For those who sustain a mTBI and a GH deficiency has been noted during regular blood work, but no other symptoms have appeared, it is suggested waiting 3 years post trauma to begin treatment to see if the condition will reverse itself. If possible, when there is clear indication of anterior or posterior pituitary dysfunction consulting an endocrinologist is strongly recommended 16.

9.5.1 Immediate Hormone Replacement Therapy (HRT

What medication has been recommended in the treatment of HRT?

1.    Somatropin 0.06 mg/kg subcutaneous or intramuscular (3x/wk) has been recommended as a treatment for HRT.

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

9.5.2 Gonadal Steroid Therapy

9.5.2.1 Androgen Replacement in Men or Testosterone Therapy

Although growth hormone deficiency (GHD) is not uncommon following an ABI, it is not as quickly diagnosed as other hormone deficiencies 2. Often GHD escapes detection for months or year post injury. Symptoms of growth hormone deficiency 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 15;18.

What is the recommended treatment for hypogonadism in males post ABI?

1.    Testosterone therapy is recommended for males who are diagnosed with hypogonadism post ABI. 

2.    Testosterone therapy can be administered in a variety of ways: implants, oral test therapy, intramuscular therapy, transdermal patches, intramuscular injection.

Treatments for hypogonadism include implants (implanting of 3 to 6 pellets of unmodified testosterone (200mg) subcutaneously every 4 to 6 months), oral testosterone replacement therapy, intramuscular injections (of testosterone esters), transdermal patches, transdermal gels, and buccal delivery 62. Although there are several treatments available and there are several evidence based guidelines on when and how to treat hypogonadism, there was no literature on how effective these treatments are within the ABI population.

9.6.2.2  Estrogen Replacement in Women

Hormone replacement therapy in women has been shown to be effective in women during their menopausal or perimenopausal years; however, long term treatment is not recommended due to the negative benefit-risk ratio 29. Treatment for women may include the administration of DHEA daily or testosterone and although some success has been found using these treatments, neither has been approved. 

9.6.3 Growth Hormone Replacement Therapy

What is recommended when there is a confirmed growth hormone deficiency?

1.    Synthetic GH (or GHRH) which is given by injection subcutaneously (either through a syringe or pen) is recommended. The maximum dose recommended is 0.06 mg/kg and is given subcutaneously or intramuscularly 3x/week.

In patients where there has been a confirmed growth hormone deficiency (GHD), the introduction of growth hormone replacement therapy has been recommended 29. The goal of therapy is to elevate serum IGF-I levels to the mid to high range. This range will vary depending on age and gender. Growth hormone is generally administered subcutaneously. Although this treatment has been tested with individuals who have not sustained a brain injury, there is no literature looking at this treatment within the ABI population.

9.5.4 Replacement Therapy for SIADH

What medication is given to treat SIADH?

1.    Conivaptan which is generally given intravenously (20 mg/day) is often given for shorts periods of time.

Treatments for hyponatremia include fluid restriction and administration of hypertonic saline solution. These treatments may be administered alone or with loop diuretics 63. Conivaptan, a new medication has been approved for use by the US-FDA to treat hypervolemic hyponatremia, but again it has yet to be studied within the ABI population.

9.5.5 Treatment of Diabetes Insipidus

What medication has been recommended to treat diabetes insipidus?
Desmopressin (DDAVP): 0.1 to 0.4 ml/day intranasally has been suggested to treat diabetes insipidus.

Diabetes insipidus has been found to be a leading cause of death in those who sustain a severe TBI 64. Desmopressin has been shown to reduce urine output and liquid intake 65.

9.5.6 Secondary Adrenal Insufficiency

What medication has been recommended to treat secondary adrenal insufficiency?

1.    Hydrocortisone: 20 mg in the morning and 10 mg early evening. Medication can be given orally, intramuscularly, or by IV

Moro and colleagues found that the administration of hydrocortisone was beneficial in reducing the amount of sodium excretion in a small group of patients with a TBI 38. Although the risk of adverse effects appears to be low, when administering hydrocortisone, more research is needed.

Conclusions

Neuroendocrine dysfunction post ABI is more frequent than initially thought. The prevalence varies considerably among studies and this may reflect the inaccuracy of actual testing methods. Neuroendocrine disorders often result in a variety of symptoms such as: temperature lability, appetite disturbances, decreased muscle mass, sleep disturbances, decreased hair, decreased libido, and disorders of fluid regulation, or hypertension 14. With the exception of diabetes inspidus other neuroendocrine disorders remain under reported and under diagnosed. Testing should be done while the patient is in acute care for ACTH and ADH deficiencies and then during the next 12 months for the remaining hormones. Although TSH is not a frequent deficit in the TBI patient GH, ACTH and LH/FSH are. Failure to diagnose these dysfunctions could impact the individual’s recovery process and impact their overall quality of life.