Veterans with mTBI Could Be Affected by Hormone Deficiencies

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Hypopituitarism May Cause Insomnia, Reduced Libido, Depression

By Annette M. Boyle

SEATTLE — For the 30% of warriors with concussive injuries whose symptoms fail to resolve in a few months, recent research offers new hope.

Researchers at the VA Puget Sound Health Care System and the University of Washington said they found that 42% of veterans with blast injuries suffer could suffer from hypopituitarism. Low levels of pituitary hormones might cause many of the most troubling lingering effects of mild traumatic brain injury (mTBI), including fatigue, insomnia, impaired cognition and memory loss, difficulty concentrating and emotional or mood disturbances.

Patients who report sexual or reproductive problems, depression or cognitive function issues six or more months after sustaining a concussion should be evaluated for hormone deficiencies, said Charles Wilkinson, MD, research physiologist, VA Puget Sound Health Care system, lead presenter of the results at the Experimental Biology 2013 meeting1 and lead author of a related study published in Frontiers in Neurology.2

As about 1 in 5 warriors deployed to Iraq and Afghanistan suffered at least one blast-related concussion, post-traumatic hypopituitarism (PTHP) might also explain difficulty treating other disorders. Some of the symptoms of hypopituitarism mimic post-traumatic stress disorder (PTSD), in particular, Wilkinson noted.

“That’s one of the most important aspects of the research,” he said. “While not all PTSD is due to PTHD, the two conditions have so many shared symptoms. If PTSD does not resolve, it’s very possibly due to hormonal deficiencies.”

Good News

A finding of PTHD could be good news for patients because, “PTHP is generally responsive to treatment with replacement hormones,” Wilkinson pointed out, adding that screening for hormone deficiencies “can potentially help a huge number of people” with any head injury. Following treatment to return hormone levels to normal, cognitive function improves, metabolic aspects such as lipidemia improve and mood issues often resolve.

For the study, researchers analyzed blood samples of 33 male veteran volunteers from the VA Puget Sound Health Care System. Twenty-six had experienced at least one blast in Iraq or Afghanistan and had been diagnosed with mTBI at least 12 months earlier.

As a control group, the researchers analyzed samples of seven men who had also served in Iraq or Afghanistan but did not experience a blast or have a history of TBI. The research team established normative hormone concentrations based on samples obtained from 59 age-matched cognitively normal male community volunteers.

All blood samples were screened for 12 pituitary and target-organ hormones: adrenocorticotropic hormone (ADTH), cortisol, follicle-stimulating hormone (FSH), growth hormone, insulin-like growth factor 1 (IGF-1), luteinizing hormone (LH), oxytocin, prolactin, testosterone, thyroxine, thyroid-stimulating hormone (TSH) and vasopressin.

Of the 26 mTBI patients, 11 had abnormal hormone values. Five of the 11 had IGF-I levels below the 10th percentile, while none of the control group did. Hypogonadism, as indicated by testosterone levels below the 5th percentile combined with luteinizing hormone or FSH below both 10th percentile, affected three of the participants with mTBI. Extreme vasopressin concentrations were identified in four participants and four had oxytocin levels below the 5th percentile.

These results are consistent with those seen in patients who have sustained mTBI from other causes, such as car accidents or sports injuries. Studies in the general population have found that 25% to 50% of individuals who experience TBIs also have pituitary hormone deficiencies. In both the VA and civilian research, growth hormone deficiencies and hypogonadism occurred most frequently.

Low levels of adult human growth hormone are associated with increased incidence of depression, irritability, aggressiveness, social isolation and sleep disorders, as well as cognitive impairment and detrimental effects on metabolism. Oxytocin and vasopressin deficiencies might affect personality and social behavior, potentially impairing key relationships. The deficiencies also be associated with mental disorders characterized by severe social disturbances, Wilkinson said.

He said the results were not surprising. “The stalk connecting the pituitary gland to the brain is very susceptible to compression. It is not well designed for blasts,” he noted. “It would be amazing if someone with a significant head injury from a blast or sports injury didn’t have some kind of brain damage. If that brain damage affects the pituitary gland, it may lead to hormonal abnormalities.”

The Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury recommend screening for neuroendocrine dysfunction (NED) in patients who have a history of mTBI and symptoms of NED that last for three months or longer or start within 36 months of brain injury. Symptoms of NED may include depression, emotional ability, anxiety, fatigue, poor memory, lack of concentration, loss of libido, infertility, amenorrhea, loss of muscle mass, increased body fat around the waist, weight gain or weight loss, low blood pressure, reduced heart rate, hair loss, anemia, constipation, cold intolerance and dry skin.

The Centers for Excellence recommend primary care physicians with patients with suspected NED screen for 0800 cortisol levels, LH, FSH, prolactin, IGF-1, TSH, FT4, and 0800 testosterone for males or estradiol for females.

Wilkinson said he wants to develop a standard screening approach for hypopituitarism that does not require provocative testing for growth hormone and adrenal hormones. Typically an insulin tolerance test would be used to assess hormone levels produced by the pituitary and adrenal glands, but it is contraindicated in head injuries, so a glucagon stimulation test is used instead. “The provocative tests are expensive, time consuming, require medical supervision and are very unpleasant for the patient,” Wilkinson said.

He said he hopes to use the Department of Defense’s serum repository to determine whether specific combinations of injuries are more likely to lead to hormonal abnormalities.

“If we can relate other aspects of combatants’ medical history to deficiencies, we can refine who needs to be screened. When combined with symptomology, screening could be very efficient,” Wilkinson added.

  1. Wilkinson CW, Colasurdo EA, Pagulayan KF, Shofer JB, Peskind ER. “Prevalence of Chronic Hyptopituitarism after Blast Concussion.” Program #935.3. Experimental Biology 2013 Meeting. April 2013.
  2. Wilkinson CW, Pagulayan KF, Petrie EC, Mayer CL, Colasurdo EA, Shofer JB, et al. “High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury.” Frontiers in Neurology. Feb 2012;3(11):2-12.

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