Head Cases: Pituitary Incidents Arising from Traumatic Brain Injury

With over 2 million Americans suffering from traumatic brain injuries each year, these incidents can often lead to pituitary dysfunction. 

Recent headlines of disabling head injuries to returning Iraq and Afghanistan war veterans as well as recurring concussions to professional athletes have placed the incidence of traumatic brain injuries (TBI) front and center in mainstream medical news. TBIs, however, have long been a leading cause of death and disability in the U.S., and what happens to the body’s hormone system following these injuries has become an increasingly significant public health concern.

Each year in the U.S., about 2.5 million children and adults suffer a TBI caused by either a blow to the head, penetrating head injury, or repeated jolts to the head, according to the Centers for Disease Control and Prevention (CDC). And more than 5.3 million Americans are currently living with a lifelong disability due to TBI.

Injuries that disrupt the normal function of the brain can range from mild to severe. And, although, not usually referred to as such, concussions are TBIs. “A concussion is a mild, traumatic brain injury. It’s just a euphemism,” points out neurologist Brent E. Masel, MD, national medical director for the Brain Injury Association of America, Vienna, Va.

The most common causes of TBI depend on the age group. For children between the ages of birth and four years and seniors 65 years and older, falls cause the most hospitalizations, reports the CDC. Young adults ages 15–24 have the highest TBI hospitalizations due to motor vehicle traffic–related events. Violence (e.g., child abuse, gunshot wounds, or beatings) and injuries from sports or combat round out other common causes.

The Brain and Hormones Changes

Trauma to the brain may interfere with the normal production and regulation of the hormonal processes of the hypothalamus and pituitary glands. Th e hypothalamus and pituitary are the most vulnerable and often most affected by brain injury. Depending on the injury, problems that can occur right away include adrenal insufficiency, diabetes insipidus, and hyponatremia. Other problems may not surface until months or years later, and the most common are growth and gonadotropin hormone deficiencies leading to symptoms such as growth problems, fatigue, weight gain, low blood pressure, low libido, loss of muscle mass, and amenorrhea.

Many studies have shown that a high percentage of patients who suffer mild, moderate, or severe TBIs may have some form of pituitary dysfunction in the first three months following the injury. While most of these patients’ symptoms go away over the following nine months or so, many still have pituitary hormone dysfunction by the end of a year.

In a literature review in the February issue of Endocrine, author Alan Rogol, MD, PhD, from the division of pediatric endocrinology at the University of Virginia in Charlottesville, reported the prevalence of pituitary dysfunction following TBIs among both children and adults ranges widely from 5% to 90%. A major reason for the studies’ variation in ranges was the time interval between the injury and the screening for pituitary function, the review suggested.

“Head injuries are very common in children, and it is the vast minority that lead to endocrine dysfunction,” Rogol says. In one of the larger studies cited of 1,000 TBI patients, there was a prevalence of some form of hypopituitarism in 27.5%.

At Johns Hopkins University, neuroendocrinologist Gary Wand, MD, treats about four patients a year who experience pituitary dysfunction due to TBI, including professional athletes and war veterans. He stresses that when there are endocrine deficits, the most important of the impaired endocrine system is the pituitary’s control over the adrenal axis, the stress hormone system, and the production of cortisol. “Th e adrenal axis is the one that can be life threatening early on in a traumatic brain injury because you can get hypotensive, so that system has to be assessed and the patient has to be supported in terms of replacement with stress hormones,” he says.

“It turns out that the two systems that are most vulnerable to injury are the production of growth hormone and the production of sex hormones,” Wand says, adding that growth hormone is not only a hormone for children to reach adult height; adults require growth hormone to maintain lean body mass, bone mass, bone strength, and bone density.

When to Screen, When to Treat?

There is no debate that TBI-related endocrine dysfunction is a widely missed diagnosis. Th e healthcare providers who are first to treat these injuries are often unaware of potential long-term effects.

“Emergency room staff [and primary care doctors] are the ones seeing the kids come in with the head injuries and they’re thinking concussion and all the old school stuff about concussion-causing headaches, maybe some dizziness, and vomiting,” says Wand. “They’re thinking the kids are going to get better, and they’re just not aware that you can have these hormonal changes.”

Diagnosing post-TBI dysfunction involves serum screening tests including: 0800 cortisol levels, thyroid stimulating hormone, luteinizing hormone, follicle stimulating hormone, IGF, free thyroxine, testosterone for male patients, and estradiol for females. However, there have been several published guidelines on the recommended screening intervals and even treatment.

Rogol says there are a lot of transient deficiencies in the first year that make it difficult to base lifelong treatment on early results. “The best screening is a careful history of symptoms of adrenal, thyroid, or gonadotropin defi ciency or much more importantly, the quantitation of linear growth,” he says.

In the February issue of the Journal of Endocrinological Investigations, researchers in Spain concluded that “invasive and expensive” endocrine assessments may not be warranted for children with mild to moderate TBIs.

Th e team evaluated 36 children with TBI (mean age seven), who all had skull fracture or intracranial hemorrhage. Nearly 37% had moderate to severe TBI, and the average time between the study assessment and injury was three years. No evidence of pituitary dysfunction was observed in these patients after clinical follow-up, repeated baseline hormone levels, or dynamic function tests.

“Based on our results, we consider it might not be justifi ed to perform dynamic tests in children with mild to moderate TBI unless baseline hormonal levels are low or clinical findings suggest endocrine dysfunction,” says author Itxaso Rica of the Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders. “Blood tests may represent a stressful event for children and their families. Also, they have to be taken at 8:00 a.m., which can make it more difficult for families,” she adds. “Furthermore, stimulation tests are not free from risks and further costs.”

When it comes to more serious brain injuries, differing opinions also raise questions on what is, indeed, the appropriate treatment course, says Masel. “Th e problem is that the endocrinologist will say you don’t treat growth hormone deficiency until a year after a moderate to severe brain injury,” he says. “There were some guidelines that were published and the feeling was that endocrinologists should wait until you’re sure the deficit is stable because although you test a patient say three weeks after their brain injury, everything may be normal. But a fair percentage become abnormal by month 12.”

“My personal feeling, is as soon as I’m medically stable [out of the ICU], screen me, and we’ll go from there, but endocrinologists, I have learned, are very conservative,” Masel adds.

Wand cautions that there are two sides to the coin. “Remember, because the hormonal changes in many people were reversed, you certainly don’t want to commit people to lifelong hormone replacement therapy until you know for sure they’re not going to recover,” he says. “At the same time, you don’t want to make the mistake of leaving somebody without hormone replacement if they’re not going to recover. So you know there’s good judgment that needs to be taken into account for these cases.”

In Rogol’s Endocrine review, the authors concluded that growth hormone therapy showed some improvement across published literature, but recommended it only if the patient is “objectively deficient in GH.”

Masel acknowledges the difficulty endocrinologists face and says more research is needed to foster more definitive treatment protocols. “As a physician, it’s a pain in the butt,” he says. “You have to screen them, and then you have to do a definitive test, and then you have to recommend a medication, and then you have to fight with an insurance company.”

“Growth hormone is somewhere between $15,000 and $18,000 a year for an adult, and it’s that way in an overwhelming number of people the rest of their lives, so insurance companies aren’t keen about the diagnosis, so they put up roadblocks. I understand all that.”

— A regular contributor to Endocrine News, Fauntleroy is a freelance journalist based
in Carmel, Ind. She wrote about food as medicine in the June issue.

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