A collection of resources and research on injuries to the pituitary.

Head Cases: Pituitary Incidents Arising from Traumatic Brain Injury

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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.”

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Concussions’ Lingering Effects Linked to Hormone Deficiency

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The finding may explain why even seemingly mild concussions can give rise to persistent maladies.

When a blast rattles the brain, the resulting concussion sometimes leads to unremitting psychological problems such as depression, anxiety, irritability, sleep disorders, pain, and learning and memory problems. Tens of thousands of American veterans are estimated to suffer from this postconcussive syndrome (PCS), formerly associated with shell shock. Now evidence suggests that a hormone imbalance may underlie the chronic symptoms—meaning hormone replacement therapy could spur a dramatic recovery.

At least since World War I, scientists have tried to figure out why about 10 percent of adults’ concussions—from any cause, including accidents, falls and sports injuries—lead to persistent psychological and physical complaints. Endocrinologist Charles Wilkinson of the VA Puget Sound and the University of Washington and his colleagues were intrigued by studies that found pituary hormone deficiencies, which affect only 1 percent of the general population, in many people who had had a concussion. No one had investigated whether a blast concussion could disrupt hormones as well, so Wilkinson’s team tested 35 soldiers who had been near a bomb explosion. They found that a whopping half of the soldiers had undergone a precipitous drop in growth and sex hormones compared with other deployed soldiers without any concussions. The data were presented in April at the Experimental Biology 2013 meeting in Boston.

The researchers hypothesize that the force of a blast physically disrupts the pituitary gland’s ability to either produce or transport its hormones. Receptors for growth hormone and its by-product hormone IGF-1 are found throughout the brain. The receptors’ locations—in areas such as the amygdala, prefrontal cortex, putamen and hippocampus—correspond with functions that are disturbed in PCS, including mood, sleep and memory. In addition, hormones are thought to affect plasticity, maintenance and protection of the brain. Wilkinson and his colleagues plan to test soon whether hormone replacement therapy could benefit patients with PCS—he is optimistic because such therapy has been shown to improve the same symptoms in people with hormone deficiencies from other causes. “There is considerable evidence that the cognitive and mood problems of growth hormone deficiency can be treated successfully with growth hormone replacement,” Wilkinson says.

Head Injury and Pituitary Dysfunction : Are we failing to Diagnose it?

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Recently a quarterback in the National Football League sustained a serious head injury. He was hospitalized for three days with a diagnosis of a serious concussion. The question needs to be asked, has any of his treating physicians considered the possibility of an injury to the pituitary gland? Did they draw a baseline IGF-1? Did they draw a Prolactin level or a cortisol level with an ACTH? Have they looked at FSH/LH level with testosterone? Does this sound like labs that are routinely done when an athlete presents with a head injury whether it is a major injury or even a minor injury? Unfortunately, these labs are not routinely done either in the emergency department, during the hospitalization or even after dismissal.

How will this failure to diagnose a possible pituitary problem affect this quarterback? For now, his injury will be contributed to the head injury itself and the doctors will anticipate that he will either get better or he won’t. If he does not return to his premorbid state, will he get the care that would return him to his previous level of functionality. We think not. Why, because too few doctors are educated about the problems of head injury and subsequent pituitary dysfunction or failure.

Fall is right around the corner and this means football games for all ages, from grade school up to professional players. Unfortunately with the fun comes injuries and some of those injuries can be very serious, even deadly. One of the injuries that may not appear to be obvious to coaches, trainers or even the doctors is an injury to the pituitary. Pituitary failure or dysfunction can occur with even mild trauma to the head.

Unless the medical team treating the injured player is suspicious of pituitary dysfunction, the injury will go undiagnosed only to cause problems for the player in the future. Rarely does the medical team include an endocrinologist. And even if the team did include an endocrinologist, few endocrinologists are educated about the relationship between head injury and pituitary failure or dysfunction. One of the major reasons the International Hormone Society was created, to educate doctors about the problems associated with head injury and pituitary injury and other frequently undiagnosed and untreated hormone related conditions.
Current research suggests that any injury to the pituitary that results in sustained hypoxia (hypovolemia) may result in pituitary damage. One of the first pituitary cells damaged are the somatotrophs (growth hormone secreting cells). The second pituitary cells, it is believed, to be damaged are the gonadotrophs (follicle stimulating and lutenizing hormone producing cells). It is unclear when the thyroid secreting hormone cells are damaged but it is known that the adrenocorticotropin cells (ACTH cells) are likely the last cells to be damaged.

It is known that 40% of the pituitary cells are somatotrophs, or growth hormone secreting cells. Many of these cells can be damaged and life will continue. The problem is that health will not continue. So, one of the first hormones that should be suspected to become deficient in a head injury is growth hormone. The screening test for growth hormone is the growth factor that is produced in the liver, insulin like growth factor one (IGF-1) as this is the form that persists in the body throughout the entire day.
Some studies of head injury suggest that prolactin may initially become elevated in head injury and then decline as the pituitary function declines. Prolactin would be a sensible baseline hormone to test in head injured patients.

It is logical that any insult to the head or the body would result in an elevated cortisol level (the stress response). The problem arises if the cortisol level is very high and is sustained for a prolonged period of time. In post traumatic stress disorder (PTSD), studies are revealing that a flood of cortisol may cause damage to cells in the hypothalamus, thus creating pituitary damage. A baseline cortisol level with and ACTH level would be helpful to predict whether the head injured patient may develop pituitary damage.

Thyroid stimulating hormone (TSH) is believed to be the main hormone that is be followed regarding thyroid disease. The problem with pituitary damage, the TSH may not elevate in the presence of thyroid disease or the TSH may not be produced and thus thyroid hormone is not released. It is imperative that a TSH, FREE T4 and FREE T3 be part of the labs drawn on the patient presenting with head injury.

If pituitary damage goes undiagnosed in a patient, the result will be impairment of quality of life and most likely a shortened life span. Quality of life is a difficult thing to measure but tools have now been developed to establish if a patient is suffering from impaired quality of life. One such tool measures specifically whether a patient has an impaired quality of life due to growth hormone deficiency. This tool is titled “Qualify of Life Assessment of Growth Hormone Deficient Adults”. This tool also should become part of the assessment of a patient suffering from a head injury.

A shortened life span can be the result of a pituitary deficient patient.