Hormone Dysfunction After Concussion: An Interview with Dr. Tamara Wexler
Tamara L. Wexler, MD, PhD
Clinical Associate Professor, Department of Rehabilitation Medicine, NYU School of Medicine
Director, Neuroendocrine Associates: https://neuroendocrineassociates.com/ and 804-270-5484
Dr. Tamara Wexler is an endocrinologist who specializes in neuroendocrinology and reproductive endocrinology. She is a Clinical Associate Professor at the NYU Langone Medical Center where she specializes in the treatment and study of hormone dysfunction following traumatic brain injury.
The following interview for Concussion Alliance was conducted by Maya Strike, an intern in our December 2020 Concussion Education & Advocacy Internship Program, and Julian Szieff, who is a member of the Concussion Alliance Leadership Team. Some edits were made for clarity.
Julian Szieff: For a patient who has been struggling for a while, when and for what kind of patient or kind of symptoms should they consider getting a hormone screening?
Dr. Tamara Wexler: People who have had concussions have a higher rate of pituitary hormone deficiencies than the general population. People with mild injuries can develop chronic pituitary deficiencies and people with severe injuries can develop chronic pituitary deficiencies.
Since many people have suffered from concussions, there is a lot of interest in determining whom to screen. I find symptoms to be the best indicator. Patients themselves may notice these symptoms or providers may recognize signs and symptoms. Symptoms that might be due to endocrine dysfunction (though can also stem from something else) include cognitive slowing or “brain fog,” unexplained changes in weight, temperature regulation changes, menstrual cycle irregularity, sexual dysfunction, changes in mood, and/or changes in energy, arising or continuing beyond three months after the injury.
As far as determining whom to screen for pituitary dysfunction, I would say it really comes down to the provider's clinical judgment. If a patient continues to suffer from persistent symptoms at least 3 months after a concussion, or if someone a year out from a concussion is still not feeling like him or herself, I think it's worth considering whether pituitary dysfunction might be a contributing factor. While not everyone with fatigue or difficulty concentrating will have a pituitary dysfunction, when there is a hormonal deficiency, replacing the hormones should help reverse related symptoms.
Maya Strike: What does the process of getting a hormone test look like for patients? Which providers can order these tests and what will be involved in getting the test?
Dr. Tamara Wexler: The best first person to address potential endocrine dysfunction is somebody who has been overseeing the patient’s care, whether that be a primary care physician or a neurologist or a physical medicine and rehabilitation doctor. While awareness that hormones can be altered after concussion is increasing, it’s still not very high, so it might take saying, "A higher risk of hormone deficiencies has been described after concussion, and I'm interested in pursuing that." The provider or the patient may be the one to raise the question. Or, the patient could see a neuroendocrinologist or endocrinologist who specializes in pituitary hormones.
Any provider can order the relevant lab tests, but it's important to know how to interpret and follow up on the test results. Waiting a month or two months to see a physician who can help with a pituitary evaluation is not dangerous, with the exception of a deficiency in stress hormone. (If initial testing suggests that someone might be deficient in cortisol-- stress hormone-- it is important to follow up on that quite quickly, as problems that are not addressed can be more dangerous in the short term.)
Julian Szieff: Can you talk about the different pituitary hormones that we could expect to see dysfunction in, and then are there any differences in those based on the age of a patient or the sex of a patient?
Dr. Tamara Wexler: The pituitary acts like the thermostat for your house, the master regulator of different hormonal systems. It makes sure that everything's in balance.
The first hormonal system, or axis, to evaluate is the cortisol axis. Cortisol is also called “stress hormone,” and it does go up when people are emotionally stressed or physically stressed, but it's also essential for supporting blood pressure in times of stress. This is the one axis in which a deficiency (called “adrenal insufficiency”) can be dangerous in the near term: individuals with adrenal insufficiency who are physically stressed may not be able to maintain their blood pressure.
The thyroid axis is evaluated by measuring both the stimulating hormone that comes from the pituitary gland, “thyroid stimulating hormone” (“TSH”), and the active thyroid hormone. It is necessary, when evaluating pituitary hormone systems, to look at all pieces of the puzzle at once.
Evaluation of the sex hormone axis differs depending on gender. In males, an evaluation for deficiency includes testosterone as well as the pituitary hormones “luteinizing hormone” (“LH”) and “follicle-stimulating hormone” (“FSH”). Testosterone should be measured in the morning when it is usually the highest. In women, estradiol is measured along with the same pituitary hormones (LH and FSH). A prolactin level should be measured in men and women. Prolactin is a hormone that is usually suppressed by signals to the pituitary from the hypothalamus, and any interruption to the hypothalamic-pituitary axis can release that inhibition, with a subsequent elevation in prolactin. A high prolactin can suppress the FSH and LH, and may offer a possible reason for low testosterone or estradiol.
The last axis to be measured is the growth hormone axis. Growth hormone is the most common chronic pituitary deficiency reported after concussions. Normal ranges of growth hormone vary based not just on sex but on age.
For hormones in general, expected normal levels may differ in children, adolescents, and adults at different ages. For example, as people age, testosterone levels and growth hormone levels decrease. Using the appropriate age-matched range of “normal” is important. When testing hormone levels, all lab results should include reference ranges that are age- and sex-matched. Also, hormone levels vary throughout the day. In looking for a deficiency, it is important to measure the hormone at the time of day when it is the highest, to ensure that a low measurement doesn’t just represent a natural low point. (Thus, in looking for adrenal insufficiency or testosterone deficiency, cortisol and testosterone levels should be measured in the morning.)
Maya Strike: What will treatment and management of hormonal dysfunction entail for patients?
Dr. Tamara Wexler: Once a deficiency is diagnosed, the deficient hormone can be replaced. If someone has more than one deficiency, it is important to replace them in a specific order. Cortisol must be addressed first because it may be dangerous if deficient and not replaced—for example, if someone with untreated adrenal insufficiency takes thyroid hormone, it can precipitate what's called an “adrenal crisis.” The stress hormone axis has to be stably replaced for a few months, before the thyroid hormone axis is addressed. Once the thyroid axis is addressed (or if it is functioning normally to begin with), then the sex hormone axis can be addressed. Once deficient sex hormones are replaced –again, for a few months--then growth hormone can be addressed.
The medications themselves come in various forms. For replacement, thyroid medicine and cortisol are pills; testosterone may be an injection, patch, or gel; estrogen is usually a pill, patch, or cream; growth hormone is an injection.
Julian Szieff: How often are hormone levels checked to see if they are being appropriately replaced?
Dr. Tamara Wexler: It can take time to get to the right level. Too little is bad and too much is bad, and you do not want to be over-replaced. When someone first begins replacement, there will probably be more frequent measurements, as often as every one to two months. Once someone is on a stable dose, unless there is a change in symptoms, levels may be monitored only once or twice a year.
Even if a patient has normal hormone results when first evaluated, if symptoms persist or new symptoms develop, a repeat evaluation should be considered. You can develop deficiencies later on as a result of a concussion. It's also true that you can recover from deficiencies after a concussion, so it's important to consider reevaluation in patients on replacement hormones—if their own systems recover, they won’t need to stay on the replacement.
Maya Strike: Is it common that you see symptoms either resolving on their own or resolving then returning or fluctuating or is it usually a pretty predictable pattern?
Dr. Tamara Wexler: For the patients I see, it's not that predictable, but many patients do feel better over time. It’s common for a patient to feel better in some ways, but not entirely back to normal. Fluctuating symptoms are also pretty common. Additional issues or injuries may also affect both health and evaluation. For example, if somebody gets COVID, that will have its own impact and its own process of getting better and can muddy the picture.
Julian Szieff: What do you hope will be researched and developed in the next five or ten years to help guide this field? Do you see any key developments coming along the way or things that you want to research?
Dr. Tamara Wexler: I think it is important to develop a set of multidisciplinary evidence-based guidelines for providers, and hope this is imminent.
Further research is important as well. In terms of research, there's not a lot of clinical controversy over what constitutes a deficient hormone, but that's not reflected in all published research. Growth hormone in particular is measured in different ways in the literature, and, on top of that, the threshold used to define deficiency varies between papers. The population being studied also makes a difference: if a study only looks at people who are in a rehab setting, the results really only apply to others in a similar setting.
It’s important to be very careful with how one designs a study so that it's really measuring what one wants to look at. I think it's important to consider not only whether there are deficiencies, but the effects of the replacement. Let’s say an individual is going through other types of cognitive or physical rehabilitation--it would be useful to know how hormone replacement affects their overall rehabilitation. I would expect that they may impact one another. Overall, considering carefully exactly what you want to answer, and taking a very rigorous approach, are important. There are good papers out there, we just need more.
Maya Strike: Can you talk about your work in telemedicine and specifically why you feel it's necessary to have that option for patients?
Dr. Tamara Wexler: I didn't plan to start seeing patients in telemedicine. It was solely because of the pandemic. I’d certainly prefer to see someone in person when possible. However, since much of neuroendocrinology is based on patient history (and laboratory testing), you can do a lot via telemedicine.
I do think that telemedicine also provides a good way to see people in follow-up. In the future, I imagine that patients might establish a relationship in person with a care provider, and have in-person physical exams, but may choose to have follow-up appointments virtually. The pandemic has really forced a shift in the way we think about how to provide quality, accessible medical care.
Currently I only “see” patients in states where I have a medical license, either a full license or a pandemic-specific limited license. While individual state licenses are usually needed to see patients in that state, I wonder if the pandemic will lead to a longer-term change in how medicine may be practiced.