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In age of internet diagnoses, endocrinologists confront myth of ‘adrenal fatigue’
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Recent data from the CDC reveal that reports of chronic stress and fatigue are on the rise in the U.S. According to the 2016 National Health Interview Survey, 3.5% of respondents reported serious psychological distress vs. 2.7% in 2007, whereas 13% reported feeling restless some of the time. National Health Interview Survey data from 2011 revealed that 15% of women and 10% of men reported feeling very tired or exhausted.
The data come at a time when more patients are turning to the internet seeking answers to address such symptoms, and misinformation is rampant in a rapidly expanding mass media landscape. According to a 2013 Pew Research Center study, 72% of Americans search for health information online, with about 35% searching for diagnostic information. For those researching nonspecific symptoms like fatigue, an inability to handle stress, mild depression or a lack of energy, a common term will surface in online searches — “adrenal fatigue.”
The term, first coined by James Wilson, DC, ND, PhD, in 1998, is described as a collection of signs and symptoms that result when the adrenal glands are not functioning as they should. Yet the symptoms said to be associated with so-called adrenal fatigue — an inability to focus, feeling tired all the time, lack of enthusiasm or energy — are often “pain of life” symptoms that many people have, according to Alice C. Levine, MD, professor of medicine, endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai.
“A common complaint is, ‘I just don’t feel like I used to feel,’” Levine told Endocrine Today. “People land on this idea that they have just gotten so stressed out that their adrenal glands have become exhausted and are no longer providing them with cortisol. There is no substantiation of this in the literature. In fact, studies done on patients with chronic fatigue syndrome show no dysregulation in their adrenal-pituitary axis.”
A lack of empirical evidence supporting such a condition has not tempered interest in adrenal fatigue as a diagnosis. Numerous online outlets, typically featuring advice from naturopaths, promote the idea, and mainstream media outlets, including NBC’s Today show, have given attention to the “debate” around whether adrenal fatigue is real.
The result is more patients heading to an endocrinologist’s office requesting treatment for a disease that experts maintain does not exist.
“Charlatans scam patients with the concept of adrenal fatigue, which shows a complete lack of understanding of human physiology to even come up with that term,” Richard Auchus, MD, PhD, professor of pharmacology and internal medicine in the division of metabolism, endocrinology and diabetes at the University of Michigan, told Endocrine Today. “These are not endocrinologists giving this ‘diagnosis.’ They do not follow guidelines, and they made up this disease, and they are harming patients with this concept.”
The trend is particularly frustrating in the setting of the current endocrinologist shortage, Auchus said, as clinicians are spending more time with patients convinced they have a faux disease or, worse, needing treatment after taking supplements that created a new health condition. The Endocrine Society states that adrenal fatigue is not a real medical condition and published a patient-friendly fact sheet on its Hormone Health Network website.
“We spend a lot of our time dealing with people who don’t have an endocrine problem, and that’s another problem in endocrinology,” Auchus said. “There are so many people who need our time and effort, and we don’t have time for them because charlatans have invented this disease that, unfortunately, bears the names of our organs. The Endocrine Society and AACE have done a good job of trying to debunk these myths and hold the line, but some people distrust the medical profession.”
Battling a belief
True primary adrenal insufficiency, or Addison’s disease, is rare, affecting approximately 110 to 144 of every 1 million people in developed countries, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Secondary adrenal insufficiency — adrenal hypofunction due to a lack of adrenocorticotropic hormone (ACTH) — is more common and typically treated with oral glucocorticoid therapy.
But the many vague symptoms attributed to so-called adrenal fatigue are almost by nature designed to apply to most people, according to Theodore C. Friedman, MD, PhD, chairman of the department of internal medicine and endowed professor of cardiometabolic medicine at Charles R. Drew University of Medicine and Science in Los Angeles. The goal, Friedman said, is usually to push sales of dubious supplements and tests not typically used by endocrinologists, such as saliva testing of cortisol levels.
Wilson’s website, which usually appears at the top of internet searches for “adrenal fatigue,” notes that conventional medicine does not recognize adrenal fatigue as a “distinct syndrome.”
“You may look and act relatively normal with adrenal fatigue and may not have any obvious signs of physical illness, yet you live with a general sense of unwellness, tiredness or ‘gray’ feelings,” the website states. “People experiencing adrenal fatigue often have to use coffee, colas and other stimulants to get going in the morning and to prop themselves up during the day.”
The site goes on to promote saliva testing of cortisol, noting that “unfortunately, many physicians are still unaware of the validity, reliability and value of saliva hormone tests.”
“The way the adrenals work is they are a fast-forward regulation system,” Friedman told Endocrine Today. “When you’re under stress, the adrenals make more cortisol, not less. It doesn’t make any sense to have low cortisol in the setting of high stress. In rare cases — someone who was in a war, for example — under that kind of extreme stress, adrenals can stop working. But not the everyday person, say, taking care of a sick parent. This belief could lead to misdiagnosis. A person could have other things wrong with them.”
In a study published in BMC Endocrine Disorders, Flavio A. Cadegiani, MD, PhD, of the adrenal and hypertension unit at Federal University of Sao Paulo, and colleagues performed a systematic review of 58 studies conducted through April 2016 that assessed cortisol profile and fatigue or energy status as the primary outcome (33 studies with healthy adults and 25 with symptomatic patients). The most assessed exams in the studies were direct awakening cortisol (n = 29), cortisol awakening response (n = 27) and salivary cortisol rhythm (n = 26).
The researchers observed conflicting findings from most study methods employed, regardless of the validation and quality of the performed tests. The researchers cited poor-quality assessments of fatigue, the use of cortisol assessments not endorsed by endocrinologists and inappropriate conclusions regarding causality and association, among other concerns.
“Although conflicting data were reported, patients with [chronic fatigue syndrome] tend to have a normal cortisol profile, and the abnormalities found can typically be explained by poor quality sleeping patterns,” Cadegiani and colleagues wrote. “Therefore, health providers should not be concerned about adrenal function in [chronic fatigue syndrome] subjects once they had been already excluded to other conditions prior to the diagnosis of [chronic fatigue syndrome].”
The key, according to experts, is convincing patients that they need to consider something else.
“With the advent of the internet, social media moves concepts around very quickly,” Lynnette K. Nieman, MD, senior investigator with the NIH NIDDK and 2018 president of the Endocrine Society, told Endocrine Today. “There are a lot of endocrine disorders where people do come in saying they know they must have gained weight because they are hypothyroid, or they must have gained weight because they have a glandular problem. Endocrinology affects so many parts of the body, that in some ways it does seem mystical to patients. Once you have something like adrenal fatigue that is appealing to people, it is going to catch on.”
Evaluation of symptoms
In patients with true adrenal insufficiency, Auchus said, symptoms will be clear on presentation.
“Severe disease is easy to diagnose and has an amazing response to treatment,” Auchus said. “If you see somebody with adrenal insufficiency, newly diagnosed, they are very sick. They’re losing weight, they’re throwing up, ... their ACTH is in the hundreds or thousands, their cortisol is undetectable and their electrolytes are off. And then, when you give them that first dose of hydrocortisone, they’re a new person.
“If you have symptoms that are severe, and your lab tests are normal, it is not due to that organ,” Auchus said. “It’s common sense.”
For patients with more nonspecific complaints, Nieman said, other health issues could be at play.
“When you start thinking about someone with fatigue, they could have anemia, they could have an infection, they could have heart failure,” Nieman said. “Many things can cause fatigue, and that is oftentimes the main thing people come in with. Or, they have concerns about getting through the day. Many times, those people seem somewhat depressed. Whether that is the only thing wrong with them is unclear.”
Emotional stress, depression and anxiety should always be a default diagnosis that occurs only after all other medical causes have been exhausted, Levine said, who stressed the importance of a general endocrine history and workup.
“My initial workup would be to check all the hormonal axes,” Levine said. “I check cortisol and ACTH. In a woman not on a birth control pill or males, I would check sex steroids, prolactin, TSH and free T4, and their [complete blood count] to look for anemia. If they complained of weight gain or, in a female, hirsutism and acne, then I would be checking androgen levels as well.”
In women of reproductive age, the clinician should get a menstrual history, Levine said.
“Hormones talk to each other,” Levine said. “Regular periods are usually the first thing to go. In young women of reproductive age, you can get a progesterone level to see if they ovulated.”
Clinicians should also take careful note of any medications a patient is taking.
“A physical and history is important, particularly medicines and things people don’t consider medicines,” Levine said. “The two biggest offenders in the field of any kind of adrenal illness are narcotics, because they affect the pituitary adrenal axis, and anything that looks like a glucocorticoid.”
Steroids, such as prednisone, but much more commonly, long-acting injectable steroids for pain, are a common cause behind what appears to be secondary adrenal insufficiency upon testing, Levine said. Even cortisone creams and scalp injections for conditions like alopecia, or inhaled corticosteroids for conditions like asthma, suppress endogenous cortisol over time, Levine said.
“I will often get a consult where they tell me I have such an interesting case — they look like they have Cushing’s disease, but their cortisol level is really low,” Levine said. “And I’ll think to myself, you know, it’s really not that interesting. When you get that combination, it means there is a smoking gun somewhere.”
Supplement dangers
According to the 2016 National Health Statistics Report on trends in the use of complementary health approaches, 34% of adults used any complementary health approach in 2012, with the most popular being nonvitamin, nonmineral dietary supplements. Data showed a 60% increase in the 30-day prevalence of using fish oil — said to reduce BP and increase brain blood flow — as well as an increase in the 30-day use of melatonin, prebiotics and probiotics.
Patients should be especially cautious when shopping for supplements to “treat” so-called adrenal fatigue, Nieman said. Typical supplements recommended on popular naturopath sites include Indian ginseng, licorice and holy basil leaf, whereas some outlets promote adrenal glandular, or ground-up adrenal glands.
“Sometimes, these supplements do have substances like cortisol,” Nieman said. “You can cause other problems by having too much. That is one risk of supplements that have glucocorticoids in them. “
Auchus recalled treating several patients who experienced the effects of taking glucocorticoid supplements, sometimes for years.
“It’s a life-threatening situation when people have been given pharmacologic doses of glucocorticoid inappropriately that they now need to withdrawal from,” Auchus said. “Because if they get sick during this time, they could die without emergency hydrocortisone injections, just like anyone with Addison’s disease. They’ve taken a problem and made it worse, and people have developed avascular necrosis of the femoral neck from being on glucocorticoid therapy for ‘adrenal fatigue.’ That is permanent; they’re not going to get those hips back. This is serious harm.”
Licorice supplements, too, can act as a mineralocorticoid and raise BP in some patients, Nieman said, whereas other agents, like St. John’s wort, can interact with medicines patients are taking, making them more or less effective.
Some supplements can have an “adrenaline-type effect,” Friedman said, and should be discussed with patients.
“Herbs may be harmful if an extract of adrenal glands is present,” Jonathan Leffert, MD, FACP, FACE, ECNU, president of AACE, told Endocrine Today. “They are expensive and distract from evaluation and treatment of the real underlying problem.”
Role of the endocrinologist
When the endocrinologist has a patient claiming to have adrenal fatigue, it is important to go back to the beginning, Leffert said.
“Our job as physicians is to figure out the patient’s problem and determine if there is anything from an endocrinologic perspective that we can do for them,” Leffert said. “Sometimes we have to be good physicians and internists, which endocrinologists are all trained as, and start from scratch. All these patients are suffering from something, it’s just that the adrenal fatigue diagnosis doesn’t explain it, because it doesn’t exist.”
Levine said it is crucial that an endocrinologist establish trust with a patient coming in with a complaint to create an opportunity to find answers.
“I never dismiss the complaint,” Levine said. “The complaint is real. What I try to do is create a relationship with the patient. I tell them that I am going to give a hormonal tuneup, and make sure that, under my watch, it isn’t something in the endocrine system, in the adrenal system. But, I need you to partner with me because I want to wind up with you feeling better, and not just have a diagnosis. Partner with me by stopping anything I ask you to stop, and trust that I am going to follow every possible lead here. But, at the end of the day, if I do not find an endocrine cause for those symptoms, I think it is in your best interest that you move on.”
“The most important thing is that you explain to the patient that you’re trying to help them,” Auchus said. “That’s why I say that I start with the history and the physical, I evaluate them, and then we get in our discussion. I can say I have already examined you and listened to your story, and this is what I think. Recognize and assure the patient that you know they are not feeling well and they want to get better, and that you want them to get better. But this is not what they have, and you have to point them in the right direction.” – by Regina Schaffer
- References:
- Cadegiani FA, et al. BMC Endocr Disord. 2016;doi:10.1186/s12902-016-0128-4.
- CDC. MMWR Morb Mortal Wkly Rep. 2013;62(14):275.
- CDC. National Health Interview Survey 2016. Available at: ftp.cdc.gov/pub/Health_Statistics/NCHS/NHIS/SHS/2016_SHS_Table_A-8.pdf. Accessed Feb. 22, 2018.
- Hormone Health Network. Adrenal Fatigue. Available at: www.hormone.org/diseases-and-conditions/adrenal/adrenal-fatigue. Accessed Feb. 22, 2018.
- Nahin RL, et al. Natl Health Stat Report. 2016;95:1-11.
- NIH. Adrenal Insufficiency and Addison’s Disease. Available at: www.niddk.nih.gov/health- information/endocrine-diseases/adrenal- insufficiency-addisons-disease. Accessed Feb. 22, 2018.
- Pew Research Center. Health Online 2013. Available at: www.pewinternet.org/2013/01/15/health-online-2013/. Accessed March 13, 2018.
- For more information:
- Richard Auchus, MD, PHD, can be reached at the Endocrine Oncology Clinic, 1500 E. Medical Center Drive, University of Michigan Comprehensive Cancer Center, Level B1, Reception E, Ann Arbor, MI 48109; email: rauchus@med.umich.edu.
- Theodore C. Friedman, MD, PhD, can be reached at Charles R. Drew University of Medicine & Science, 1731 E. 120th St., Los Angeles, CA 90059; email: theodorefriedman@cdrewu.edu.
- Jonathan Leffert, MD, FACP, FACE, ECNU, can be reached at North Texas Endocrine Center, 9301 North Center Expressway, Suite 570, Dallas, TX 75231; email: jleffert@leffertmail.com.
- Alice C. Levine, MD, can be reached at Mount Sinai School of Medicine, Division of Endocrinology, 1 Gustave L. Levy Place, New York, NY 10029; email: alice.levine@mountsinai.org.
- Lynnette K. Nieman, MD, can be reached at the NIH Intramural Research Program, Section on Reproductive Endocrinology, 10 Center Drive, Building 10, Room 1-3140, Bethesda, MD 20892; email: niemanl@nih.gov.
- Disclosures: Auchus reports he has served as a consultant for Diurnal. Leffert is president of AACE. Nieman is president of the Endocrine Society. Friedman and Levine report no relevant financial disclosures.
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