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Recommending cortisol measurements in all patients with fatigue, in the absence of other signs or symptoms of true cortisol deficiency, cannot be well-justified.
Fatigue is a very common complaint by patients, either in an endocrinologist’s office or in primary care offices. Unfortunately, the imaginary concept of “adrenal fatigue” has been promoted by integrative medicine and naturopaths for many years now. The concept that chronic stress, whether it be physical or psychological, can somehow down-regulate pituitary adrenal function is not supported by any clinical science. In fact, the contrary is true.
I see at least one patient per month who has visited a naturopath and undergone cortisol measurements or taken a cortisol test purchased from a website. In either case, patients typically provide saliva samples taken in the morning, afternoon, early evening and at bedtime. Naturopaths then put together a cortisol profile, constructing a reference range for the patient that is so narrow that no normal person could ever have all four samples within the “normal” range. Even if the cortisol levels were above or below the average range, patients are told they have adrenal fatigue, usually at different “stages.” It’s ludicrous.
There are a few exceptions in which a cortisol measurement might be useful. Patients on opioid therapy, for example, often have low cortisol, and about 10% to 15% of them will develop adrenal insufficiency, depending on how you define that. Many of these patients do complain of fatigue, and whether or not treating those patients provides benefit is not clear. Although the evidence for this is not terribly good yet, when extra stress is imposed on these patients who have low cortisol levels from opioids, we think they have a normal response. But, this is a very challenging group of patients, particularly since the majority of opioid-treated men have a low testosterone level.
Fatigue is usually not the only complaint in true adrenal hypofunction. Often, it is accompanied by things like weight loss, vomiting, diarrhea and other, more objective metabolic derangements like electrolyte abnormalities or low sodium levels. In my practice, when patients complain of fatigue, my next question is always, “Do you snore?” The most underappreciated cause of fatigue in patients I see in my practice is sleep apnea.
If fatigue is the only complaint, or it is not accompanied by things like weight loss, electrolyte abnormalities or some imaging abnormalities in the pituitary gland, screening people for cortisol deficiency is difficult to justify.
James W. Findling, MD, FACP, is professor of medicine and director of the Community Endocrine Center and Clinics at the Medical College of Wisconsin. Disclosure: Findling reports no relevant financial disclosures.
Measuring cortisol is not a bad idea, but it has its own issues and limitations.
Fatigue is a common problem, and the causes of fatigue, which can range from simple lack of sleep, to anemia, sleep apnea or other issues, are too many to address just in a few minutes. Nevertheless, a low cortisol level appears to be one possible cause. However, I don’t jump the gun and test cortisol levels right away. I conduct a thorough patient history to elicit symptoms and pick up causes for fatigue. Very often, fatigue can be seen in people who have too much cortisol as well as those who have less than normal amounts of the hormone. Importantly, other hormonal problems, such as thyroid or pituitary problems, could lead to fatigue.
What is unique about the fatigue associated with cortisol levels? People who have low cortisol often speak of a pattern: They have relatively decent or somewhat better energy level in the morning, and then as the day goes on, they tend to have lower amounts of energy. The common description patients often mention is, “I run out of gas by mid or late afternoon.” Depending on the cause or the concern or the adrenal problem, patients with low cortisoloften have associated symptomatology. It is our job, as physicians, to try to elicit these symptoms. One of them, particularly in women before menopause, is the loss of hair in the pubic area and the axilla and a decrease in libido, even though they may still be menstruating. This is a very common feature in people who have adrenal problems. One of the characteristic features in adrenal diseases is, before people lose the function of the glucocorticoids, specifically cortisol, their body loses androgen first. In women with a low cortisol, nine out of 10, if not all of them, would have already lost their adrenal androgen before that. By exam or by history, one can elicit this very easily.
We also must look at family history, specifically, problems with autoimmune process.
Many things can interfere with cortisol measurements, particularly any medications a person is taking, such as an inhaled glucocorticoid, injected or cream steroids. A common example that is often overlooked is the use of an oral contraceptive, which could give you a falsely elevated cortisol level. Chronic opioid use is a consistent cause of adrenal dysfunction or insufficiency. The important thing is if you were to measure the cortisol level, please appreciate its limitations and interpret the value with caution.
For a long time, I have also advocated for measuring the main adrenal androgen, dehydroepiandrosterone, when one suspects an adrenal problem. The test is exquisitely sensitive to adrenal dysfunction. Anytime that test is normal, you can safely say there is no adrenal insufficiency. That said, I would not perform that test alone but in conjunction with cortisol testing, knowing that measurement of cortisol has its own limitations.
Baha M. Arafah, MD, is division chief of clinical and molecular endocrinology and professor of medicine at Case Western Reserve University. Disclosure: Arafah reports no relevant financial disclosures.