“Dear Doctor,

Controversy has been noted recently about cortisol testing to assess adrenal function. Several endocrinologists have raised questions about the clinical use of salivary Cortisol testing, because the standard-of-care has been the use of blood and urine tests.

Blood (and urine) tests for cortisol are used to help diagnose Cushing’s syndrome and Addison’s disease, two serious adrenal disorders. Physicians are now using salivary Cortisol measurements to diagnose Cushing’s syndrome, as well as to evaluate possible stress-related disorders. Both the urine and saliva tests are most frequently used to evaluate cortisol production. Once an abnormal cortisol concentration has been detected, the doctor will do additional testing to help confirm the excess or deficiency and to help determine its cause.

Dexamethasone Suppression to assess Cortisol excess

If there is excess cortisol production, the doctor may perform a suppression test to help determine whether the cause of the cortisol is related to excess ACTH production by the pituitary. This test involves giving the patient oral dexamethasone (a synthetic glucocorticoid) and then measuring their blood and urine cortisol levels. Dexamethasone suppresses ACTH production and should decrease cortisol production if the source of the excess is pituitary related. However, the Journal of Clinical Endocrinology & Metabolism states that salivary testing is as accurate as plasma measurements and better than urine glucocorticoid excretion to detect Cushings syndrome.

ACTH Stimulation to assess Cortisol deficiency

If there is concern about insufficient cortisol production, the doctor may order an ACTH stimulation test. This test involves measuring the concentration of cortisol in a patient’s blood before and after an injection of synthetic ACTH. If the adrenal glands are functioning sufficiently, then cortisol levels will rise with the ACTH stimulation. If they are damaged, then the response will be limited. This ACTH stimulation test is useful to determine if the patient may have Addisons disease. However, the vast majority of patients who have a decline in the diurnal variation and total amount of salivary Cortisol do not have Addisons Disease.

Research in the area of psycho-neuro-endocrinology has defined alterations in normal adrenal Cortisol response curves as a function of various physical, psychological, and emotional stressors. This altered biologic response of the adrenal glands has been called Adrenal Fatigue. Adrenal Fatigue is a mild form of adrenal insufficiency affecting the rhythm of the adrenal glands, rather than their ability to function normally when stimulated.

With Adrenal Fatigue, the ACTH Stimulation test will usually result in a normal reading because the issue with the syndrome is not whether the adrenals can be stimulated to produce cortisol but whether they can maintain the level of cortisol in a steady rhythm as needed by the body. Adrenal Fatigue is also referred to as a condition of low adrenal reserve, meaning the adrenals can at times function at normal or sub-normal levels but cannot complete full daily cycles of supplying cortisol to the body as it is needed. This leaves the persons body in a stressed-out state at the end of a day of coping with stressors.

Stress and Adrenal Fatigue

Stress researchers have used salivary Cortisol as an effective measure of quantifying the physiologic effect of stress on the body. Hans Selye, who defined the term stress in 1946, noted changes in the adrenal glands that were seen with physical and emotional stressors. More that half of the 2500 papers published on salivary Cortisol are specifically on the topic of stress. Thus, researchers in the area of psycho-neuro-endocrinology refer to the response to chronic stress as a syndrome of stressed adrenals. The symptoms of diminished stress-coping include fatigue, nervousness, depression, irritability, the need for stimulants and a low tolerance for stressors of any kind. The syndrome often manifests in people who have experienced traumatic events (Post Traumatic Stress Disorder) or chronic stress, meaning unrelenting, prolonged and severe. It often also manifests in people with chronic diseases, including thyroid conditions, diabetes, cancer and autoimmune diseases of all types. Adrenal Fatigue has been cited in many medical research studies, as playing a major role in conditions such as Chronic Fatigue Syndrome, Fibromyalgia and Post traumatic Stress Disorder. While the condition is not referred to as Adrenal Fatigue in these research studies, it is fully described as a condition of mild adrenal insufficiency and as hypocortisolemia, among other terms.

Salivary Cortisol Tests are Accurate

Medical groups that have studied adrenal-cortisol testing by saliva samples, have determined this type testing to be accurate, as well as less intrusive and more convenient than blood sampling. In these studies, multiple levels can be obtained at different points of a full day-cycle (24 hour period) which is difficult to accomplish by blood sampling. Saliva samples can be done in the convenience of a persons home while multiple blood draws would require long stays or repeated visits to blood draw clinics when taking multiple samples during a 24-hour period. In addition, salivary testing is the method of choice for field studies or ambulatory assessments in the natural environment of the subjects because medical personnel or laboratory facilities are not required for collecting and storing the samples.

A Value of Blood, Urine and Salivary Cortisol Testing

As has been shown, there is value in different types of Cortisol testing to evaluate different functions (and dysfunctions) within the adrenal glands. Classically blood testing is used and can help to define severe diseases, such as Cushings Syndrome and Addisons Disease. It should be noted that these blood tests measure the total amount of hormone, both bound and unbound, which can mis-represent the biologically active, free (unbound) portion of Cortisol circulating in the blood. Studies demonstrate that the salivary Cortisol changes in parallel with the free circulating Cortisol levels, making salivary Cortisol more responsive to research on subtle stressors, rather than the extreme diseases noted by blood testing. Urinary testing allows us to see the metabolism of hormones, but does not effectively represent the free circulating hormone levels.