Cortisol Screening in Chronic Pain Patients

Screening for cortisol serum levels can give treating clinicians an insight into whether patients with chronic pain are at risk for diabetes, hyperlipidemia, and osteoporosis.
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Why screen chronic pain patients for cortisol levels? An abnormal serum concentration is an excellent biologic marker for uncontrolled pain.1-8 It can also give you a good idea about whether the patient is in a depressed, catabolic state or if the patient is at high risk for excess corticoid complications, including osteoporosis, dental decay, hypertension, hyperlipidemia, and diabetes.9-26 Most critical, to clinicians, cortisol serum levels should be viewed as an essential biologic marker to guide treatment.1,7,8

Enough information about pain and its effects on the endocrine system has accumulated to provide a basis for specific clinical interpretations and recommendations.27-33 This article provides simple guidelines to begin cortisol screening of your patients with chronic pain.

Good Indicator of Stress
Cortisol is an end product of hypothalamic-pituitary-adrenal (HPA) stimulation (see Table 1, page 44). Often called an “axis,” this biologic system is stimulated by any inflammatory, emotional, or physical stress.34,35 There is no greater stress than pain, and chronic pain may be accompanied by neuroinflammation.28,36-42 When pain occurs, the axis is stimulated, causing corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), catecholamines, and serum cortisol to rise.43-47 Interestingly, testosterone may lower during acute pain.1,4,29-33 Cortisol may rise in any acute pain episode, including a breakthrough pain flare in a patient with chronic pain.33,35 When acute pain turns chronic, the stimulation of the HPA axis continues, resulting in elevated serum cortisol levels.1,4,29,30 The natural purpose of elevated cortisol is activation of the body’s immune defenses and healing to eliminate the cause of pain and facilitate tissue recovery.48-53 Uncontrolled and unresolved severe pain may overstimulate and later impair the HPA axis to the point that normal adrenal cortisol secretion does not occur. In this situation, cortisol serum levels drop below normal.1-5

Most endocrine studies, including those on cortisol, have been done in patients with fibromyalgia and rheumatoid arthritis.29-32 Some studies also have examined patients with headache, osteoarthritis, and lumbar spine disease.38,48 Different studies show variability in the hypothalamic-pituitary response to chronic pain, with some showing hypo- or hyperresponsiveness of CRH and ACTH.30,32,37 This difference is best explained by the long time course, usually a lifetime, of chronic pain and the great variations in neuroinflammation and neuroplasticity that are present when chronic pain becomes central in nature. Despite variability in pain causation and varying effects of chronic pain on the hypothalamus and pituitary gland, the effects of chronic pain on the adrenal gland show a rather consistent pattern. In the early phase of severe, chronic pain, adrenal hypersecretion with elevated serum cortisol concentration is present.1-5 Later, low cortisol serum levels occur because of pain’s suppression of CRH and ACTH in the hypothalamus and pituitary gland.2,4,28,29,32,37 Exactly how severe chronic pain suppresses CRH and ACTH in the hypothalamus and pituitary gland is not known, but it clearly occurs.

To the practitioner, the message is clear. Severe, uncontrolled acute or chronic pain initially causes hypersecretion of adrenal cortisol, resulting in an elevated serum level, which is later followed by HPA suppression, resulting in a low cortisol serum concentration. Serum cortisol concentrations that are too high or too low are biologic markers that call for aggressive pain management to bring the cortisol level into normal range (see Table 2).

Who Should Be Screened?
To date, testosterone testing and replacement are the only endocrine measures that have emerged to any extent in pain practice.54-56 Cortisol screening should be a routine measure in any patient with chronic pain who claims his or her pain to be constant or persistent and severe enough to require daily opioid treatment. Patients who experience mild or episodic forms of chronic pain, demonstrate normal immunologic markers such as erythrocyte sedimentation rate, and require only nonopioid medication are likely to maintain normal endocrine function and normal serum cortisol levels and need not be screened.2,8,30-32,40,48

The patients with chronic pain who most likely will have an abnormal (high or low) cortisol serum concentration are those who have central pain. This form of pain recently has been referred to as “maldynia” in that the pain is constant and is not provoked or worsened by any stimulus such as movement, pressure, or stress. Patients will complain of insomnia and periodic episodes of allodynia (pain to light touch) and/or hyperalgesia (extra pain on pressure).

Patients usually will complain of poor pain control and report that they receive little or no help from a variety of therapeutic modalities, such as nonopioid medications and physical therapy. When in doubt, cortisol screening is highly recommended as an adjunctive evaluation tool to a standard history and physical examination.

Patients on opioids who complain of poor pain control also should be screened, because adrenal corticoids are necessary for opioid receptor binding and maintenance of the blood–brain barrier.52,53 In rare cases, the drop in serum cortisol even can be life threatening. Severe hypocortisolemia lower than 1.0 mg/dL will result in a clinical picture that may include hypotension, slow movement and mentation, and muscle wasting (see Table 3). The patient usually sits in a rather fixed position, stares straight ahead, and speaks very softly. Emergency opioid administration to relieve pain is a necessity and temporary cortisol replacement may be essential.

When Should Patients Be Screened?
Screening should occur as soon as you determine that a patient with chronic pain has constant pain and doesn’t respond well, if at all, to some standard pain treatments. Any delay puts the patient at risk for hyper- and hypocortisolemia.

First published on: January 1, 2012