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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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Recommended Screen
A single, early-morning cortisol test is the easiest and most practical screen for most practitioners. All communities in the United States, big and small, have a lab or blood-drawing station that can perform or acquire a cortisol screen. If a practitioner desires, he or she may concomitantly order other endocrine tests, such as serum testosterone, pregnenolone, or ACTH, which will give a more complete picture of the pain patient’s HPA axis. Saliva testing and performing multiple screens, such as in the early morning and late afternoon, are also perfectly acceptable. When done by a sophisticated practitioner, a subtle change in diurnal secretion, such as high serum cortisol in the afternoon, may be a tip-off that pain control should be improved. Table 2 shows results of 40 consecutive patients screened for cortisol levels. These patients described their pain as constant and disabling and were on low dosages of opioids or none at all.

Very Low Cortisol Level—Danger Sign
A patient with a very low cortisol level, less than 1.0 mg/dL, may present in a vegetative, catabolic state. This state can be life threatening if immediate pain control and temporary corticoid support are not administered. Unfortunately, severe hypocortisolemia may present very subtly and not be suspected. In fact, these patients may initially give the impression that they are uncooperative, unmotivated, depressed, psychotic, or drug seeking. For example, very low cortical levels interfere with mentation, so the patient may not respond rapidly or even sensibly to a practitioner’s questions.57-61 The patient may sit very still, stare straight ahead, and speak in almost inaudible tones. Physical exam may show hypotension, tachycardia, and muscle wasting. Recent weight loss may have occurred.

An adequate cortisol serum concentration is required for opioid effectiveness, as this hormone helps maintain the blood–brain barrier and enhance receptor binding.52,53 The patient may perceive this neurodeficiency as a need for more opioids.

Set up a system in your practice to review cortisol laboratory reports as soon as possible. Regard a serum cortisol concentration below 1.0 mg/dL as an emergency. On more than one occasion, I have missed the subtle signs and symptoms of hypocortisolemia during the history and physical, and not until the laboratory report crossed my desk did I realize I had a serious problem on my hands. The following case is illustrative and somewhat humiliating.

Case Example
A 29-year-old, unemployed female registered nurse was referred for poor pain control due to fibromyalgia. At the time of initial evaluation, she gave very vague answers to questions. Her blood pressure was 105/70 mm Hg, and she had a pulse rate of 110 beats per minute. My initial impression was that she was a depressed patient simply looking for more opioids. Not until the early morning cortisol screen came back at “less than 1.0 mg/dL” did I realize how far off my initial impression had been. The patient was called back to the clinic and given methylprednisolone 80 mg intramuscular and started on prednisone 5 mg four times a day for 2 weeks. Her opioid dosage was progressively raised over 60 days to the point that her depression lifted, her pain was controlled, and she returned to work. Within 60 days, her serum cortisol concentrations were normal and ranged from 10 to 15 mg/dL.

Recurrent High Cortisol Levels
In the last century, Harvey Cushing, MD, described the serious medical complications of pituitary basophilic adenomas and hypercortisolemia. The chronic exposure of excess serum cortisol in chronic pain patients is no different from Cushing’s syndrome and constitutes one of the most serious health risks of poorly treated pain. Such patients may develop any of the classic complications of Cushing’s syndrome, including hyperlipidemia, diabetes, osteopenia/osteoporosis, dental decay, weight gain, and mental deterioration (see Table 4).59-67

It is essential to know that hypercortisolemia can be intermittent and still cause complications. It does not have to be continuous. Frequent acute flares or episodes of breakthrough pain may elevate cortisol levels.33,35 Unfortunately, the various complications that high serum cortisol may induce have other causes. For example, weight gain and diabetes may be due to diet and inability to move. For these reasons, serum cortisol screening may differentiate causation and should be done periodically. One condition to which I wish to call attention is one I have tragically observed on too many occasions in patients with severe chronic pain. With continued exposure to hypercortisolemia, these patients may develop osteoporosis with vertebral collapse.

Case Example
In 2001, a 50-year-old woman with facial neuropathies secondary to trauma had an early-morning serum cortisol of 28 mg/dL. A repeat screen within 6 months revealed a normal cortisol serum concentration. Consequently, little attention was paid to the original screen. The patient resisted most pain medications, preferring to “tough out” her flares. A repeat cortisol screen about 3 years after the first screen was also elevated (25 mg/dL). Without warning, her spine collapsed about 5 years after her first cortisol screen. She now has required multiple spine surgeries, including fusion and rod placement. Osteoporosis was quite obvious by bone scan. She is now on an osteoporosis preventive regimen and a vigorous medical regimen to control her baseline and pain flares. Cortisol screening is routine, and her levels are in normal range.

How Often Should Cortisol Screening Be Done?
I recommend every 90 to 120 days if the patient has ever had an abnormal (high or low) screen. Otherwise, it should be done every 6 to 12 months.

Opioid Suppression of Cortisol
Opioids usually, but not always, spare cortisol in chronic pain patients.68,69 For unknown reasons, opioids most commonly suppress testosterone serum levels in patients with chronic pain.54,56 If a patient on opioids happens to have a low cortisol level, it is usually because the opioid dosage is too low and not due to opioid suppression. If the patient reports good pain control at the time the serum cortisol is low, however, cortisol may have to be replaced. I have successfully replaced cortisol with bioavailable cortisone, prednisone, and fluorinated corticoids. Pregnenolone supplements are also recommended, as pregnenolone is the precursor of cortisol.

Last updated on: June 5, 2017
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