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November 2012 Letters to the Editor

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Case: Chronic Pelvic Pain; Cortisol Replacement

Dear Dr. Tennant,
I have two questions. First, I have a patient with chronic pelvic pain and interstitial cystitis. She had been worked up for years without relief. Many medications and supplements worsen her pelvic pain. She cannot sleep for more than one hour at a time and simple tasks such as walking are excruciating. She is unable to have sexual relations with her husband and any [such] relations cause pain for many days afterward. I appreciate your help in managing my patient. Any comments, suggestions, or ideas would be much appreciated.

My second question is about how high can we go on cortisol replacement. Also, what do you recommend as far as testing and monitoring levels of cortisol?

Thank you,

Azza Kenawy, MD
West Chester, Pennsylvania

Dear Dr. Kenawy,
Your patient with pelvic pain is, tragically, suffering from a condition that is becoming somewhat common in pain practice. Most of these patients appear to me to have a progressive, debilitating autoimmune disease, and they are most difficult to manage. I’ve found that some gynecologists and urologists have therapeutic agents and measures that help. My guess is that your patient has already seen these specialists and attempted the standard neuropathic agents such as duloxetine (Cymbalta), gabapentin, and pregabalin (Lyrica).

In all the patients I’ve seen with these problems there is a genetic basis. Many were sickly as a child and have cytochrome P450 defects. Implanted electrostimulation devices are worth a trial as are the oral and even intrathecal opioids.

If all else fails, I attempt to find an injectable opioid that relieves pain. Hydromorphone or morphine may be required since these opioids bypass the cytochrome P450 system. I bring patients into my clinic and give small, progressive, subcutaneous dosages to find the one that relieves pain. Until some pain relief is attained, patients will hardly participate in any other kind of therapeutic endeavor.

I’m hopeful that readers of this case will send us some ideas. We urgently need to have some new direction on patients who have developed autoimmune diseases, which cause excruciating pain and horrible suffering.

Regarding, corticol replacement, first, I recommend that pain practitioners use plain hydrocortisone (Cortef) to treat low cortisol levels. Hydrocortisone rapidly metabolizes to cortisol, so you can easily monitor replacement efforts with a serum cortisol level. Organic chemists have developed a bewildering number of modified adrenocorticosteroids including prednisone, methylprednisolone, and dexamethasone. These compounds are much more potent than plain hydrocortisone, and they have two major problems. First, they don’t convert to cortisol, so blood levels of cortisol can’t be used as a therapeutic guide. Second, they rapidly suppress adrenocorticotrophin hormone and cortisol levels.

Total replacement dosage in the average adult is about 20 to 30 mg of hydrocortisone per day. In pain patients, a dosage of 5 or 10 mg per day may be adequate. I have had to give 60 mg per day to one man who weighs more 250 pounds to raise his cortisol serum level into the normal range
(>5 mcg/dL).

Keep in mind that we are only doing partial replacement in pain management because the adrenal is still functioning. In real Addison’s disease, total replacement is required, since the adrenals aren’t capable of normal function. Also, cortisol replacement can often be stopped once pain is controlled.

There is no fear of pituitary-adrenal suppression with replacement dosages of plain hydrocortisone unless serum levels of cortisol remain above the normal range for several weeks. The same can’t be said when the potent synthetic compounds such as prednisone and methylprednisolone are used.

Forest Tennant, MD, DrPH


Pain Patients With CYP450 Defects

Dear Dr. Tennant,
I read your recent article on cytochrome P450 [CYP450] testing with great interest.1 Are you able to estimate what proportion of your overall intractable pain practice is represented in the 66 patients?

I had a practice similar to yours in Delray Beach, Florida, until about 18 months ago, but was victimized by a diverting patient and am now fighting criminal charges and for the return of my license.

Barry Schultz, MD
Delray Beach, Florida

Dear Dr. Schultz,
At this time I can’t be sure of the prevalence of CYP450 defects in the intractable pain population. I have come to believe, however, that most pain patients who require very high opioid dosages for relief do so because they have CYP450 defects. It is for this reason that I now recommend that patients who require >150 mg equivalent of morphine per day be genetically tested to validate that there is a good reason for the high opioid dosage. One thing is clear: there are legitimate pain patients who require high-dose opioids, and the vast majority of these patients have genetic, metabolic defects. I also believe these patients need to be in intractable pain practices that can and will closely follow and monitor the patient.

Forest Tennant, MD, DrPH


Claiming Pain For Personal Gain

Dr. Tennant,
As most disability claimants that I represent have chronic pain that is difficult to “prove” to an adjudicator, I am very interested in your guidance on the laboratory evidence that may provide objective findings for their chronic pain (and severity). For example, I am excited at the possibility of documenting chronic pain by asking their doctors to provide information regarding the characteristic clinical and diagnostic signs you talk about for centralized pain. Or, if their chronic pain is not central, what objective measures do you think should be convincing? To also include sympathetic discharge signs? Right now, we ask doctors to simply give their opinion that a patient’s pain would prevent working an 8-hour day.

Thanks very much.

Jeff Hadley, PhD
Baltimore, Maryland

Dear Dr. Hadley,
You raise the critical issue of malingering and claiming pain for personal gain. The time is fast arriving when some objectivity to this issue must be standard.

The notion that we need some objective evidence to validate severe pain is extremely controversial. As you have suggested in your letter, many parties want to simply evaluate and judge pain solely by the patient’s word.

From my vantage point, I believe I can always find some objective evidence of severe, chronic pain after it has centralized. Be clearly advised that the dividing line between centralized and non-centralized pain is not crystal clear. Some patients have both. Severe pain, central or non-central, that requires daily opioid control, however, should show some of the objective measures noted above. Beginning in this issue, we introduce, for example, the concept of adrenocorticotropin hormone (ACTH) as a biomarker for severe pain.

Last updated on: November 30, 2012
First published on: November 1, 2012