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Identifica tion and Management of Cardiac -Adrenal-Pain Syndrome

Severe, chronic, under-treated pain may produce cardiac and adrenal complications, that in some pain patients, can lead to premature death.
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Table 1. Cardiac-Adrenal Abnormalities in 91 Severe, Chronic Pain Patients
Abnormalities # %
Hypertension above 130/90 (mm/Hg) 60 65.9%
Pulse Rate 84 per minute or above 46 50.5%
Elevated Serum Cortisol above 20ug/dl 28 30.8%
Low Serum Cortisol below 5ug/dl 15 16.5%
Erythrocyte Sedimentation Rate (ESR) above 20 (mm/hr) 30 33.0%
Physiologic Abnormalities No. with Abnormality Mean Before Treatment (SD) Mean After Treatment (SD) Statistical Significance
High systolic blood pressure (mm/Hg) 28 152.3 ± 19.5 136.3 ± 19.2 t = 3.51; df = 27; p< 0.01
High diastolic blood pressure (mm/Hg) 28 98.4 ± 16.3 63.1 ± 10.8 t = 5.41; df = 27; p< 0.01
Elevated pulse rate per minute 21
93.1 ± 7.9 63.9 ± 15.0 t = 2.80; df = 20; p< 0.01
Low serum cortisol concentration (ug/dl) 7 3.6 ± 1.0
8.6 ± 1.6 t = 4.02; df = 6; p< 0.01
High serum cortisol (ug/dl) 12 24.5 ± 2.6 16.2 ± 6.5 t = 4.67; df = 11; p< 0.01
Low serum pregnenolone (ng/dl) 18 13.6 ± 3.0 50.1 ± 52.7 t = 3.0; df = 17; p< 0.01
High erythrocyte sedimentation rate (mm/hr) 10 33.9 ± 10.3 10.5 ± 7.4 t = 6.0; df = 9; p< 0.01
Table 2.


Fifty, (50) consecutive patients, some of whom were in the first study, were selected for investigation. Criteria and procedures described in the identification study were identical except serum pregnenolone was added as a second screen for adrenal hormone complications. Pregnenolone is the precursor of all glucocorticoids and sex hormones including progesterone, estrogen, and testosterone. Additionally, it enters the serum, crosses the blood-brain barrier, and acts as a hormone by attaching to receptors in nervous tissue.

Complications of Excess and Deficient Cortisol
Pregnenolone Serum Levels
Decalcification of bone and teeth (osteoporosis)
Hyperglycemia (diabetes)
Muscle wasting weakness, depression
Truncal obesity
Poor pain control
Muscle wasting
Memory-attention deficit
Immune abnormalities
Loss of libido, Weight loss
Note: “Excess” is similar to Cushing’s Disease and “Deficient” is similar to Addison’s Disease
Table 3.

After screening in the first week of treatment, repeat assessment of these same abnormalities was done after 90 or more days of adequate pain treatment. All patients had severe pain over a period ranging from 3 to 22 years and all had failed multiple, non-opioid pain treatments. There were 18 (36%) males and 32 (64%) females and the patients’ ages ranged from 36 to 68 years. At the time of referral, patients were all being treated with 4-8 daily dosages of hydrocodone or codeine-acetaminophen compounds with a daily morphine equivalency estimated in the range of 20 to 40mg. There was a high prevalence of physiologic abnormalities detected in these patients. Highest prevalence was hypertension (56%) and lowest prevalence was elevated ESR (20%). Forty-eight of the 50 (96%) patients demonstrated at least one physiologic abnormality (see Table 2).

Figure 2. Blood Pressure and Pulse at-home patient monitoring to be completed by patient and family.

After the initial screens were done, treatment was started with a long-acting opioid preparation consisting of methadone, fentanyl transdermal, or a sustained release preparation of oxycodone or morphine. Additionally, patients received one or two short-acting opioids for breakthrough pain. These consisted of fentanyl transmucosal citrate, hydrocodone, oxycodone, morphine, or hydromorphone. Estimated daily morphine treatment equivalency ranged from 400 to 1000mg. Other components of treatment included stretching exercises, participation in patient support groups, topical analgesics, and nutritional supplements. All patients attended an outpatient clinic on a monthly basis at which time daily opioid dosage was titrated upward to maximally suppress pain or, alternately, reduced if sedation was apparent.


Following pain treatment of approximately 90 or more days, physiologic abnormalities normalized in most cases. The percentage reduction of patients who demonstrated a physiologic abnormality before and after 90 days of treatment was statistically significant in all instances. Reductions in the percentage of patients with a physiologic abnormality were as follows: 1) hypertension was reduced from 56% to 28% of the patients; 2) tachycardia was reduced from 42% to 18%; 3) elevated morning cortisol concentration decreased from 24% to 4%; 4) low serum cortisol concentration almost disappeared with treatment (14% to 2%); 5) low serum pregnenolone concentration was reduced from 36% to 6%; and 6) elevated ESR was reduced from 20% to 6% of the patients (see Table 2).

Concordant with these reductions, the mean values of physiologic abnormalities showed a significant trend toward normalization (see Table 2). Mean systolic and diastolic blood pressure, elevated cortisol serum concentration, and elevated ESR were significantly lowered after treatment. Similarly, low mean concentrations for serum cortisol and pregnenolone moved closer to normal at the end of treatment (p<0.01).

Last updated on: May 16, 2011