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Hormone Treatments in Chronic and Intractable Pain

An Emerging Practice
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Recent research by the author and others shows that intractable pain that is constant is a severe stressor on the hypothalamic-pituitary-adrenal axis.5-9 For some indeterminate time, this profound stress causes elevated serum cortisol concentrations. Unfortunately, the pituitary and adrenal glands cannot keep pace with the stress of intractable pain, and the adrenal gland finally exhausts.6,9 Exhaustion is manifested by low serum cortisol concentrations.

To determine the point in the stress-exhaust cycle of a new intractable pain patient, a serum cortisol and pregnenolone concentration should be routinely determined in every new patient. Table 4 gives the interpretation of the results. If a patient demonstrates high or low serum cortisol concentration, vigorous pain control with opioids will likely normalize cortisol serum levels.9 Total cortisol replacement is rarely required.

Test Result Interpretation
High Cortisol & Pregnenolone Concentration Severe, uncontrolled, constant pain
Either Cortisol or Pregnenolone Concentration is elevated Moderate pain or some pain control
Normal Cortisol and Pregnenolone Mild pain or good control of pain
Low Serum Cortisol or Pregnenolone Severe constant pain which is uncontrolled with adrenal exhaustion

Table 4. Serum Adrenal Screening of an Intractable Pain Patient

There are two clinical situations where exogenous, systemic (not local corticoid injection) corticoids may be helpful. One is autoimmune diseases such as systemic lupus erythematosis which requires exogenous corticoids for control of underlying disease and not pain, per se. The second is the exacerbation or destabilization of an intractable pain patient who has been in treatment for an extended period. In this case the patient complains of return of severe pain, suffering, disability, insomnia, and usually, a house or bedbound state. When a relapse or destabilization occurs, a serum cortisol concentration should be obtained. If high, the pain control regimen is inadequate. If low, short-term systemic corticoid administration is indicated.

In addition to cortisol testing, the pain treating physician can also do a therapeutic test by giving an injection or one-time oral dose of a corticoid to see if a clinical response is obtained. For example, if a case of acute flare or destabilization of arachnoiditis, fibromyalgia, headache, or radiscolopathy is due to inflammation, a loading dose of oral prednisone (10 to 20mg) or injectable corticoid will provide a positive response within 12 hours if there is adrenal insufficiency and low serum cortisol levels.

Long-term maintenance with corticoid preparations is seldom necessary in chronic or intractable pain patients, but short-term administration for flares and destabilization is probably under-utilized. If long-term cortisone replacement is necessary, an endocrine consultation may be helpful.


Severe intractable pain may alter thyroid function and produce a variety of abnormal thyroid tests.7,38 In this situation intractable pain appears to be like other severe illnesses that may suppress a variety of pituitary hormones including thyroid stimulating hormone (TSH). One report suggests that low serum thyroid is a way to differentiate bonafide severe pain from malingering.38 The condition in which there is suppressed thyroid output in severe illness is sometimes called “euthyroid sick syndrome,” “non-thyroid illness,” or “low T3 syndrome.”39

Although no controlled or systematic studies have been reported, the author believes that reasonably well-controlled pain allows adequate pituitary release of TSH resulting in normal serologic tests for T3 and T4. A trial of thyroid replacement can be attempted with considerable safety if the patient demonstrates low T3 or T4. Plain desiccated thyroid in a dose of one to three grains is recommended. Although severe pain, like other severe illnesses, commonly demonstrate low T3 or T4 in serum, exogenous administration has not been reported to be of significant benefit except in post myocardial infarction patients. No side-effects of treating, however, have been reported, so a clinical trial with low dosages of thyroid for three to six weeks can be attempted.


Severe chronic or intractable pain are profound stressors which deplete many hormones. Additionally, the underlying cause of pain — particularly autoimmune and inflammatory diseases — may produce chronic illness which additionally depresses or exhausts certain hormones. To compound problems, many therapeutic pain control agents including opioids and neuropathic agents may deplete hormones. Laboratory testing easily detects deficiencies of pregnenolone, DHEA, androstenedione, thyroid, cortisol, and testosterone. While aggressive and effective pain control will normalize most hormone deficiencies, replacement of some may be necessary. Some hormones, particularly pregnenolone, GABA, testosterone, chorionic gonadotropin, and human growth hormone may be able to provide some permanent healing of nerves, muscle or other tissue and provide permanent pain reduction. Hormone testing and treatment is an emerging practice which should progressively become an integral component of pain treatment.

Last updated on: May 16, 2011