Cortisol Testing

Chapter eleven of Wilson's book covers the different cortisol testing methods available for cortisol in saliva, blood, and urine, as well as the ACTH stimulation test.  Wilson favors the 4 sample salivary cortisol test as the easiest and most convenient method, with the added advantage that salivary testing can done at home without a doctor's prescription.

Left Image: Cortisol Chemical Structure Courtesy of Wikimedia.

Another chapter in the book covers treatment and recovery from adrenal fatigue with modification of diet and lifestyle, and diet, avoiding food allergies, and the use of hormone supplements and dietary supplements.  He also weighs the use of Cortef (cortisol) vs. adrenal cortical extracts. 

Results from Years of Chronic Stress

Adrenal fatigue is the net result of years of continuous high cortisol output by the adrenals caused by chronic stress from job, family, illness, injury, and poor diet and lifestyle associated with high-tech modern living. After years of chronic stress, the two small triangular supra-renal glands poop out, and we become another casualty of adrenal fatigue, the 21st century epidemic. Since mainstream doctors can't seem to help, either ignoring the syndrome, or prescribing anti-depressants for it, this self-help book may be a life-saver.

Definition of Adrenal Fatigue: 

"Adrenal Fatigue is a collection of signs and symptoms that results from low function of the adrenal glands. The paramount symptom is fatigue that is not relieved by sleep.  The syndrome may be caused by intense or prolonged stress, or after acute or chronic infections, especially respiratory infections such as influenza, bronchitis or pneumonia....People suffering from Adrenal Fatigue often have to use coffee, colas and other stimulants to get going in the  morning and to prop themselves up during the day. "Courtesy of James L. Wilson web site.

Anxiety
Asthenia - lack of, or loss of strength, generalized weakness
Asthma
Autoimmune problems
Bronchitis - recurrent, chronic or slow recovery from
Burnout
Chemical Sensitivity
Chronic fatigue syndrome (CFS)
Chronic infections,
Chronically run down - with early morning fatigue and low blood pressure
Chronic mental and/or physical exhaustion
Cravings for carbohydrates, sweets or salt
Depression
Fatigue - severe, disabling early morning fatigue
Feeling tired despite sufficient hours of sleep
Fibromyalgia
Hair loss
Hypoglycemia
Immune System dysfunction - frequent illnesses
Insomnia - or non-restful sleep
Low Blood Pressure
Nervous breakdown (nervous exhaustion)
Pneumonia
Respiratory infections - recurrent, chronic or slow recovery from
Rheumatoid arthritis
Reliance on stimulants like caffeine
Slow recovery following acute infectious diseases, especially influenza, pneumonia, or other respiratory infections
Weight gain

The  Adrenal Glands Make the Cortisol

Left Graph: Patient samples are all in the channel    Right Graph: Adrenal Fatigue is Obvious

Nutritional Supplement Program for Adrenal Fatigue and Recovery

The keystone of the treatment program is a nutritional supplement program to restore adrenal function that includes vitamin C, B5, magnesium, biotin and adaptogenic herbs.  We use a product called Adapt from Interplexus along with a high quality multivitamin.  Another Interplexus product, Seriphos, is useful to correct the reversed pattern of high cortisol at night which may cause insomnia.  Recovery takes about 6 weeks.

Cortef for Severe Cases of Adrenal Fatigue

In very severe cases of adrenal failure, Cortef tablets are available and produce a dramatic improvement in clinical condition.  See the book, Safe Use of Cortisol by William M Jefferies.  Cortef is the name for bio-identical cortisol which is widely available at the local drug store.  Synthetic forms of cortisol such as prednisone and dexamethasone are not recommended as they can be associated with adverse side effects.

Left Image courtesy of William Mck Jefferies MD

Other Useful Treatments Routinely Used:

Avoid excess caffeine, refined carbohydrates, alcohol and sugar.
Get plenty of sleep.
Take steps to reduce stress with gentle exercise, meditation, and yoga.
Bioidentical hormones as determined by lab profile.

Jacob Teitelbaum MD

Another excellent book is From Fatigued to Fantastic, by Jacob Teitelbaum MD, which covers adrenal fatigue and other related conditions causing chronic fatigue.

Left Image Courtesy of Jacob Teitelbaum MD
  

Cortisol's Relation to Thyroid Function - Avoiding A Common Pitfall

Low cortisol adrenal fatigue will place the body into a protective state in which metabolic rate is reduced to cope with the low cortisol production.  The easiest way to reduce metabolic rate is to reduce thyroid function, usually by shunting thyroid hormone production into the reverse T3 pathway.  This, in essence, inactivates the thyroid hormone and creates a functional low thyroid state.  Thyroid labs will show a low thyroid state, and giving thyroid hormone in this scenario is a common pitfall to be avoided.  Giving thyroid hormone to a patient with low cortisol adrenal fatigue will only make the patient feel worse.  The low adrenal function must be addressed first before attempting to raise thyroid levels.  This is done with a salivary cortiol test (4 samples) and a nutritional supplement program over 6 weeks as described above. 

In the event the patient is already taking thyroid hormone medication which doesn't seem to be working or is not tolerated, then the most likely issue is low cortiol adrenal fatigue.  Once this is addressed, the patient will be able to tolerate thyroid medication.

A discussion of low adrenal function and thyroid can be found at Stop The Thyroid Madness.

Article by Kent Holtorf MD on Adrenal Fatigue:

Hypothalamic_Pituitary_Adrenal_HPA_Dysfunction_Chronic_Fatigue_Syndrome_Fibromyalgia_Kent_Holtorf_2008.pdf
199.1 KB

Thanks and credit goes to Kent Holtorf dor this excellent article on HPA axis dysfunction in CFS/FM that was published in 2008 Journal of Chronic Fatigue Syndrome by Kent Holtorf MD. 


Jeffrey Dach MD
7450 Griffin Rd Suite 180/190
Davie, FL 33314
Phone: 954-792-4663
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Links and References:

1)Hypothalamic_Pituitary_Adrenal_HPA_Dysfunction_Chronic_Fatigue_Syndrome_Fibromyalgia_Kent_Holtorf_2008.pdf
199.1 KB


http://www.adrenalfatigue.org/
Adrenal Fatigue by James WIlson

http://coastherbal.com/web_standard/adrenal_stress.html
THE STANDARD Adrenal Stress: Measuring and Treating Thomas G. Guilliams Ph.D.

http://www.spinelife.com/pdf/AdrenalStress.pdf
THE STANDARD Adrenal Stress: Measuring and Treating Thomas G. Guilliams Ph.D.

http://www.medaus.com/p/200,516.html
Saliva Reference Summary
Copyright ZRT Laboratory (3-12-01) METHOD VALIDATION
For your convenience, a brief summary of published, scientific articles on saliva testing of hormones, particularly in reference to a comparison with blood serum testing, is provided below. These articles redress a common misconception among health care providers that there is little research to support the efficacy of saliva testing for hormonal imbalance. The summaries also serve to illuminate the substantial volume of clinical and scientific research that has in fact been published on the topic.

http://advan.physiology.org/cgi/content/full/31/1/110
ADV PHYSIOL EDUC 31:110-115, 2007
TEACHING IN THE LABORATORY A laboratory exercise to illustrate increased salivary cortisol in response to three stressful conditions using competitive ELISA
Mark F. Haussmann, Carol M. Vleck and Eugenia S. Farrar

http://www.biovit.hr/ibl/saliva/cortisol_e.pdf
Cortisol Physiology / Effects of Cortisol
• Enhancement of the catabolic part of the lipid and protein metabolism and the gluconeogenese
• antagonism to insulin
• inhibition of the inflammatory and allergic processes
• enhancement of the contractibility of the heart muscle and improvement of the peripheric microcirculation
• enhancement of water excretion by the kidneys
• enhancement of the production of gastric juice
• enhancement of the osteoporotic effect within the bones
• enhancement of the excitability in brain regions
• suppression of the hormone secretion of the anterior part of the pituitary gland (effect on the thyroid gland and the gonads)

http://www.jacemedical.com/store/low_cortisol.html
The Medical Evidence for Low Cortisol in Chronic Fatigue Syndrome!

http://www.cdc.gov/cfs/publications/clinical_10.htm
Attenuated morning salivary cortisol concentrations in a population-based sample of cases with chronic fatigue syndrome and well controls.
Nater UM, Maloney E, Boneva RS, Jones JF, Reeves WC, Heim C.
Journal of Clinical Endocrinology & Metabolism 26 December 2007 doi:10.1210/jc.2007-1747.

http://ajp.psychiatryonline.org/cgi/content/full/162/4/807
Am J Psychiatry 162:807-809, April 2005
Brief Report Enhanced Early Morning Salivary Cortisol in Neuroticism
Maria J. Portella, M.Sc., Catherine J. Harmer, D.Phil., Jonathan Flint, D.Phil., Philip Cowen, M.D., F.R.C.Psych., and Guy M. Goodwin, D.Phil., F.R.C.Psych.

http://archpsyc.ama-assn.org/cgi/content/full/57/1/38
Low Salivary Cortisol and Persistent Aggression in Boys Referred for Disruptive Behavior Keith McBurnett, PhD; Benjamin B. Lahey, PhD; Paul J. Rathouz, PhD; Rolf Loeber, PhD Arch Gen Psychiatry. 2000;57:38-43.

http://www.sav.sk/journals/endo/full/er0298f.pdf
IATROGENIC ADRENAL CORTEX FAILURE IN PATIENTS WITH STEROID DEPENDENT ASTHMA IN RELATION TO DIFFERENT METHODS OF GLUCOCORTICOID TREATMENT B. KOS-KUDLA ENDOCRINE REGULATIONS, Vol. 32, 99 ? 106, 1998

 http://bbh.hhdev.psu.edu/labs/bbhsl/PDF%20files/klein%20et%20al.%20cortisol%20and%20naltrexone.pdf
Sex Differences in Salivary Cortisol Levels Following Naltrexone Administration LAURA COUSINO LARRY D. JAMNER, JANEL ALBERTS, MATTHEW

http://bjp.rcpsych.org/cgi/content/full/184/2/136
Salivary cortisol response to awakening in chronic fatigue syndrome Amanda D. L. Roberts, PhD . The British Journal of Psychiatry (2004) 184: 136-141 Background There is accumulating evidence of hypothalamic—pituitary — adrenal (HPA) axis disturbances in chronic fatigue syndrome (CFS). The salivary cortisol response to awakening has been described recently as a non-invasive test of the capacity of the HPA axis to respond to stress. The results of this test correlate closely with those of more invasive dynamic tests reported in the literature; furthermore, it can be undertaken in a naturalistic setting. Aims To assess the HPA axis using the salivary cortisol response to awakening in CFS. Method We measured salivary cortisol upon awakening and 10, 20, 30 and 60 min afterwardsin 56 patients with CFS and 35 healthy volunteers. Results Patients had a lower cortisol response to awakening, measured by the area under the curve. Conclusions This naturalistic test of the HPA axis response to stress showed impaired HPA axis function in CFS.

http://www.virginiahopkinstestkits.com/cortisolzava.html
Cortisol Levels, Thyroid Function and Aging HOW CORTISOL LEVELS AFFECT THYROID FUNCTION AND AGING Interview with David Zava, Ph.D. Originally published in the John R. Lee, M.D. Medical Letter

 http://www.drmyhill.co.uk/article.cfm?id=266
Common Hormonal Problems in CFS - Adrenal  Underactive adrenal gland (DHEA and cortisol) If the pituitary gland is underfunctioning then the adrenal gland will also underfunction. However the gland itself may fail as a result of chronic stress. 

http://www.adrenalfatigue.org/
James Wilson, author of Adrenal Fatigue

http://www.adrenalfatigue.org/qa.php
Questionnaires. The questionnaires in this section are not intended to diagnose any illnesses. They are purely informational and may help you see if there is a problem you need to pay attention to or consult a doctor about.
Click on the questionnaire in blue below to you would like to take.
Burnout, Candida, Food and Environmental Intolerances

http://www.jacemedical.com/store/low_cortisol.html
The Medical Evidence for Low Cortisol in Chronic Fatigue Syndrome!
MEDICAL ABSTRACTS

http://www.cdc.gov/cfs/publications/clinical_10.htm
Attenuated morning salivary cortisol concentrations in a population-based sample of cases with chronic fatigue syndrome and well controls.
Nater UM, Maloney E, Boneva RS, Jones JF, Reeves WC, Heim C.
Journal of Clinical Endocrinology & Metabolism 26 December 2007 doi:10.1210/jc.2007-1747.

http://ajp.psychiatryonline.org/cgi/content/full/162/4/807
Am J Psychiatry 162:807-809, April 2005
Brief Report Enhanced Early Morning Salivary Cortisol in Neuroticism
Maria J. Portella, M.Sc., Catherine J. Harmer, D.Phil., Jonathan Flint, D.Phil., Philip Cowen, M.D., F.R.C.Psych., and Guy M. Goodwin, D.Phil., F.R.C.Psych.

http://www.intlhormonesociety.org/ref_cons/Ref_cons_3_mild_glucocorticoid_deficiency.pdf
International Hormone Society . Uses of Cortisol references

http://archpsyc.ama-assn.org/cgi/content/full/57/1/38
Low Salivary Cortisol and Persistent Aggression in Boys Referred for Disruptive Behavior Keith McBurnett, PhD; Benjamin B. Lahey, PhD; Paul J. Rathouz, PhD; Rolf Loeber, PhD Arch Gen Psychiatry. 2000;57:38-43.

http://www.sav.sk/journals/endo/full/er0298f.pdf
IATROGENIC ADRENAL CORTEX FAILURE IN PATIENTS WITH
STEROID DEPENDENT ASTHMA IN RELATION TO DIFFERENT
METHODS OF GLUCOCORTICOID TREATMENT. B. KOS-KUDLA ENDOCRINE REGULATIONS, Vol. 32, 99 ? 106, 1998

http://bbh.hhdev.psu.edu/labs/bbhsl/PDF%20files/klein%20et%20al.%20cortisol%20and%20naltrexone.pdf
Sex Differences in Salivary Cortisol Levels Following Naltrexone Administration1
LAURA COUSINO KLEIN2LARRY D. JAMNER, JANEL ALBERTS, MATTHEW D. ORENSTEIN, AND LINDA LEVINE

http://bjp.rcpsych.org/cgi/content/full/184/2/136
Salivary cortisol response to awakening in chronic fatigue syndrome Amanda D. L. Roberts, PhD

The British Journal of Psychiatry (2004) 184: 136-141 Background There is accumulating evidence of hypothalamic—pituitary — adrenal (HPA) axis disturbances in chronic fatigue syndrome (CFS). The salivary cortisol response to awakening has been described recently as a non-invasive test of the capacity of the HPA axis to respond to stress. The results of this test correlate closely with those of more invasive dynamic tests reported in the literature; furthermore, it can be undertaken in a naturalistic setting.  Aims To assess the HPA axis using the salivary cortisol response to awakening in CFS.   Method We measured salivary cortisol upon awakening and 10, 20, 30 and 60 min afterwardsin 56 patients with CFS and 35 healthy volunteers.
Results Patients had a lower cortisol response to awakening, measured by the area under the curve.

Conclusions This naturalistic test of the HPA axis response to stress showed impaired HPA axis function in CFS.

http://www.virginiahopkinstestkits.com/cortisolzava.html
Cortisol Levels, Thyroid Function and Aging HOW CORTISOL LEVELS AFFECT THYROID FUNCTION AND AGING Interview with David Zava, Ph.D. Originally published in the John R. Lee, M.D. Medical Letter

http://www.drmyhill.co.uk/article.cfm?id=266
Common Hormonal Problems in CFS - Adrenal Underactive adrenal gland (DHEA and cortisol) If the pituitary gland is underfunctioning then the adrenal gland will also underfunction. However the gland itself may fail as a result of chronic stress. 

http://www.drpressman.com/library/view.html?id=78
The Use Of Adrenal Cortical Extracts In Adrenal Fatigue
by James L. Wilson DC, ND, PhDWhat Is Hypoadrenia and Adrenal Fatigue?Wilson, James L. ND, DC, PhD. Adrenal Fatigue: The 21st Century Stress Syndrome Smart Publications, Petaluma CA, 2001

http://www.ncbi.nlm.nih.gov/pubmed/12377295
Tsigos C, Chrousos GP.Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002 Oct;53(4):865-71.

http://ajp.psychiatryonline.org/cgi/content/full/160/9/1554
Raison CL, Miller AH. When not enough is too much: the role of insufficient glucocorticoid signaling in the pathophysiology of stress-related disorders. Am J Psychiatry. 2003 Sep;160(9):1554-65.

http://www.biodia.com/TechnicalCharts/ChronicStresschart.pdf
Chronic Stress Response Chart

http://www.biodia.com/TechnicalCharts/SteroidalHormonechart.pdf
Steroidal Hormone Principle Pathways
(Understanding Pregnenolone Steal, the Preferential Pathway Under Chronic Stress)

http://www.drlam.com/A3R_brief_in_doc_format/adrenal_fatigue.cfm
Cortisol (The Hormone of Death)

The most important anti-stress hormone in the body is cortisol. Cortisol protects the body from excessive stress by:

Normalizes blood sugar - Cortisol increase blood sugar level in the body, thus providing the energy for the body to physically escape threat of injury  in order to survive. Cortisol works in tandem with insulin from the pancreas to provide adequate glucose to the cells for energy. More energy is required when the body is under stress from any source, and cortisol is the hormone that makes this happens. In adrenal fatigue, more cortisol is secreted during  the early stages. In later stages ( when the adrenal glands become exhausted), cortisol output is reduced, and blood sugar balance becomes a problem.

Anti-inflammation Response - Cortisol is a powerful anti-inflammatory agent.  When we have a minor injury or a muscle strain, our body's  inflammatory cascade is initiated, leading to swelling and redness commonly seen when a ankle is sprained or an insect bite. Cortisol is secreted as part of the anti-inflammatory response. It's objective  is to remove and prevent swelling and redness of nearly all tissues. These anti-inflammatory responses prevent mosquito bites from enlarging, bronchial tress and eyes from swelling shut from allergies, and swelling from being too intense.

Immune System Suppression - People with high cortisol levels are very much weaker from the immunological point of view. Cortisol influences most cells that participate in the immune reaction, especially white blood cells. Cortisol suppresses white blood cells, natural killer cells, monocytes, macrophages, and mast cells. It also suppresses  the auto-immune system response to foreign insult.

Vaso-constriction - Cortisol contracts mid-size arteries. People with low cortisol (as in advance stages of adrenal fatigue) have low blood pressure and reduced reactivity to other body agents that constrict blood vessels. Cortisol tends to increase blood pressure that is moderated by calcium and magnesium.

Physiology of Stress - People with adrenal fatigue cannot tolerate stress and will then succumb to severe stress. As their stress increases, progressively higher levels of cortisol are required. When the cortisol level cannot rise in response to stress, it is impossible to maintain the body in optimum stress response. In this respect,  we can conclude that stress does kill.

http://meeting.chestjournal.org/cgi/content/abstract/132/4/555
Chest 2007, Critical Care Sepsis: Markers. Wednesday, October 24, 2007
SALIVARY CORTISOL IN CRITICAL CARE PATIENTS. Eduardo F. Sad et al.
CONCLUSION: We conclude that salivary cortisol, a broadly available method but still not routinely used, can be a better method to assess hypothalamic-pituitary-adrenal axis in critical care patients, in which serum total cortisol is greatly influenced by low levels of protein, a common complication of these patients.  CLINICAL IMPLICATIONS: Salivary cortisol can become a good , easy and confiable test for the diagnosis of adrenal insufficiency in critical care patients. It is still necessary to determine normal salivary cortisol levels in these patients to establish this criteria.

Adrenal Fatigue

(49) http://www.ncbi.nlm.nih.gov/pubmed/6316831
Salivary cortisol: a better measure of adrenal cortical function than serum cortisol.Vining RF, McGinley RA, Maksvytis JJ, Ho KY. Ann Clin Biochem. 1983 Nov;20 (Pt 6):329-35. "Salivary cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum cortisol."

(50) http://www.ncbi.nlm.nih.gov/pubmed/2828410
Salivary cortisol measurement: a practical approach to assess pituitary-adrenal function. J Clin Endocrinol Metab. 1988 Feb;66(2):343-8. Laudat MH, Cerdas S, Fournier C, Guiban D, Guilhaume B, Luton JP.

(51) http://www.ncbi.nlm.nih.gov/pubmed/11164057
Salivary cortisol patterns in vital exhaustion. Nicolson NA, van Diest R. J Psychosom Res. 2000 Nov;49(5):335-42.

(52) http://bjp.rcpsych.org/cgi/content/full/184/2/136
Salivary cortisol response to awakening in chronic fatigue syndrome.Roberts AD, Wessely S, Chalder T, Papadopoulos A, Cleare AJ. Br J Psychiatry. 2004 Feb;184:136-41. (FULL TEXT)

(53) http://jcem.endojournals.org/cgi/content/full/86/8/3545
Hypothalamo-Pituitary-Adrenal Axis Dysfunction in Chronic Fatigue Syndrome, and the Effects of Low-Dose Hydrocortisone Therapy. The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 8 3545-3554 A. J. Cleare, J. Miell, E. Heap, S. Sookdeo, L. Young, G. S. Malhi and V. O’Keane (FULL TEXT) "In conclusion, this study provides evidence that there may be impaired adrenal cortical function in CFS on some measures and that low-dose hydrocortisone therapy is associated with a reversal of this HPA axis dysfunction."

(54) http://www.annalsnyas.org/cgi/content/abstract/1057/1/466
Stress-Induced Hypocortisolemia Diagnosed as Psychiatric Disorders Responsive to Hydrocortisone Replacement, SUZIE E. SCHUDER Ann. N.Y. Acad. Sci. 1057: 466–478 (2005).  "By correcting underlying hormonal insufficiencies, many patients improved, with some patients having a total reversal of psychiatric symptoms."

(55) http://edrv.endojournals.org/cgi/content/full/24/2/236
The Neuroendocrinology of Chronic Fatigue Syndrome. Anthony J. Cleare. Endocrine Reviews 24 (2): 236-252, 2003, Full Text.

(56) http://www.adrenalfatigue.org/
The official web site for the book, Adrenal Fatigue by James L Wilson D.C., N.D., Ph.D. The 21st Century Syndrome.

(57) http://www.cocoonnutrition.org/catalog/page_adrenal_cortical.php
The Use Of Adrenal Cortical Extracts In Adrenal Fatigue By James L. Wilson DC, ND, PhD

(58) http://crobm.iadrjournals.org/cgi/content/full/13/2/197
THE DIAGNOSTIC APPLICATIONS OF SALIVA— A REVIEW, The Monitoring of Hormone Levels, Eliaz Kaufman,Ira B. Lamster. Crit Rev Oral Biol Med 13(2):197-212 (2002)

(59) http://www.biodia.com/TechnicalCharts/SALIVARY_REFERENCES.pdf
Listing of about one hundred medical references on salivary hormone testing with hyperlinks.

(60) http://coastherbal.com/web_standard/adrenal_stress.html 
Adrenal Stress: Measuring and Treating, by  Thomas G. Guilliams Ph.D. The Standard, Volume 3, No. 1. Excellent review article on diagnosis, treatment of adrenal fatigue with salivary cortisol testing.

(61) http://www.amazon.com/review/R1QNDLO1R9EX3U/ref=cm_cr_rdp_perm
Adrenal Fatigue by James L Wilson D.C., N.D., Ph.D. The 21st Century Syndrome reviewed by Jeffrey Dach MD.

(62) http://www.amazon.com/review/R2IPB7XGMO20NE/ref=cm_cr_rdp_perm
Safe Uses of Cortisol (Cortisone, Hydrocortisone) by William McK., M.D. Jefferies (Author) reviewed by Jeffrey Dach MD.

http://jcem.endojournals.org/cgi/content/abstract/93/3/703
The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 3 703-709
Attenuated Morning Salivary Cortisol Concentrations in a Population-Based Study of Persons with Chronic Fatigue Syndrome and Well Controls
Urs M. Nater, Elizabeth Maloney, Roumiana S. Boneva, B

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