HPA axis - Thyroid, Adrenal, Pituitary, Hypothalmus glands dysfunction tests (Found in high percentage of ME cases)


Scientific and Medical Evidence
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Listing of Research conducted worldwide section :
Abnormal adrenal glands & Abnormal HPA axis (Hypothalmus Pituary Adrenal axis)
Genetic markers
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Scientific Findings in Primer for International Consensus Criteria (2012)

This section includes various endocrine tests. It also includes tests recommended by Dr. Austin Darragh, Dr. Edward Conley, Dr. Sarah Myhill, Dr. Teitelbaum and other medical doctors who have treated many CFS patients. These can be carried out in hospitals or clinics or state / private laboratories.

The following factors will affect the biological markers - does the person have ME or some other similar illness ? what phase is the patient in, how long does he/she have the illness ? is the patient in remission or having a relapse ? does the patient have a co-morbid or co-existing illness with ME ? what infections does the patient have and where are they located ? is the patient severely ill, moderately ill or mildly ill ? the patient's genetic weaknesses ? was it gradual onset ME or rapid onset ?

1. Specific Tests and Biomarkers mentioned in ME Primer for Healthcare Professionals: based on Myalgic encephalomyelitis: International Consensus Criteria, 2012

The following paper may provide some additional guidance
Diagnosis and treatment of hypothalamic - pituitary - adrenal (HPA) axis dysfunction in patients with chronic fatigue syndro me (CFS) and fibromyalgia (FM). Holtorf K.. J Chronic Fatigue Syndr ( 2008 ) 14 : 59 - 88.

 

2. Hypopituitarism, post-traumatic Hypopituitarism (PTHP), and Pituitary Diseases often undiagnosed for years and also misdiagnosed as ME / CFS. How doctors are failing to spot the brain injury that could be behind 30,000 cases of 'chronic fatigue' Daily Mail, 17 May 2014. The Glucagon stimulation test is recommended by endocrinologists.


3. Thyroid Tests

Abnormal thyroid function is common in most CFS patients. Unfortunately low thyroid function is not picked up in most blood tests and this abnormality remains un-diagnosed in nearly all cases of CFS. Abnormal thyroid function creates multiple health problems for such patients.

- Thyroid subsets

  • Hashimoto's thyroiditis - often undiagnosed for years and also misdiagnosed as ME / CFS
  • Reverse T3 levels and activity, this is the most important biomarker in ME . Also check TSH, TPO (TPO - if positive, T4 & T3 dosage will need to be increased). T4 - free and bound, T3 - free (often low even if T4 is normal in ME due to the sick thyroid syndrome). (Dr. Austin Darrah).
    Genova Laboratory http://www.gdx.net/uk/product/20
  • Level of thyroid hormone bound to thyroid binding globulin (TBG). (Dr. Edward Conley).
  • Levels of Free T4 and Free T3 (Dr. Edward Conley).
  • TRH test. The best thyroid test of all.
  • Test for defects in the conversion rate of T4 to T3 (Dr. Edward Conley).
  • Test for Thyroiditis and inflammation of the thyroid gland (Dr. Edward Conley).



  • "25% developed varying autosoma l antibodies of which, for instance, antithyroid antibodies were found in 20% of cases studied."
    Myalgic Encephalomyelitis: Guidelines for Doctors John Richardson. Journal: J of Chronic Fatigue Syndrome, Vol. 10(1) 2002, pp. 65-80.
  • Anti-neuronal antibody Test
  • Dr. Sarah Myhill, Wales, UK (CFS expert) recommends the following: "I routinely check T4 in all my CFS patients. If the level falls in the lowest 20% of the so called "normal" range then I would treat with thyroxine. I often find GPs complaining that the best test of thyroid failure is a TSH - thyroid stimulating hormone. However this is often normal even with a low T4. I suspect this reflects the hypothalamic-pituitary-adrenal hypofunction in CFS."
    Dr. Sarah Myhill www.drmyhill.co.uk
  • Impaired thyroid function detected by special TRH tests. Also test for Hyperthyroid or Hypothyroid. (Dr. Austin Darrah)
  • Test thyroid antibody levels
  • Dr. Byron Hyde recommends the following - Checking the Pituitary-thyroid axis: "Changes in serum TSH, FT3, FT4, Microsomal Ab., PTH, calcium and phosphorous rarely occur until several years after illness onset. This anomaly can best be followed by serial ultrasounds of the thyroid gland, where a steady shrinking of the thyroid gland may occur in some M.E. patients with or without the development of non-serum positive Hashimoto's thyroiditis (a seeming contradiction in terms) and a significant increase in thyroid malignancy. In cases of thyroid wasting, serum positive changes tend to occur only after years and often not until the thyroid gland shrinks from the normal 13 to 21 cc. volume in an average adult female and 15-23 cc. volume in male patients to below a volume of 6 cc. (Mayo Clinic averages) (Rumack, Carol). The normal serum analysis of patients for thyroid dysfunction, TSH, FT4, microsomal antibodies etc., the golden rule of most physicians and endocrinologists, is simply not an adequate means of ascertaining thyroid" Dr. Byron Hyde, Diagnostic Tests
  • Check levels of phenylalanine and tyrosine. These are amino acids which are essential for normal thyroid function. Studies by Dr. Edward Conley at this clinic in Michigan show that over 80% of CFS patients are low in these two amino acids.
  • Get a thyroid scan for composition and function, and uptake of iodine (Dr. Edward Conley).
  • Oxytocin has multiple effects on the human body and hormones. Check Oxytocin levels.
  • For serious cases, get MRI / CAT / PET scans for the thyroid gland showing structure and functional analysis.
  • Thyroid Malignancy Test
    Thyroid malignancy risk is greatly increased in ME patients. Thyroid cancer exists in only 1 per 100,000 of the general public, yet 6000 per 100,000 in M.E. and CFS patients.
  • Dr. Martin Feldman, New York city, USA and Dr. Raphael Kellman are two of the leading doctors in the field of thyroid gland and adrenal gland diagnosis and treatments.

Test Laboratories

We will include links to other reputable tests and testing laboratories in the coming year

4. Adrenal Function Tests

Test for adrenal exhausation, this involves specialised adrenal tests. Also test for adrenal function and performance. Most ME patients have adrenal exhaustion and dysfunction.

  • Cortisol is usually abnormally low and DHEA is usually increased in ME.
  • The Buspirone, Corticol/Prolactin test. (Dr. John Richardson)
  • Abnormal Cortisol Production. As described in paper ' Alterations in Diurnal Salivary Cortisol Rhythm in a Population-Based Sample of Cases With Chronic Fatigue Syndrome Urs M. Nater et al. Psychosomatic Medicine April 2008 vol. 70 no. 3 298-305 '
  • Hormonal alterations in adolescent ME/CFS
    • Plasma ADH was significantly decreased
    • Increased serum osmolality and plasma renin activity
      Wyller VB, Evang JA, Godang K, Solhjell KK, Bollerslev J. Hormonal alterations in adolescent chronic fatigue syndrome. Acta Paediatr. 2010 May;99(5):770-3. Epub 2010 Mar 1.
  • there is evidence of mild hypocortisolism, blunted ACTH responses and enhanced negative glucocorticoid feedback in a portion of patients with ME/CFS
  • To distinguish between failure due to hypothalamic or pituitary stimuli, a test using corticotrophin-releasing hormone (CRH) is useful. P atients with hypothalamic failure do respond, whereas those with pituitary failure do not. (Dr. John Richardson)
  • Aeron LifeCycles Saliva Assay. Aeron LifeCycles Clinical Laboratory, USA. Tests levels of DHEA, Cortisol, estrogen, progesterone, testosterone. http://www.aeron.com
  • Adrenal Stress Profile test - Genova Laboratory  http://www.gdx.net/uk/
  • DHEA (saliva) - Genova Laboratory  http://www.gdx.net/uk/ DHEA levels are usually increased in ME.
  • DHEA Challenge Test - Diagnos-Tech, USA. http://www.diagnostechs.com . DHEA levels are usually increased in ME.
  • 24 hour urine analysis before and after administration of ACTH
  • Adrenal Stress Index Saliva Test - Diagnos-Tech, USA. http://www.diagnostechs.com
  • Several adrenal gland tests - Specialty Labs in Santa Monica, CA. USA http://www.specialtylabs.com
  • 8am PL. Cortisol, 24 Urinary free cortisol (often raised), 8am PL. DHEA level - diagnostic of ME if low would require supplementation by 25-50mg per day (Dr. Austin Darrah)
  • For all cases of ME , get MRI / CAT / PET scans for the adrenal gland showing structure and functional analysis. Some ME patients have shrunken adrenal glands according to some scientific research papers and clinical findings by doctors.
  • Oxytocin has multiple effects on the human body and hormones. Check Oxytocin levels.
  • Test for ACTH auto-antibodies. Wheatland R . Chronic ACTH autoantibodies are a significant pathological factor in the disruption of the hypothalamic-pituitary-adrenal axis in chronic fatigue syndrome, anorexia nervosa and major depression. Med Hypotheses. 2005;65(2):287-95. PMID: 15885924

 

5. Abnormal Genes and Genetic Pathways
Dr. Gordon Broderick's research team have uncovered several abnormal gene pathways which have direct effects on immune system function, HPA axis function, neurological function and metabolic function. These can differentiate healthy people from those with ME/CFS and also can differentiate ME/CFS from GWS patients.

1. Suppression of alanine and aspartate metabolism (kegg)
2. Starch and Glucose metabolism (kegg) - increased
3. Glycolysis / Gluconeogenesis (kegg) - increased
4. Phenylalanine metabolism (kegg) - decreased
5. Pentose Phosphate pathway (kegg) - increased
6. Trk (Tyrosine Kinase) receptor signalling mediated by pi3K and plc-gamma (nci/nature) - decreased
7. Disengagement of growth factor signalling and tissue repair ; aurora A signalling decreased.
Source: Presentation of scientific research findings of Dr. Gordon Broderick
Prefential Pathway Activation in Gulf War Veterans with Unexplained Neuroendocrine Immune Imbalances. G. Broderick et al. (2011)


5-HT transporter gene polyphormism in CFS patients
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Indication of endocrine abnormality induced by dysfunction of 5-HT system in CFS. Dysfunction in 5-HT system in the animal models. Reduced binding potential of 5-HTT in CFS patients
Neuroscience of Fatigue and CFS/ME by Using PET Molecular Imaging and Functional Neuroimaging
- Yasuyoshi Watanabe, Masaski Tanaka, Kei Mizuno, Akira Ishii, Emi Yamano, Sanae Fukuda, Yasuhito Nakatomi, Kouzi Yamaguti, and Hirohiko Kuratsune. IACFS/ME Conference. Translating Science into Clinical Care. March 20-23, 2014 • San Francisco, California, USA
- Association between serotonin transporter gene polymorphism and chronic fatigue syndrome Masaaki Narita, Naoko Nishigami, Naoko Narita, Kouzi Yamaguti, Nobuo Okado, Yasuyoshi Watanabe, Hirohiko Kuratsune. Biochemical and Biophysical Research Communications Volume 311, Issue 2, 14 November 2003, Pages 264–266

 

6. Specific Hormone Markers

Upregulation of Leptin in ME patients (Findings of Hornig et al., September 2013)

Higher levels of α-MSH in peripheral blood
"CFS patients with a disease duration of = 5 years had significantly higher levels of a-MSH in their peripheral blood. a-MSH could be a potent biological marker for the diagnosis of CFS, at least during the first 5 years after onset of the disease. "
The increase of alpha-melanocyte-stimulating hormone in the plasma of chronic fatigue syndrome patients Nobue Shishioh-Ikejima, Tokiko Ogawa, Kouzi Yamaguti, Yasuyoshi Watanabe, Hirohiko Kuratsune, and Hiroshi Kiyama. BMC Neurol. 2010; 10: 73.

 

7. Hypothlamus Test

  • Level of Hypothalmic hormones. ADH and Oxytocin are abnormally low in most ME patients.
  • The Buspirone, Corticol/Prolactin test (Dr. John Richardson)
  • To distinguish between failure due to hypothalamic or pituitary stimuli, a test using corticotrophin-releasing hormone (CRH) is useful. P atients with hypothalamic failure do respond, whereas those with pituitary failure do not. (Dr. John Richardson)
  • Test Vasopressin levels. Usually low in ME and FM patients.
  • Oxytocin has multiple effects on the human body and hormones. Check Oxytocin levels
  • For serious cases, get MRI / CAT / PET scans for the Hypothalmus gland showing structure and functional analysis. Test for damage caused by neuro-inflammation.

 

8. Pituitary Test

  • Dr. Byron Hyde recommends the following:
    • Pituitary-adrenal axis changes: this finding is infrequent.
    • Pituitary-ovarian axis changes:
    • Pituitary- (adrenal?)-Bladder dysfunction: occurs frequently in the
      early disease in some people. It is unknown if the cause is due to this
      link

  • Level of Pituitary hormones
  • Test Vasopressin levels. Usually low in ME and FM patients.
  • Oxytocin has multiple effects on the human body and hormones. Check Oxytocin levels.
  • For serious cases, get MRI / CAT / PET scans for the Pituitary gland showing structure and functional analysis. Test for damage caused by neuro-inflammation.

 

9. Pineal Gland

  • Test levels of Melatonin
  • For serious cases, get MRI / CAT / PET scans for the Pineal gland showing structure and functional analysis. Test for damage caused by neuro-inflammation.

 

10. Female hormones

  • Midcycle, FSH, LH, Oestradiol, Progesterone
  • Female hormone profile (Oestrogen, progesterone and testosterone levels in saliva) - Genova Laboratory http://www.gdx.net/uk/
  • Oxytocin has multiple effects on the human body and hormones. Check Oxytocin levels.

 

11. Male hormones

  • Testosterone (random). Genova Laboratory http://www.gdx.net/uk/
  • PSA (to eliminate prostrate hypertrophy / cancer). Genova Laboratory http://www.gdx.net/uk/
  • Oxytocin has multiple effects on the human body and hormones. Check Oxytocin levels.

 

12. Endocrine Other Tests

  • Check Aldosterone

  • Level of Pineal hormones

  • Level of Albumin levels