These presentation and medical conditions are not usually severe enough to be considered a medical emergency2.In medical practice or conventional medicine, this”concept of low adrenal functions “refers to the classical Addison’s Disease (AD), which is failure of adrenal functions and this is the mentioned specific condition is to be considered as a medical emergency.2  While the other spectrum of disease of over production of adrenal hormones known as Cushing’s Syndrome also considered as medical illnesses of worrying, however in between presentation of these clinical spectrum are often not recognized.

The idea and concern focus on this clinical spectrum that are often not recognized especially in busy primary care clinics, triggered this study to really look and showed that this clinical spectrum do exist in modern world and really impose health issues if neglected. Moreover, to revealed the association of this condition with the most common presentations or symptoms of these patients presented and its underlying medical conditions or chronic diseases like chronic allergy illnesses, bronchial asthma and arthritis.

Since Adrenal Fatigue has a broad spectrum of symptoms, many of these seem non specific and often labelled as psychological in nature origin like anxiety or depression. Most of time patients seeking many other medical specialities, undergone many investigations and yet are told that these symptoms are “nothingthat some rest won’t cure.”In other words, when extensive and lengthy medical workups fail to detect the cause of fatigue and lethargy, these symptoms are often dismissed as psychogenic in origin. However, we have now found out that they can actually to be facing to a condition called Adrenal Fatigue which of advanced stages can be incapacitating. This population at risks were studied and analysed in terms of demographic background, their hormones blood levels and their most common presenting complaints and their underlying medical illnesses were included.


Adrenal fatigue (AF) is also known as adrenal exhaustion a collection of signs and symptoms which resulted when adrenal glands functions behaves below the necessary level.2 When adrenal glands become exhausted and reduced its functions this condition creates a damaging effects for hormones in body. AF is not readily identifiable as an entity like any medical diseases such as measles or growth on the end of finger as people with AF often look and still able to act relatively normal.2 As their condition worsens, this low adrenal functions lays the foundation for other seemingly unrelated conditions such as frequent respiratory infections, allergies, rhinitis, asthma, frequent cold and a number of the health problems such as chronic fatigue syndrome, fibromyalgia, anxiety and even depression.2 However, in medical practise, the extreme low end of hypoadrenia known as Addison ‘s Disease is well recognised. Addison disease is the form of primary adrenocortical insufficiency; rare diseases affecting four in every 100,000 people with women being common in women than men.9There are actually two types of adrenal insufficiency which is primary and secondary. The former is known primary adrenal failure (mostly due to autoimmune adrenalitis)9,1011,12, or the secondary  caused by hypothalamic-pituitary impairment of the corticotropic axis (predominantly due to any pituitary disease). However this disease as mentioned as life threatening condition often overlooked, as the main clinical manifestations of adrenal insufficiency are non specific such as fatigue, anorexia and weight loss, therefore its diagnosis is often delayed affecting quality of life10,12.Back in 1855, AD was first described by Thomas Addison who is an English physician and scientist, as a clinical syndrome characterised by wasting and hyper pigmentation and identified its cause as a destruction of adrenal glands was by tuberculousadrenalitis, the most prevalent in the developing world9.  Currently, despite this so called breakthrough 150 years on there are still many challenges and advances with respect to the management of individuals with adrenal insufficiency9.


Adrenal gland being an important stress gland,  located on top of a kidney (“ad” “renal” means “over” the “kidneys”) and its only a size of a smaller than a walnut and its weighing less than a grape.2 These glands are secreting almost 50 different hormones, including steroid hormones such as adrenalin, cortisol, aldosterone, estrogen and testosteronethat are absolutely essential to our health and vitality to maintain homestasis.13 Cortisol, a glucocorticoid hormone is produced from a layer called zona fasciculate in the outer part of adrenal cortex and its daily production in young healthy women is 15-25 mg per day and about 25-35 mg in man to able to maintain optimal health and homeostasis.13,14 Cortisol is released in circadian rhythm,secretion is higher in the morning 30 minutes after awakening and awakening is a trigger of the HPA axis, and lowest at night.13 This rhythm demonstrates healthy adaptation to stress and is the only hormone in the body that increase with age and cortisol increases during stressful episodes, then it comes down after the episode, eventually with continuous stressor multiple stressful episodes will start to deplete the adrenals. The main functions of cortisol are fluid balance control, blood sugar regulation especially help insulin release for blood sugar maintenances, regulation of blood pressure, involves immune functions and inflammatory response.14 Therefore with reduction of adrenal functions, every organ and system are affected and often alteration of biochemical, cellular compensation leading to AFS.

Importantly, adrenal glands keep our body’s reactions to stress in balance as  anti-inflammatory and anti-oxidant of  cortisol able to minimise negative and allergic reactions, example are swelling and inflammation, environmental allergens, alcohol, drugs, certain  foods, cancer, infection, and autoimmune disorders (like rheumatoid arthritis or lupus syndrome).9,13,14,15 Cortisol also in details affect the utilisation of carbohydrates and fats, the conversion of fats and proteins into energy, the distribution of stored fat (especially around face and around our waist.), normal blood sugar regulation (hypoglycaemia is one of the health problems associated to poor adrenal function and one of the hallmark of AFS is irregular blood sugar patterns with hypoglycemia), and proper cardiovascular and gastrointestinal function.9,13,14,15

Moreover adrenal extremely important after mid-life of women (menopause age), as glands gradually become the major source of the sex hormones. These hormones have a whole host of physical, emotional and psychological effects, from the level of our sex drive to the tendency for gaining weight. Even our propensity to develop certain kinds of diseases and our ability to respond to chronic illness is influenced significantly by the adrenal glands. The more chronic the illness, the more critical the adrenal response becomes.


Interestingly, AF is categorized in mainly three stages. Stage 1 known as Alarm Reaction, Stage 2 is Resistance Response and Stage 3 as Adrenal Exhaustion16. For better understanding of AF any doctors should be aware of these stages of AFS in order helping doctors to diagnose AF early and able to manage our patients expectantly.

Stage 1: Alarm Reaction (Flight or Fight response). In this stage, the body is alarmed by the stressors and mounts an aggressive anti-stress response like cortisol to overcome the stressors and reduce stress levels. Fatigue is usually quite mild and usually occurs in the morning upon awakening or in the mid-afternoon. Symptoms are short lived and no physical or physiological dysfunction is clinically noticeable. Normal daily function continues unaffected, though peak performance cannot be achieved. Serum cortisol and adrenalin are high and DHEA level starts lowering.16

Stage 2: Resistance Response. With increasing chronicity and severity of stress, the adrenals are eventually unable to keep up with the body’s demand for cortisol Patients feel unrested, anxious and irritable. Other signs and symptoms are insomnia, recurrent infections, PMS, menstrual irregularities and symptoms of hypothyroidism as thyroid glands are usually affected at this stage. However, normal daily activities can still be carried out, but the sense of fatigue is pronounced at the end of each day as the body needs more rest than usual to recover despite a full night’s rest. At this point, pregnenolone steal (also called cortisol shunt sets in. Cortisol production becomes the predominant pathway of hormones production as the body favors the productions of these hormones. Total Pregnenolone, DHEA, testosterone and estrogen are getting low.The many warning signs of the body continue to be ignored, as most people will rely on more and more stimulants to keep their mood up especially multiple cups of coffee to sustain people and yet still puzzle with diagnosis as conventional medical work up being done seems revealed normal findings after many visit physicians for the first time.16

Stage 3: Adrenal Exhaustion.Adrenal Exhaustion refers to Stage 3 of Adrenal Fatigue.By time as adrenal function is weakened and deteriorating, our body’s need for adrenal hormones remains unabated if stress is ongoing and persistence. This process may takes over a few years as adrenals are no longer able to keep up with the ever-increasing demand for cortisol production needed to overcome the stress and they become exhausted. Cortisol and DHEAs output starts to decline and this usually happens gradually and symptoms are now persistent. If the stressors are severe, an adrenal crash may occur, to be followed by a longer than usual recovery. Despite rising ACTH, the adrenals are no longer able to keep up with the body s increased demand for cortisol production. Ovarian adrenal thyroid (OAT) axis imbalance occurs in female and adrenals-thyroid axis imbalance in men.16


Currently, there is no internationally accepted diagnosis of adrenal fatigue syndrome as it’s not clearly stated in main stream of medicine. However based on anti aging medicine, this condition is accepted by history taking toward ones energy pattern as this condition has classical energy pattern and salivary cortisol level test or serum blood test of morning cortisol and DHEA level1.


The main obstacles and challenges in diagnosing  AF are the main presenting complaints are non specific and symptoms usually precede signs which usually precedes syndromes  and not a single laboratory tests would definite confirm its diagnosis at which stages of AF. I have not found any previous studies done to determine what are the important presenting symptoms of adrenal fatigue or other forms of sublinical- hypoadrenia or this form of Non -Addisonianshyproadrenia in Malaysia even in other countries. Mainly many journals and scientific papers would discuss on the classical and extreme forms of Adrenal Insufficiency either primary or secondary causes.

However, there is one particular randomized controlled study titled ‘ Is Adrenal Exhaustion Synonym Of Syndrome Burnout at Workplace’? By NurkaPranjic, Sabrina Nuhbegovic, SanjaBrekalo and Azra in in Bosnia and Herzegovina were published in 2010. The main objective of the study is the assessment of the association of burnout syndrome with adrenal exhaustion specific symptoms and signs among 116 patients who were exposed to violence or mobbing at workplace and who were treated during 2005-2008 in Department of Occupational Pathology and Toxicology Tuzla; to detect symptoms and signs of adrenal exhaustion differences between patients who were exposed to act of violence as acute catastrophic event and patients who were long-term exposed to mobbing or chronic distress at workplace. Interestingly, the conclusion is when workers constant expose to repeat mobbing behaviour or have perception of extended distress reaction after act of violence at workplace they are suffering of Syndrome burnout and clinical picture of adrenal fatigue. They concluded also that in their opinion, there are no differences between following synonyms: adrenal exhaustion, emotional and somatic exhaustion, fatigue, adrenal fatigue or burnout syndrome in cases of long term exposure to stress at workplace or exposure to crisis situation-high level of stress at workplace. Despite their limitation of findings (generalitability) as symptoms and signs of adrenal fatigue without measuring level of cortisol, in fact adrenal exhaustion is an underlying factor in all illnesses.

Interestingly to note as well, according to Dr Duncan Carmichael from Cape Town, whom had given a wonderful series of lectures on Anti Aging Medicine in our University(UCSI), Malaysia, Dr Duncan stated that  ‘adrenal stress is a common problem as 6 out of 10 with hormonal imbalances have documented adrenal strain’ (2008 audit, TAAC, Cape Town, South Africa).

Adrenal fatigue syndrome is an important and common in our modern world, yet often being unrecognized due to its subtle signs and symptoms, presented in many stages of AFS and no reliable laboratory test. Most laboratory tests are designed to look for ‘disease’ states in human body and adrenal fatigues as we know are not a disease per se. In addition, there has never been reliable urine or blood tests that able to confirm and can definitely diagnose, mild forms of hypoadrenia. Although it is possible to use several standards blood and urine tests to really look for indications of this form of hypoadrenia, the interpretation is inexact and the normal range for adrenal functions on standard blood and urine tests includes everything but the most severe cases of adrenal malfunctions such as Addison’s Disease (the most extreme low) and Cushing syndrome (the most extremely high ). Further complicating issues that steroid hormones occur in more than one form in the body as cortisol can be in free, loosely bound and bound to blood protein forms. Free circulating hormones represent a meagre 1% of total amount of hormones available compared to bound hormones which act as reserve and become free hormones if needed.


Currently with the global recession looming, we are living in stressful times and high stress demand in modern life is full of challenges: overwhelming stress from the workplace, relationships, social isolation and loneliness for others. A recent survey carried out in 2004 in the EU (European Union) found that 90% of the respondents felt that stress in their respective countries is a major cause of illness.8  According to American experts from the Mayo Foundation for Medical Education and Research (MFMER)

“Persistent or chronic stress has the potential to put individuals at a substantially increased risk of depression, anxiety and many other emotional difficulties”.

According to NurkaPranjic et al, 2010 a survey done in 86 respondents who were exposed to chronic stress (being constant exposed to mobbing behaviour at work place more than 1 year) suffered all symptoms associated with adrenal exhaustion (range from 45 to 95%).

Stress increases inflammatory cytokines resulting in chronic inflammation, an important underlying factor in modern diseases like cardiovascular diseases(CVD), diabetes, respiratory illneses, mental disorders, auto-immunes diseases and cancers which has increased dramtically over the last three decades. The increasing rates of these chronic systemic illnesses suggest that this chronic inflammation, caused by excessive and inappropriate innate immune system (IIS) activity, is unable to respond appropriately to danger signals that are new in the context of evolution. This leads to unresolved or chronic inflammatory activation in the body.

Adrenal fatigue syndrome is an important and common in our modern world, yet often being unrecognized due to its subtle signs and symptoms, presented in many stages of AFS and no reliable laboratory test. Most laboratory tests are designed to look for ‘disease’ states in human body and adrenal fatigues as we know are not a disease per se.

In summary, the subtle between normal adrenal functions and adrenal fatigue syndrome are ignored, as many doctors do not look for it, do not properly diagnose subsequently do not treat correctly, moreover are AFS really present in  previously undiagnosed patients and if true its presence coexist we may face difficulties diagnosing as one isolated condition. However by looking and diagnosing this spectrum of illnesses serve as important tools in managing their outcome of illness they presented and deserve a better quality of life.


1. N.Pranjic, Sabina N, Sanja BL, et al. Association between adrenal Exhaustion and Burnout. Coll.Antropol. 2012; 3: 911-919.

2. Wilson JL PhD. Adrenal Fatigue: The 21st Century Stress Syndrome.Smart Publication, Petaluma (CA). 2001;  209.

3..Charmandari E, Tsigos C, Chrousos G, et al. Endocrinology of the stress response. Annu.Rev. Physiol. 2005; 67:259–284.

4. Goldstein DS. Catecholamines and stress.Endocr.Regul.2003 ; 37:69–80.

5. Michael H. Antoni, Susan K. Lutgendorf, Steven W. Cole, et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Natl. Rev. 2006; 6:240–248.

6. Flint MS, Baum A, Chambers WH, et al. Induction of DNA damage, alteration of DNA repair and transcriptional activation by stress hormones. Psychoneuroendocrinology. 2007;  32:470–479.

9. WiebkeArlt, BronoAllolio. Adrenal insufficiency.Lancet Vol 361.2003; 361:1881-93.

10. Betterle C, Dal Pra C, Mantero F, et al. Autoimmune adrenal insufficient and autoimmune polyendocrinesyndrome:Autuantibodies,autoantigens and their applicability in diagnose and disease prediction. Endocr Rev. 2002; 23:327-64.

11. Manson AS, Meade TW, Lee JA, et al. Epidermiological and clinical picture of Addison’s disease. Lancet 1968 ;2: 744-47.

12. Neufeld M, Maclaren NK, Blizzard RM, et al. Two Types of autoimmune Addisons associated with different polyglandular autoimmune (PGA) syndrome. Medicine (Baltimore).1981; 60:355.

13. Kirschbaum C, Hellhammer DH, et al. Salivary cortisol in psychoneuroendrocrine research: recent developments and applications. Psychoneuroendocrinology.1994 ; 19:313-33.

14. Dr TherryHertoghe, MD .The Hormones Handbook (the keys to safe hormones therapies: How to do it and how to solve therapy problems.)

15.Gozansky WS, Lynn JS, Laudenslager ML, et al. Cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-putuitary-adrenal axis activity.Clin endocrinol.2005; 63(3):336-41.

16. Micheal Lam, Dorrine Lam. Adrenal Fatigue Syndrome: Reclaim Your Energy and Vitality with Clinically Proven Natural Programs.

Prepared by:



IHS Certified in Advance Hormone Therapy

Certified Nutrigenomic Practitioner, Australia.

Msc. Anti Aging, Regenerative Medicine & Medical Aesthetics(UCSI)

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