Function of Adrenal Glands

The adrenals are triangular shaped glands, located on top of both kidneys; they produce hormones which regulate the body’s response to stress, and also some sex hormones and their precursors.

They are divided into an inner part – the medulla- where adrenaline and noradrenaline are produced as an immediate reaction to acute stress; and an outer layer- the cortex- the site of production of cortisol, which is crucial to the body’s defence against chronic or repeated stress. The cortex is also the site of production of another major hormone, aldosterone, which controls salt and water balance, and is a major factor in the regulation of blood pressure. Also produced in the adrenal cortex are DHEA and adrenal sex hormone precursors such as pregnenalone and androstendione- which function as antioxidants and balance the negative effects of cortisol, as well as acting as an auxiliary site of sex hormone synthesis.

The production of adrenal hormones is, in turn, regulated by a feedback loop, involving the pituitary and hypothalamus in the brain; which regulate the production of adrenal stress hormones through the action of ACTH (Adrenal Corticotrophin Hormone) on the adrenal glands. This system is referred to as the HPA axis (hypothalamic-pituitary-adrenal axis).

Disorders of the adrenal glands

Essentially, disorders of the adrenal glands can be divided into syndromes resulting from the excessive production of cortisol – Cushing’s Syndrome- (associated with obesity, diabetes and other complications); Addison’s syndrome- (a life-threatening adrenal insufficiency affecting the body’s ability to fight infection, respond to stress and maintain normal blood pressure- requiring lifelong treatment with cortisol); tumours producing excessive amounts of adrenaline and noradrenaline e.g. phaeochromocytoma- (presents with surges in blood pressure); and defective  enzymatic pathways resulting in excessive production of certain sex steroids ( resulting in virilisation of female foetuses, or development of abnormal body hair- hirsuitism).

Additionally, exposure to prolonged or repeated stressors can drain the adrenal glands’ reserve, leading to a constellation of symptoms termed Adrenal Fatigue.

Stress & The General Adaptation Response

Acute Stress & the “Fight or Flight” response

shutterstock_79070602Primitive human beings evolved with the ability to respond to threats to their safety by Fight or Flight. This was a very appropriate response if the threat was the attack of a wild animal or a warring member of another tribe; the mere recognition of danger triggered a release of hormones from the adrenal glands- initially adrenaline and noradrenaline – whose function was to ensure adequate delivery of  oxygen and glucose to fuel the muscles involved in fighting or fleeing the assailant.

This was accomplished by speeding up the heart and respiratory rate, increasing the amount of blood pumped out at each stroke by the heart muscle, increasing blood flow to the brain  by elevating the blood pressure; dilating the pupils so we could see better; diverting  blood flow from the peripheries (feet and hands) and from the digestive organs towards the skeletal muscles, and preparing our bodies for injury/bleeding by decreasing blood flow to the skin, putting our blood clotting mechanism in high gear, and secreting endorphins ( natural pain-killing substances produced by the brain in response to injury or exercise).

Cortisol would then be released from the adrenal cortex, if the threat was not immediately dealt with- the purpose being to elevate blood sugar and mobilize additional glucose from reserves of fatty tissue, to fuel a prolonged struggle. Cortisol was also needed to suppress inflammation in wounds or damaged tissue.

All of this is a very appropriate response to a short-lived physical threat, but our bodies do not differentiate between different types of stressors- ie the exact same response happens if we have an argument with the boss, we run late for a meeting, we have trouble paying our bills,  we are worried about a family member who is sick, we are recovering from surgery,  an acute illness or cancer treatments, or we feel inadequate in a social situation, a new job, or poorly prepared for an exam…the common factor being the perception of adverse consequences or a threat to our “status quo”.

In other words- Perceived Stress is Stress.

Stressors are also cumulative… i.e. the effects of repeated fight or flight responses add up, as we encounter multiple stressors in our daily lives, we start to suffer adverse reactions to excessive outpouring of adrenal hormones. These could range from anxiety, insomnia and palpitations  from too frequent surges of adrenaline; tension headaches, muscle aches and pains from repeated tensing of skeletal muscles; cold hands and feet from shutdown of peripheral blood flow; indigestion and bloating from diversion of blood flow from the digestive tract… all the way to chronic elevation of blood pressure and blood sugar, deposition of fat around the abdomen, thinning of bones and impaired ability to fight infection from chronically elevated cortisol.

Cortisol, while it damps down the inflammatory response to wounds, thus preventing further tissue injury and speeding up healing in the acute phase- is a catabolic hormone- i.e. it breaks down tissue – including muscle, skin, bone and brain tissue (chronic stress and depression result in shrinkage of the hippocampus, an important part of the brain for short-term memory), and high levels of cortisol will also result in impaired immune function by suppression of lymphocytes– i.e. we get more infections and are slower to recover from infections or illness, and  our ability to recognise and  fight off cancer cells is affected.

Chronic stress eventually depletes our reserves of cortisol, with   further derangement of the   immune system, resulting in allergies, multiple chemical sensitivities, and autoimmune disorders (all symptoms of a heightened inflammatory state).

General Adaptation Syndrome

Hans Selye, a researcher into the  biological effects of stress, identified common patterns of response to prolonged stress in laboratory animals, and  in 1936 coined the phrase General Adaptation Syndrome, to describe the stages they went through;

  • The first stage, Alarm, corresponded to the initial outpouring of adrenaline, noradrenaline, and cortisol in response to an acute stressor, which would last minutes to hours, associated with increased muscular strength, alertness, and energy necessary to deal with the threat.
  • This was followed by Recovery-  1-2 days of fatigue and depleted energy, while the animal was recovering from the initial expenditure of energy.
  • If the stressors were ongoing, this was then followed by a prolonged period called the Resistance phase, which could last months or years, while the adrenal reserves were adequate to respond to the ongoing demands. This was dependent on adequate secretion of cortisol and aldosterone to produce glucose from reserves of fat and protein, and keep the blood pressure elevated by means of salt and water retention. However, prolonged elevation of cortisol would result in impaired immune function, and typically in this phase animals were more prone to infections, and slower recovery from injury.
  • Eventually came the stage of Exhaustion, characterized in animals by haemorrhage into the adrenal glands, shrinkage of the thymus gland (gland associated with immune function) and general failure of various organ systems. In humans, this phase probably corresponds to an Addisonian crisis (extreme life threatening hypoadrenalism usually occurring in the presence of Addison’s disease or adrenal suppression caused by long term exogenous use of steroids)
Adrenal Fatigue: Signs & Symptoms

Three stages ; Alarm- Adrenaline rush; Resistance -Cortisol elevation;  Exhaustion Cortisol depletion…Symptoms of early and late Adrenal fatigue

Adrenal Fatigue occurs when exposure to chronic, repeated or severe stress depletes the reserves of the adrenal gland, resulting in characteristic symptoms..

  • Early adrenal fatigue can be experience as vigilance- a state of heightened arousal- due to surges in adrenaline and cortisol in response to various perceived stressors; this presents as anxiety, sweating, palpitations, insomnia, and cravings for sugary foods and energy boosters such as caffeine. It corresponds to the phase of resistance as described above- when the person is said to be “living off their adrenaline”, and may feel they are coping fine with the stress load. However, after a variable period of time – months or years- the continued drain on their adrenal reserves, leads to progression in symptoms, as described below.
  • Fatigue –particularly in the morning on waking; it may take several hours and a jolt of caffeine to reach an energy level compatible with carrying on normal function. Heat and humidity exacerbate the fatigue, as does exercise, and the fatigue progresses so that ordinary routine tasks eventually seem more onerous. Energy often picks up mid morning, or after a snack, but takes a dive in mid afternoon; energy may again pick up  a bit in the early evening; and in the early stages  of adrenal fatigue, a person may feel agitated at bedtime – “tired but wired”
  • Mood – irritable, depressed; loss of enjoyment of hobbies and pastimes- everything, including socializing, seems to be too much bother. Major reduction in sex drive.
  • Decreased productivity, less able to multitask, foggy thinking; defective short-term memory, poor concentration, difficulty grasping abstract concepts or learning new skills; can’t cope; burnout.
  • Hypoglycaemia– fatigue and other symptoms improve temporarily with refined carbohydrates; (to be followed by a further dive in energy a hour and a half to 2 hours later, due to stimulation of insulin secretion); craving for salty foods (reflects deficiency of aldosterone which controls salt & water balance). A craving for fast foods– fat and protein- is explained by the body’s need to convert these alternate sources of  energy into glucose needed for cellular metabolism-a process called  gluconeogenesis which is under the control of cortisol, the stress hormone.
  • Weight gain, with a change in body composition to reflect abdominal fat deposition, and  wasting of skeletal muscles– so called apple shaped weight gain; a combined effect of cortisol, which elevates blood sugar by breaking down muscle,  and the secondary elevation in  insulin levels, which tries to lower blood sugar storing it in fat cells. This is self- perpetuating; as  a decrease in the patient’s muscle mass results in a lower basal metabolic rate,; which, unless the person does more exercise, leads to further weight gain
  • Dizziness on standing up ( reflects decreased aldosterone secretion and its effect on salt & water balance and the maintenance of normal blood pressure)
  • Increased susceptibility to infections; much slower recovering from illnesses, especially respiratory illness, or surgery (elevation of  cortisol suppresses white  blood cell activity)
  • Heightened sensitivity to allergens: multiple chemical sensitivities, presence of autoimmune disorders : this reflects late stage adrenal fatigue with depletion of cortisol, which is needed to supress excessive inflammatory activity , and resulting derangement of immune function
  • Joint and muscle aches and pains a proinflammatory symptom of advanced adrenal fatigue

*Diagnosis of adrenal fatigue

*Note: There are many other causes of chronic fatigue:- A thorough medical assessment is needed to rule out infections, cancer, neurological disorders, autoimmune conditions, anaemia, severe hypothyroidism and other aetiologies

A diagnosis of adrenal fatigue is usually made in the setting of a history of multiple stressful events/ prolonged illness /trauma or surgery; the presence of symptoms as above; the exclusion of any of the other major causes of fatigue; plus certain patterns of cortisol on salivary testing. Additionally certain physical signs may be present –

  • A drop in blood pressure on standing
  • Inability to sustain pupillary constriction on shining of a light from the side of the eye….normally bright light will cause pupillary constriction by means of the sympathetic nervous system,; in certain cases of adrenal fatigue, the constriction may be present initially, but after a short time, while the light is still shining, the pupil will begin to dilate.

Salivary hormone testing:

Normal secretion of cortisol follows a characteristic pattern, known as a circadian rhythm, which mirrors the sleep-wake cycle; it peaks around 6-7am, falls off by about a third by noon, reaching its lowest point by mid afternoon; thereafter there is usually a slight rise towards the early part of the evening. We usually do four-point testing-around 7am 12 noon 3pm, 10pm to look at the diurnal pattern

Salivary testing is ideal- it sidesteps the inconvenience of going back to the lab for multiple blood tests, and is less stressful than having blood drawn –(the stress of having a blood test is by itself enough to  cause a temporary elevation in serum cortisol).

In the early stages of adrenal fatigue, we may see a rise in cortisol either on waking, or in the early part of the evening- this corresponds to the resistance phase. As the adrenals become depleted, we tend to see a flat curve. An early clue to the diagnosis is a steep fall-off between the first and second values- a drop of 60% between the morning and noon levels is characteristic.

We might also look at the Cortisol: DHEA Ratio; as we get older, DHEA production tends to fall, reflecting physiological aging; whereas cortisol may rise slightly. At age 20 we would expect  a ratio of 0.6; by 45 typical value of 1; by 60, the ratio will average 1.5; and by the mid-seventies, the ratio will exceed 2:… so a high ratio in a young person reflects adrenal dysfunction- whereas a lower ratio in an older person is more indicative of adrenal fatigue.

DHEA and Cortisol have opposing metabolic effects- Cortisol tends to elevate blood sugar and increase insulin resistance- DHEA lowers or normalises blood sugar and improves sensitivity to insulin. Increased insulin resistance is a precursor to diabetes.

Treatment of Adrenal Fatigue

Treatment starts with understanding why we are susceptible to adrenal fatigue. Aside from serious or recurrent physical illness (especially recurrent respiratory infections) trauma or surgery- the major causes are psychological stressors: eg financial difficulties, work related problems, relationship issues – death or illness of a loved one, separation or divorce; even “good” events such as moving house, starting a new job ,having a new baby, beginning university studies- will add to our stress load, as they involve a change in the status quo. You may be asked to complete a Life Events Inventory, which assigns a score to different potentially stressful life events occurring over the preceding year: the cumulative score is a good indicator of propensity to illness, including adrenal fatigue

·         Lifestyle Modification

The first step in the treatment of adrenal fatigue involves attention to healthy eating habits, moderate exercise, getting sufficient sleep, and stress management Sleep is important for the restorative body functions- certain hormones such as melatonin and growth hormone are only secreted in association with the sleep cycle. These hormones are necessary for cell repair, and proper immune function (see section on Cortisol-Melatonin balance)

Stress Management

We offer a comprehensive approach to stress management- through individual counselling, group sessions or corporate seminars.

Our focus encompasses both relaxation training –ie yogic breathing techniques, progressive muscle relaxation visualization, autohypnosis, meditation  and autogenic training – designed to tone down the sympathetic nervous system arousal that accompanies the vigilance phase of adrenal fatigue – and cognitive restructuring – which helps us to reframe our perceptions of the stressful event and develop better coping strategies.

Patients that would benefit from relaxation training are those experiencing symptoms such as insomnia, palpitations, headaches, overwhelming anxiety, panic attacks, agoraphobia; even those experiencing difficulty with concentration, or feeling overwhelmed with tasks.

Cognitive restructuring helps us examine our perceptions beliefs and attitudes towards stress. Sometimes that involves identifying negative patterns of thoughts; dealing with negative behavioural patterns such as procrastination or chronic lateness; learning more effective time management and boundary setting strategies, and dealing with interpersonal conflict. We also examine the hardiness factors- ie traits that promote resilience towards stress

Nutritional Support

Prolonged stress raises the inflammatory status of the body, leading to production of more free radicals; thus it is important to supplement with antioxidants, such as Vit C and Vit E ( avoid in smokers); Omega 3 fatty acids will also help decrease inflammation)  Vit B complex, particularly Niacin, Pantothenic acid, Vit B6  B12 are required to maintain proper cellular metabolism, as are trace elements such as Magnesium, Iodine, Chromium , Zinc, Selenium, Manganese, Molybdenum, Copper. (Hair analysis can be used to check for deficiencies of trace minerals- see Nutritional& Metabolic medicine)

Patients may also benefit from a slight increase in salt intake , as aldosterone depletion leads to salt and water imbalances, and increasing dietary fibre intake and supplementing with probiotics and digestive enzymes may help to counteract sluggish bowels. Due to derangements in immune function, some patients may develop food sensitivities, with accompanying symptoms such as bloating, rashes and even cognitive clouding and depression – and may benefit from allergy testing (See section on Nutritional and Metabolic medicine.)

Adaptogenic Herbs

The following herbs will support adrenal function:

  • Licorice root increases energy, endurance and vitality, decreases symptoms of hypoglycaemia, improves wound healing and has anti-inflammatory effects. A potential side effect is slight elevation of blood pressure- but this rarely an issue unless there is hypertension to start with , or the person consumes large quantities of the herb..
  • Ashwagandha as an adaptogenic herb, it tends to normalize levels of cortisol- ie reduce high levels and increase low levels. It has anti-inflammatory effects and will help reduce joint & muscle aches and pains
  • Siberian Ginseng supports adrenal function, normalizes metabolism and reduces symptoms of fatigue, and increases energy levels.Its neurotransmitter effects are beneficial for lethargy, anxiety and insomnia (NB Korean Ginseng is a different herb, which may be beneficial for men – stimulating energy, and libido; but it  may cause acne and hirsuitism in women)
  • Ginger Root is adaptogenic, (ie normalizes adrenal function) stimulates the metabolism (helps burn off fat) decreases nausea, and aids digestion
  • Gingko Bilbao is an antioxidant which stimulates cognitive function  mood and energy levels. It has the potential to interact with blood thinners such as Warfarin
  • Rhodiola – derived from Chrysanthemum stimulates cognitive function, helping to offset symptoms such as brain fog, memory deficits etc

Adrenal Cellular Extracts

Were first widely studied during the Spanish Flu pandemic of 1918 which caused 10 million deaths worldwide A study of autopsy findings revealed significant effects on the adrenal glands in its victims- either massive enlargement of the glands or haemorrhages into the glands- (compare with the results of Hans Selye’s studies of the end stages of adrenal exhaustion on laboratory animals)

Administration of adrenal cellular extracts to a study group of several hundred people resulted in more rapid recovery, with significant reduction in the serious sequelae of the disease. Adrenal cell extracts were widely used in the 30s, 40s , until the development of synthetic cortisol, which had much more dramatic effects on the recovery from serious infections (More powerful synthetic steroids are commonly used today to speed recovery from respiratory infections and acute inflammatory states such as acute allergic reactions, asthma attacks, autoimmune disorders: but it is common knowledge that protracted use of synthetic steroids , or short-term use of high-dose synthetic steroids, has an inhibitory effect on the adrenals which can last for 6 months, or even longer)

Adrenal cortical  cellular extracts are not hormones, but are the contents of adrenal cortex cells – ie nucleic acids, enzymes, and nutrients that are used to support adrenal cell function, and when used in conjunction with lifestyle modification , herbs, and nutritional supplements, will accelerate recovery from adrenal fatigue

Bioidentical Hormonal Replacement

Hormonal replacement for adrenal fatigue can include adrenal precursor hormones  such as pregnenalone or progesterone (the path for steroid hormone synthesis starts with cholesterol, which is converted into pregnenalone, and a couple of steps later, progesterone.- Both adrenal cortex hormones and sex hormones arise from these precursor hormones), DHEA, or bioidentical cortisol can also be used

(Cortisol is rarely used, except in cases of extreme adrenal fatigue, and then in divided doses not exceeding 10-20 mgs per day to mimic physiological secretion.. The concern with administering higher doses, long-term cortisol- or the administering the  much more potent synthetic hormones, prednisone or prednisolone- – is that they can cause long term suppression of adrenal function – ie “switch off” adrenal hormone secretion by means of a feedback loop via the HPA axis. Also there are potential side effects such as bone loss, hypertension, elevated blood sugars and insulin resistance,, changes in body composition, ,decreased resistance to infections etc – that come with prolonged administration of exogenous steroids.)

DHEA can improve energy, drive, libido; normalize blood sugar, and promote lean muscle mass- but caution is needed to avoid excessively high doses in females , where too high levels can lead to oily skin, acne and hirsuitism.


Can be protracted despite the above measures; mild cases of adrenal fatigue can take 6-9 months for significant symptom resolution, while severe adrenal fatigue can take up to 2 years of adaptogenic herbs, adrenal cellular extracts, hormonal replacement, and permanent lifestyle modification. It is worth noting that, in the setting of adrenal fatigue, sub-optimal response will be seen with sex hormone replacement, thyroid replacement therapy etc even if there are demonstrable deficiencies in these hormones

Suggested reading: An excellent and easily read explanation of adrenal fatigue, its diagnosis and treatment, can be found in the book

Adrenal Fatigue the 21st Century Stress Syndrome by Dr James L Wilson