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News - Adrenals - A student's guide - Part I

By Holly Taylor BSc(Hons) DipCNM MBANT NTCC

The adrenal glands are a pair of triangular-shaped endocrine glands that sit like little hats on the top of the kidneys. Each gland is separated into two distinct hormone-producing structures; the adrenal medulla on the inside and the adrenal cortex on the outer surface. 

The adrenal medulla

The adrenal medulla is at the core of the adrenal gland. It develops from nervous tissue in the embryo and is part of the sympathetic division of the autonomic nervous system. Rather than releasing neurotransmitters across a synapse, the cells in the adrenal medulla secrete hormones directly into the bloodstream. In stressful situations, and during exercise, impulses from the hypothalamus stimulate the sympathetic neurons in the medulla, initiating the secretion of the catecholamine hormones adrenaline and noradrenaline. Derived from the amino acid tyrosine, these water-soluble hormones are the major biochemicals underlying the fight-or-flight response. They bind to adrenergic receptors in the plasma membrane of many cell types and bring about changes that are aimed at preparing the body for an emergency. These include:

  • Increasing the cardiac output – to improve flow of oxygenated blood to the brain, heart and muscles.
  • Raising blood pressure – to protect against hypovolaemic shock if any blood loss occurs.
  • Redirecting blood away from the skin and digestive organs to the skeletal muscles, coronary arteries, liver and brain – to prioritise those organs needed for emergency action.
  • Increasing the metabolic rate and raising the blood sugar – to provide fuel for combat or escape.
  • Dilating the airways – to provide more oxygen to fuel cellular respiration.
  • Dilating the pupils – to let in more light and improve vision.
  • Reducing the clotting time of the blood – to reduce the risk of bleeding to death, should an injury occur.
  • Increasing ACTH secretion from the anterior lobe of the pituitary – to initiate back-up stress responses. 

The adrenal cortex

 The adrenal cortex is devoted to the synthesis of steroid hormones from cholesterol. It is divided into three different zones, each of which secretes distinct hormones.

Zona glomerulosa

This is the outer layer, responsible for the production of mineralocorticoids, the most of important of which is aldosterone. Aldosterone works with the kidneys to control the levels of sodium and potassium in the body. It has a direct influence on internal fluid balance, as well as on blood pressure. Aldosterone also promotes the excretion of H+ in the urine, which helps to prevent acidosis.

Zona fasciculata

Situated between the glomerulosa and reticularis, the zona fasciculata is the middle layer of the cortex, responsible for producing glucocorticoids, such as cortisol. These hormones are essential to life and work in many ways to regulate metabolism and provide resistance to stresses such as exercise, fasting, fright, temperature extremes, high altitude, blood loss, infection, surgery, trauma and disease. Their actions include:

  • Initiating the breakdown of protein, mainly from muscle fibres, to liberate amino acids into the bloodstream to be used for energy production.
  • Stimulating the release of fatty acids from adipose tissue, ready to be used as an energy source.
  • Stimulating liver cells to perform gluconeogenesis – the manufacture of glucose from other molecules, such as fats and amino acids.
  • Sensitising blood vessels to the hormones that cause vasoconstriction, to increase blood pressure and guard against shock.
  • Acting as powerful immune suppressants, tempering inflammatory, allergic and autoimmune reactions.
  • Influencing mood and behaviour.

Zona reticularis

This is the inner layer of the adrenal cortex, responsible for the manufacture of DHEA and sex hormones. DHEA is the most abundant adrenal steroid in the body. Through its peripheral conversion to androgens and oestrogens, it helps regulate a wide range of metabolic and endocrine functions, from fat catabolism to energy production. It is important for balancing the body’s stress response and guarding against the degenerative conditions associated with ageing.

Control of adrenal secretions

Secretion of adrenal cortical hormones is regulated by a complex interaction between the hypothalamus, pituitary and adrenal glands. These three glands work together through a negative feedback mechanism, referred to as the HPA axis, which adjusts cortisol levels, in response to the needs of the body.

When the level of cortisol in the bloodstream drops too low, or when a stressor is perceived, the hypothalamus determines how much cortisol is needed and starts to release corticotropin-releasing hormone (CRH). CRH then signals to the pituitary to release a set amount of adrenocorticotropin-releasing hormone (ACTH), which travels in the bloodstream to the adrenal cortex and activates hormone production in each of the three zones.

Although each zone makes different hormones, the process always begins with the ACTH initiating the release of cholesterol within the cells. The cholesterol is then used to manufacture pregnenolone, the precursor of all steroid hormones. No matter what hormone is being made, pregnenolone is formed first and is then converted into the required steroid, via a series of enzymatic reactions.

Under conditions of prolonged or severe stress, the majority of pregnenolone is directed down the stress hormone pathways, leaving very little left to be turned into the other steroid hormones. This situation is sometimes referred to as a ‘pregnenolone steal’ and is one of the reasons that long-term stress can cause hormone imbalances, low libido and a difficult menopause.

In the zona fasciculata, it takes less than a minute after the initial stimulation by ACTH for the pregnenolone to be converted into cortisol and released into circulation. Once in the bloodstream, cortisol is able to target a wide range of body cells, including those in the hypothalamus, allowing adrenal output to be monitored and altered on a minute-by-minute basis.

Adrenal dysfunction

From a medical perspective, only the extreme deviations from normal adrenal function are recognised (see Box 1). These include conditions of adrenal hypersecretion, such as phaeochromocytoma, primary aldosteronism and Cushing’s syndrome, as well as pathologies such as Addison’s disease, which result from severe adrenal cortex insufficiency. While serious adrenal diseases are relatively rare, patients suffering from varying degrees of adrenal dysfunction are fast becoming the bread and butter of CAM practitioners.

General adaptation syndrome

In order to appreciate the links between adrenal dysfunction and ill health, you first have to understand how the body adapts to stressful situations. In 1939, Hans Selye, former director of Experimental Medicine at the University of Montreal, performed an integrated analysis of the effects of stress on adrenal gland function. Based on his findings, he created a model for stress response called the General Adaptation Syndrome or GAS. According to Selye, there are three stages of stress response:

Alarm – acute stress

This is the initial fight-or-flight response to an acute stressor, mediated by the sympathetic nervous system. The stressor may be a psychological stress or any other insult on the body that taxes the adrenals, including things such as chronic infections, allergies, chemical toxins, use of stimulants, poor nutrition, physical trauma and poor sleep habits. Hormonally, there is a release of adrenaline and noradrenaline from the adrenal medulla, as well as a release of cortisol from the adrenal cortex. The alarm response is a short-term defence mechanism that prepares the body for a crisis. It is characterised by an increase in breathing rate, heart rate, blood pressure and blood sugar, as well as muscle tension, sweating and a diversion of blood away from the digestive system. The alarm phase is usually short-lived. Once it is over, the body goes through a recovery phase that lasts 24-48 hours. During this time, the levels of stress hormones plummet, leaving the person feeling tired and exhausted. If the stress is severe, some people may never recover from this phase, moving straight from alarm into exhaustion.

Box 1
Condition Common causes Major signs and symptoms Key laboratory findings

 Phaeochromocytoma

 Excess secretion of catecholamines as a result of: benign tumour of the adrenal medulla

High Blood pressure
Headaches
Sweating
Palpitations 

 

 High levels of adrenaline and noradrenaline

Primary aldosteronism Excess secretion of aldosterone as a result of: tumour of adrenal cortex Hypertension High levels of aldosterone. 
Low potassium and magnesium levels. 
Metabolic alkalosis
Cushing's syndrome Excess secretion of glucortoids as a result of: adrenal cortex tumour; oversecretion of ACTH by pituitary; secretion of ACTH by another kind of tumour, e.g. pulmonary, pancreatic; prolonged use of medical steroid therapies A rounded face
Central obesity
A fatty hump between the shoulders
Thin skin
Stretch marks
Weak bones
Fatigue and weakness
High blood pressure
High blood glucose
Increased thirst and urination
Irritability, anxiety or depression
High cortisol levels
Addison's disease Insufficient secretion of mineral and glucocortoids as a result of: autoimmune destruction of the adrenal cortex Severe fatigue and weakness
Loss of weight
Increased pigmentation of the skin
Faintness and low blood pressure
Hypoglycaemia
Nausea/vomiting
Salt cravings
Painful muscles and joints
Low cortisol and aldosterone levels
Low blood sodium, chloride and potassium

Resistance – chronic stress

Unfortunately, the nature of modern life means that, for many people, stressors are long-term or multiple. When this occurs, the body enters a second phase called resistance, which is mediated by the hormones cortisol and aldosterone. During this period, cortisol directs the conversion of fats, proteins and carbohydrates into glucose, to raise blood sugar levels, and aldosterone promotes the retention of water and sodium to keep the blood pressure up. Cortisol is also a powerful anti-inflammatory, which, in small amounts, can aid tissue repair. However, if the arousal continues long-term, cortisol output can become excessive, suppressing the immune system. A prolonged resistance reaction can result in weight gain and increased susceptibility to infections and chronic diseases such as diabetes, cancer and cardiovascular disease. Eventually, if this phase goes on for too long, the adrenals become so weak that they can no longer sustain a stress response and the body enters the exhaustion phase. The resistance phase can last anything from days to years, depending on the type of stressor or a person’s individual constitution.

Exhaustion

No matter how vital the person, chronic stress can, eventually, lead to adrenal exhaustion or ‘burn-out’. This period is characterised by deficient production of cortisol and aldosterone, sometimes with additional random pulses of adrenaline. The low levels of cortisol lead to rapid hypoglycaemia, while deficient aldosterone production results in excessive sodium secretion and a sudden drop in blood pressure. In the face of insufficient glucose and an electrolyte imbalance, cells cannot function properly and the body starts to become weak. What’s more, the immune-modulating effects of cortisol are lost, so people in the exhaustion phase become more prone to developing imbalances such as allergies and autoimmune conditions.

Adrenal fatigue

In humans, the exhaustion phase of stress presents itself as a sliding scale of increasing degrees of adrenal fatigue. In clinic, this may present as a stand-alone condition or as an underlying factor in a range of other complaints (see Box 2).

Common symptoms experienced by adrenal fatigue patients include: 

  • Poor sleep or insomnia
  • Difficulty getting up in the morning
  • Drowsiness during the day
  • Fatigue
  • Low or fluctuating mood
  • Emotional instability
  • Anger
  • Irritability
  • Food cravings, especially for sugar, salt or stimulants
  • Constant hunger
  • Alcohol and food intolerances
  • Rapid heartbeat
  • Headaches
  • Poor memory and concentration
  • Skin problems
  • Fat around the middle
  • Joint pains
  • Frequent colds/infections
  • Digestive difficulties
  • Menstrual difficulties/irregularities
  • Lowered sex drive 
Box 2
Conditions connected to adrenal fatigue 
Addictions
Allergies
Autoimmune disease
Digestive problems
Metabolic syndrome
Chronic fatigue syndrome
Chronic infections
Blood sugar imbalances
Fibromyalgia
Thyroid disorders
Herpes outbreaks
Mild depression
PMS and menopausal symptoms
Sleep disruptions

 

 

 

 

 

 

 

 

 

 

 

 

Testing adrenal function

People cope with stress in different ways, so, as practitioners, it’s important to be able to determine when stress is having a negative impact on clients’ health. Testing adrenal function can help to identify the stage of stress response and severity of adrenal dysfunction, as well as motivating clients by providing evidence of their state of health. Options for testing adrenal function include salivary hormone analysis, the Ragland blood pressure test and the pupillary response test.

Saliva testing

This test is a powerful, precise and non-invasive way of measuring adrenal stress hormone levels. Using saliva samples allows measurement of the amount of active stress hormones in the body. This is important as it reflects the levels of hormones that will be having an effect at a cellular level, rather than the total amount floating around in the bloodstream. Overall, the test gives a detailed picture of the adrenal hormone cycle, by measuring salivary cortisol and DHEA levels in saliva samples taken at four specific time points during the day. It can help to pinpoint the type and stage of stress your client is experiencing, making is easier to build an effective protocol.

Ragland test

This test compares blood pressure measurements while lying down and then again immediately on standing. When adrenal function is healthy, the adrenals help increase the blood pressure to compensate for gravity on standing, so the blood pressure rises. In adrenal fatigue, this mechanism is compromised and blood pressure often drops as the client stands.

Technique:

  1. Ask client to lie down and rest quietly for a few minutes
  2. Take their blood pressure and record the figures
  3. Ask client to stand and immediately re-take blood pressure

Ideally, the systolic blood pressure should rise 10-20mm/Hg on standing. If the blood pressure drops on standing, it indicates some form of hypoadrenia. The more severe the drop, the more pronounced the adrenal fatigue.

Note: Dehydration can also cause blood pressure to drop on standing, so make sure your clients are well hydrated before performing this test!

Pupillary response test

This technique can be used to determine the presence and severity of adrenal fatigue. Normally, when light hits the eye, the circular muscle around the iris contracts to shrink the size of the pupil. In states of adrenal fatigue, the pupil is unable to hold this contraction and begins to dilate despite light shining on it. This is because pupillary constriction is controlled by the sympathetic branch of the autonomic nervous system and is, therefore, highly influenced by hormonal cascade from the adrenal system.

Technique:

  1. Darken room and wait for about a minute so the client’s eyes can adjust to the darkness
  2. Instruct client to look at a fixed point without blinking
  3. Shine a penlight into the pupil from a distance of 20-30cm and at a 45º angle
  4. Observe the reaction of the pupil for 20 seconds or so.
Pupillary response test results
Result Interpretation                                                   
Pupil holds constriction for 20 seconds Good adrenal health
Pupil constricts but pulses after 10 seconds Fair adrenal health
Pupil pulses and gradually enlarges Mild adrenal fatigue
Pupil pulses and rapidly enlarges Adrenal fatigue
Pupil immediately becomes larger or fails to constrict Pronounced adrenal fatigue

 

Coming up in part II:

  • Protocol ideas for adrenal health – what you need to know about diet, exercise, sleep and stress management.
  • Nutraceutical support – your guide to supplements and herbs for managing adrenal dysfunction.
  • Working with non-responders – what to consider next for clients that are not recovering. 

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