The lack of cortisol, the main glucocorticoid secreted by the adrenal cortex, manifests itself in symptoms that can vary greatly from one person to another. This feature accounts for much of the difficulty they experience in identifying the cause of their suffering, which is by the way, rarely understood by the majority of doctors.

Considering the involvement of this master hormone in basal metabolism, fatigue (that can become total exhaustion in advanced cases) and weight gain (which can switch to weight loss in severe cases) are common symptoms. The exact same symptoms can also be found in thyroid insufficiency, emphasizing the frequency of glandular weaknesses combining the thyroid and adrenal glands.

The cause of lack of energy can sometimes be traced; for example fatigue in the morning (impossibility to get up) is more thyroid, while fatigue at the end of the day is mainly adrenal. This latter form will get worse under stress irrespective of the time of day, which constitutes a classic aspect of lack of cortisol.

Other symptoms are found in both a lack of cortisol and thyroid hormone: difficulty to concentrate, the famous 'brain fog', poor memory, dizziness, and sometimes a compensatory over-agitation leading to confusion and poor efficiency.

Fortunately, deficiency of glucocorticoids often results in more specific symptoms that better guide the diagnosis. It is the case for hypoglycaemia (but in reality, this can also occur more frequently in hypothyroidism). This condition is most often characterised by a sudden malaise whereby the patient feels the need for sugary foods to feel better; a grave mistake as it will only feed the next crisis and of course will only further deplete glucocorticoid function…

Orthostatic hypotension constitutes another clear symptom directly implicated in cortisol insufficiency, along with evening palpitations, which worsen at bedtime, sometimes to the extent that they become true tachycardia. This should not be confused with palpitations occurring randomly, day or night, in hypothyroid patients whose hormonal treatment is poorly prescribed (excessive). Both types of palpitations can coexist in the same patient when adrenal insufficiency has not been recognised.

Clinical signs suggestive of low cortisol include cold and clammy skin (however cold extremities such as hands and feet, but also the nose, can be recognized in patients suffering from hypothyroidism), or hyperpigmentation of the skin, which is then an almost pathognomonic sign of glucocorticoid deficiency. These brown skin patches on the elbows or knees, darker lines on the palms of hands, and brownish stretch marks represent reliable signs of low cortisol. Finally another very useful means to establish a diagnosis is the abnormal tendency (for the subject in question) to tan more quickly, which unfortunately in this situation is not as good as one would hope!

Note also, in some patients, a tendency toward salty foods (but tending more towards sweet in response to hypoglycaemia), also a craving towards strong spices, or addiction to caffeine, tobacco and other stimulants. Each instinctively seeks to compensate for the lack of cortisol, a hormone that can be measured in blood, saliva, or - in the form of its various metabolites from liver detoxification – in 24-hour urine collection where they are known as the 17-hydroxysteroids family.

For more information, you are invited to visit my website www.gmouton.com where you will find a detailed Power Point presentation (202 slides in English) in the section Conferences/Functional Hormonology/ Adrenals. Enjoy reading!

Considering the frequency of adrenal deficiency, and having already discussed the symptoms and clinical signs, it would be useful to detail the various diagnostic tools at our disposal. We should be clear that we are talking here about moderate cases, and that Addison's disease, which is a major cortisol deficit, is not part of this discussion.

First, and most simply, cortisol can be measured in the blood. However we then depend upon a variable curve, known as the diurnal variations, which means levels follow the day/night cycle. Secretion of cortisol by the zona fasciculata of the adrenal cortex goes through a morning peak around sunrise, which is what wakes us (in conjunction with the fall of melatonin). This is followed by a slow decline over the day with a flattening of the curve towards bedtime, which is what helps us to fall asleep (with the help of the rise of melatonin).

We can see the difficulty of measuring cortisol in the blood, which is only taken at the beginning of the day. Such a blood test can only show an elevated peak, coming close to or exceeding the lab upper limit. Such a peak characterizes a pathologic stress and is usually followed by a subsequent collapse of the cortisol curve, reflected by severe fatigue mid-afternoon. Such an abnormal curve can lead to a small paradoxical rise at night, which will of course disturb restorative sleep.

It is for these reasons that the English favour salivary cortisol assays, with samples of cortisol taken throughout the day (upon rising-midday-around 5pm-bedtime) to obtain an insight into the cortisol curve. The reliability of salivary assays is disputed and only renowned laboratories with extensive experience in this field must be used. This test is often called the “Adrenal Stress Index” or ASI, which is of great interest for stress evaluation.

The cortisol curve is perfectly complementary to the testing of corresponding metabolites in a 24-hour urine collection. These are the various by-products of liver detoxification of cortisol. Their distribution is highly dependent on the genetic diversity of liver detoxification enzymes, the so-called genetic polymorphisms of the individual. Therefore their details don’t matter that much and we concentrate only on the result of the total metabolites grouped as 17-OH-steroids (or 17-hydroxy-steroids) in 24-hour urine, the markers of glucocorticoids.

This value truly reflects the glucocorticoid status of the patient as long as the collection of the 24-hour urine has been done correctly in line with the guidelines of the laboratory. It is, in fact, the integral curve of cortisol – this is the areas under the curve - and gives an overall idea of the secretion of cortisol throughout the 24-hour cycle. Only blood or salivary samples taken throughout the cycle results in a curve that allows us to better understand the cortisol fluctuations, but the 17-OH-steroids from urine can supply us with an overall view about a cortisol insufficiency which is the source of sadly misunderstood poor health.

For more information, you are invited to visit my website www.gmouton.com where you will find a detailed Power Point presentation (202 slides in English) in the section Conferences/Functional Hormonology/Adrenals. Very good reading!

We have now completed the study of the glucocorticoids secreted by the zona fasciculata of the adrenal glands, which covers everything there is to know about the cortisol family. Now we need to review the by-products of the zona reticularis (located closer to the adrenal cortex, between the zona fasciculata and medulla), the androgens.

As their name suggests, here we're talking about sex hormones or their precursors. This layer of the adrenal cortex has the capacity to secrete the full range of sex hormones (in both sexes, as each gender expresses a full set of hormones, although obviously in different ratios): oestrogens (17-beta-oestradiol and oestrone), progesterone and androgens (testosterone, androstenediol, androstenedione, and dehydroepiandrosterone or DHEA).

It is the latter, DHEA (measured in the blood in its sulphate form) that is of primary interest here because it constitutes by far the dominant androgen adrenal hormone. Measuring DHEA sulphate in the blood allows us to evaluate the whole activity of the zona reticularis at a glance. The levels vary between men (more) and women (less), by about 60%. DHEA has a ubiquitous role and can be transformed into all sex hormones according to individual needs.

Androgen function can also be evaluated more comprehensively through analysis of 24-hour urine collection, thus bypassing the fluctuations of the 24-hour circadian rhythm. The liver detoxification of the androgens can be measured in the same way as the metabolites of cortisol. The metabolites of DHEA are called urinary 17-ketosteroids. In this instance only the total number matters, not the detail of the by-products as this only reflects the diversity of hepatic genes.

The clinical picture of DHEA deficiency does not differ that much from that of cortisol. Common signs are fatigue, forgetfulness, poor sleep, and lowered immunity. Some symptoms are however more specific to low DHEA, even if they have nothing pathognomonic (meaning the same symptoms can be found in other diseases) such as muscular and joint pains, anxiety, depression, low libido (especially with women) and erectile dysfunction (in men, of course!).

Clinical signs may be more suggestive of a lack of DHEA: loss of hair (especially armpits and pubic) and blepharitis (inflammation of the edge of the eyelids which gives a characteristic redness). Additional signs are dry skin, dry and dull hair, dry and dull eyes, poor muscle tone, sometimes with weight gain around the waist … in short not a very good picture!

To close this series on the adrenal glands, a quick review of the products of the secretion of the outermost layer of the adrenal cortex, called the zona glomerulosa, should be done. They are the mineralocorticoids. Their main molecule is aldosterone but they also include, among others, 11-desoxycorticosterone.

When it comes to testing, there is an issue which originates from whether the patient is either standing or sitting, thus serum levels of aldosterone can be highly variable, whereas testing via 24-hour urine collection is more reliable by avoiding the large and constant blood fluctuations.

The dominant symptom of aldosterone deficiency is orthostatic hypotension (e.g. standing) but also by: low blood pressure, an obvious lack of concentration, and fatigue that becomes worse in the afternoon. The patient also has irresistible urges for salt, and, if drinking water, will need to go to the toilet rapidly and the urine output will be abnormally abundant and transparent.

We live in a world that is increasingly more polluted by thousands of chemical molecules called xenobiotics: insecticides, herbicides, various industrial waste, cosmetics, cleaning products, detergents, and additives…. Many xenobiotics have an anti-thyroid action: dioxins, Polychlorinated Biphenyls (PCBs), Polycyclic Aromatic Hydrocarbon (PAHs), organochlorine pesticides (including the infamous dichloro-diphenyl-trichloroethane (DDT), Polychlorinated Dibenzofurans, Brominated Flame Retardants (BFRs), Perfluorooctanoic Acid (PFOA), Perfluorooctanesulfonic Acid (PFOS) and the phthalates.

You will find all the scientific publications relevant to these major endocrine disruptors in the conference presentation “Thyroid Gland and Xenobiotics", a PDF that is free to download from my website www.gmouton.com (see the section “Conferences” and the heading “Functional Hormonology”). A simple glance at the structure of these chemicals (see specific slides) clearly shows the similarities with thyroid hormones, hence their propensity to interfere with them.

Dioxins have hit the headlines due to the contamination of Seveso in July 1976. They are the by-products of many industrial processes and can accidently contaminate eggs and poultry (Belgium 1999), dairy products (Netherlands 2004), and also meat (Ireland 2008). They have been the subject of a European program to reduce these emissions by 90% between 1985 and 2005. They continue to contaminate plants and animals due to their high chemical stability.

Polychlorinated Biphenyls (PCBs) have been industrially produced since the 1930’s (notably Monsanto), but since the 1980’s they have been banned as a result of their extreme toxicity. Their lipid solubility and their persistence in the environment (potentially centuries) help to explain the persistent contamination of animal milks (and also human milk!), as well as their accumulation in fish and seafood. While direct human exposure has shown a marked decrease, the enormous quantities of these pollutants continue to be a significant source of bioaccumulation in the fat of many land and sea organisms.

Polycyclic Aromatic Hydrocarbon (PAHs) are known to have carcinogenic properties, especially benzopyrene, generated by the incomplete combustion of organic materials exposed to high temperatures (petrol, diesel, coal, wood), from both industrial and domestic sources. Proximity to factories and the intensity of road traffic increases passive exposure. Cigarette smoking constitutes a deliberate exposure via tar and smoke; it illustrates their frightening toxicity.

Organochlorine pesticides are renown since the advent of DDT, the first modern insecticide, developed at the beginning of the Second World War. It accumulates in fish along with other aquatic species generally, as well as predators like birds of prey and humans. Held in 2001, the Stockholm Convention targeted its ban and has since been ratified by 158 countries. The Worldwide Health Organisation (WHO) has given its agreement for its utilization in certain countries in order to eradicate malaria; however it has announced its intent to eliminate their use by 2020.

Polychlorinated dibenzofurans (furans) accumulate in the fatty parts of food of animal origin (meat, fish). Being very stable soluble compounds they have significantly accumulated in the food chain. They chemically resemble dioxins and result largely from waste incineration, including medical waste.

The brominated flame-retardants (BFRs) are intended to reduce the flammability of plastic polymers. There are more than 75 chemicals additives of this type, with extremely diverse molecular structures. The Tetrabromobisphenol A (TBBPA) inhibits the binding of the active thyroid hormone T3 on to the thyroid hormone receptors. The deleterious effects of this fearsome endocrine disruptor are vividly demonstrated by its inhibition of the metamorphosis from tadpole to frog (see 'Article of the Month' from 02/2013).

The incredible adventure of the tadpoles as indicators of chemical pollution is told in the article of the month for February 2013 on the website www.gmouton.com; click on “Articles” then “10 – Article of the Month”. You will discover the best way to locate infinitesimal quantities of xenobiotics in water. Because they block the receptors for the active T3 thyroid hormones this is a more sensitive, more reliable, less expensive means to identify them.

The aim here is not to find an ingenious way to evaluate the cleanliness of the water but to demonstrate the disastrous role played by this long list of pollutants to our thyroid function.

Three substances remain to be talked about: PFOA, PFOS and phthalates.

Perfluorooctanoic Acid (PFOA) has been synthesized by industry since the 1940’s as a surfactant to stabilize emulsions. PFOA is extremely stable and persists indefinitely in the environment by insidiously polluting water and food. You can review thyroid dysfunctions linked to PFOA by checking the conference "Thyroid & Xenobiotics” on my website site (see the “Conferences/Functional Hormonology section). Furthermore, this xenobiotic reduces fertility and causes birth defects, promotes some cancers and can even contribute to the development of cardiovascular disease.

Perfluorooctane sulfonic acid (PFOS) belongs to the family of perfluorinated compounds. It is a man-made chemical of global concern and is now found in the environment as well as in living organisms. The voluntary cessation of its production in 2002, for reasons of serious toxicity (including thyroid), has not prevented its detection over the surface of the globe, even in Canada, a country that has never produced any and even in the supposedly virgin land of the Canadian Arctic.

Phthalates have been manufactured industrially as plasticizers since the 1950’s. They are widely used to make plastics more flexible. Transparent, with practically no colour or odour, they have been used extensively in cosmetics to improve skin penetration of active ingredients. Nearly all products made from polyvinyl chloride (PVC) contain some phthalates, which means all food packaging and toys. Phthalates migrate very easily from plastic wrappers that cover fatty food like meat or cheese. Their danger and toxicity been increasingly recognized, their ban is spreading in Europe but unfortunately not yet in Asia. They exert anti-thyroid actions in pregnant women, as well as in men, according to American studies: see the corresponding slides. These endocrine disruptors also affect all aspects of human reproduction: reduced fertility, foetal mortality, foetal malformations, reduced foetal body weight….

Therefore it is not surprising to encounter more and more cases of thyroid insufficiency today’s! Chemical aggressors are plentiful, mainly because many current chemical compounds have two cycles of 6 carbon atoms typical of our thyroid hormones. This results in complex interference with the production of thyroid hormones and their attachment to the corresponding receptors. Since the widespread use of pesticides and herbicides, we face a real chemical warfare against thyroid function in humans and animals.

This situation keeps has only worsened since the development of the plastics industry and we can certainly say that the surge of brominated flame-retardants will potentially constitute the final blow to our desperate thyroid glands. To resist this chemical assault you must have a grade A thyroid function! In addition, we must underline the extent of which these endocrine disruptors mess up human health: let’s cite also bisphenol A which has a multitude of toxic effects and whose omnipresence in plastics (released by heating) contributes to the global obesity epidemic.