Diseases and Environmental Toxins Suspected to Cause Them

Here is a link to a table of Diseases and Environmental Toxins Suspected to Cause Them.

Don

The Inadvertent and Continuous Exposure of Fetuses to Environmentally Active Chemicals

There is a third type of exposure that needs to be addressed: the inadvertent and continuous exposure of fetuses to environmentally active chemicals, such as dioxins and BPA.                 

Dioxins

Depending on the context (time of exposure, organ, presence or absence of estrogens) dioxins have either estrogenic or antiestrogenic effects. Despite cross-talk between the aryl hydrocarbon and ERs (139), the mechanisms underlying these opposite effects have yet to be elucidated. Rats exposed prenatally (gestational d 15) to TCDD and challenged with the chemical carcinogen DMBA at 50 d of age showed increased tumor incidence, increased number of tumors per animal, and shorter latency period than rats exposed prenatally to vehicle and to DMBA at 50 d of age. These TCDD-exposed animals had increased numbers of terminal end buds at puberty (140). Because these structures are believed to be the site where mammary cancer arises, these results were interpreted as evidence that TCDD increased the propensity to cancer by altering mammary gland morphogenesis. Interestingly, Fenton (31) showed that prenatal exposure to TCDD results in impaired development of terminal end buds that remain in the gland for prolonged periods, whereas in the normal animals terminal end buds are transient structures that regress when ductal development is completed.

BPA, a ubiquitous xenoestrogen

The ubiquitous use of BPA provides great potential for exposure of both the developing fetus, indirectly through maternal exposure, and the neonate, directly through ingestion of tinned food, infant formula, or maternal milk (11). Indeed, BPA has been measured in maternal and fetal plasma and placental tissue at birth in humans (141). A recently published study conducted by the Centers for Disease Control, the first using a reference human population, showed that 92.6% of over 2500 Americans had BPA in their urine (142). Measured urine concentrations were significantly higher in children and adolescents compared with adults. BPA has also been measured in the milk of lactating mothers. These data indicate that the developing human fetus and neonate are readily exposed to this chemical.

In rodents, BPA has been shown to readily cross the placenta (143, 144) and bind α-fetoprotein (the estrogen-binding protein that prevents maternal estrogen from entering the circulation of the fetus) with negligible affinity relative to estradiol; this results in enhanced bioavailability during neonatal development. BPA is present in the mouse fetus and amniotic fluid during maternal exposure in higher concentrations than that of maternal blood.

The U.S. EPA has established the safe daily intake of BPA to be 50 μg/kg body weight/d based on the assumption that the main source of exposure is oral through food ingestion. However, recent publications suggest that food is not the only relevant source of exposure and that the half-life of BPA in humans is longer than expected (6). Numerous publications addressing fetal exposures to BPA have used parenteral administration. This practice was based on one hand on the fact that the fetus is exposed to BPA through the internal milieu of the mother, and on the other hand that parenteral administration via an osmotic minipump allows for a precise and constant level of exposure. Using this route of administration, exposure of a pregnant mouse dam to 25 and 250 ng BPA/kg body weight/d (namely, 2000 and 200 times lower than the safe dose) for 14 d beginning on d 8 gestation has been shown to impact certain aspects of development in their female offspring. When examined on gestational d 18, fetuses of mothers exposed to the higher dose of BPA exhibited altered growth parameters of the mammary gland anlagen. Changes in the appearance of the mammary epithelium were observed, such as decreased cell size and delayed lumen formation, as well as increased ductal area. In the stroma, BPA exposure promoted advanced maturation of the fat pad and altered localization of fibrous collagen (128). Because maturation of the fat pad is the driving event for ductal growth and branching, it is likely that the increased ductal area in BPA-exposed animals is due to the accelerated formation of their fat pads. By postnatal d 10, in the offspring born to mothers exposed to either dose of BPA, the percentage of proliferating epithelial cells was significantly decreased relative to those not exposed. At 30 d of age, the area and number of terminal end buds relative to the gland ductal area increased, whereas cell death in these structures decreased in BPA-exposed offspring compared with controls. It is likely that the reduced cell death in the terminal end buds of BPA-exposed females may be the cause of the observed ductal growth delay because cell death is essential for both the hollowing and the outward growth of the subtending duct. Collectively, these effects observed at puberty may be attributed to an increased sensitivity to estradiol that has been observed in the BPA-exposed animals (145). Because of the new epidemiological data cited above and the effects found in the low-dose animal studies using parenteral exposure, the EPA recommendations need to be reevaluated.

In animals exposed perinatally to BPA, there was also a significant increase of ductal epithelial cells that were positive for progesterone receptor at puberty. These positive cells were localized in clusters, suggesting future branching points. Indeed, lateral branching was significantly enhanced at 4 months of age in offspring born to mothers exposed to 25 ng BPA/kg body weight/d (145). These results are compatible with the notion that increased sensitivity to estrogens drives the induction of progesterone receptors in epithelial cells, leading to an increase in lateral branching. By 6 months of age, perinatally exposed virgin mice exhibit mammary glands that resemble those of a pregnant mouse, as reflected by a significant increase in the percentage of ducts, terminal ends, terminal ducts, and alveolar buds (146). Additionally, intraductal hyperplasias, which are considered preneoplastic lesions, were observed starting at 3 months of age (147).

To explore the links between prenatal BPA exposure and mammary gland neoplasia, a rat model was chosen because it closely resembles the human disease regarding estrogen dependency and histopathology. BPA was administered to pregnant dams at doses of 2.5, 25, 250, and 1000 μg/kg body weight/d. Fetal exposure to BPA, from gestational d 9 to postnatal d 1, resulted in the development of carcinomas in situ in the mammary glands of 33% of the rats exposed to 250 μg/kg body weight/d, whereas none of the unexposed animals developed neoplasias (148). These cancers were only observed after the animals had reached young adult age. Fetal exposure to BPA significantly increased the number of precancerous lesions (intraductal proliferation) by three to four times, an effect also observed in puberty and during adult life. The lesions observed in the BPA-exposed animals were highly proliferative and contained abundant ER-positive cells, suggesting that the proliferative activity in these lesions may be estrogen mediated. Comparable preneoplastic lesions were found in a study using a different rat strain (149). Additionally, this study found stromal alterations such as desmoplasia and mast cell invasion; these features are often observed during neoplastic development. Moreover, when challenged with a subcarcinogenic dose of nitrosomethylurea, only the BPA-exposed animals developed palpable tumors (carcinomas). The period of vulnerability of the mammary gland to BPA does not cease at the neonatal stage. BPA exposure during lactation followed to exposure to the carcinogen DMBA resulted in mammary tumor multiplicity and reduced tumor latency compared with control animals (exposed solely to DMBA) (150). These results indicate that perinatal exposure to environmentally relevant doses of BPA results in persistent alterations in mammary gland morphogenesis, development of precancerous lesions, and carcinoma in situ. Moreover, the altered growth parameters noted in the developing mammary gland on embryonic d 18 suggest that the fetal gland is a direct target of BPA, and that these alterations cause the mammary gland phenotypes observed in perinatally exposed mice at puberty and adulthood.

In summary, exposure to estrogens throughout a woman’s life, including the period of intrauterine development, is a risk factor for the development of breast cancer. The increased incidence of breast cancer noted during the last 50 yr may have been caused, in part, by exposure of women to estrogen-mimicking chemicals that have been released into the environment from industrial and commercial sources. Epidemiological studies suggest that exposure to xenoestrogens such as DES during fetal development, to DDT around puberty, and to a mixture of xenoestrogens around menopause increases this risk. Animal studies show that exposure in utero to the xenoestrogen BPA increases this risk. Moreover, these animal studies suggest that estrogens act as morphogens and that excessive perinatal exposure results in structural and functional alterations that are further exacerbated by exposure to ovarian steroids at puberty and beyond. These altered structures include preneoplastic lesions, such as intraductal hyperplasias, and carcinomas in situ. Additionally, these mammary glands are more vulnerable than their normal counterparts to carcinogenic stimuli. Exposures to other endocrine disruptors that are not estrogenic, such as dioxins, were reported to increase breast cancer incidence in humans and to alter mammary gland development in animal models. Collectively, these data support the notion that endocrine disruptors alter mammary gland morphogenesis and that the resulting dysgenic gland becomes more prone to neoplastic development.

Source: http://edrv.endojournals.org/content/30/4/293.full

Don

Endocrine Disruptors - What are they?

The group of molecules identified as endocrine disruptors is highly heterogeneous and includes synthetic chemicals used as industrial solvents/lubricants and their byproducts [polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), dioxins], plastics [bisphenol A (BPA)], plasticizers (phthalates), pesticides [methoxychlor, chlorpyrifos, dichlorodiphenyltrichloroethane (DDT)], fungicides (vinclozolin), and pharmaceutical agents [diethylstilbestrol (DES)].                 

Natural chemicals found in human and animal food (e.g., phytoestrogens, including genistein and coumestrol) can also act as endocrine disruptors. These substances, whereas generally thought to have relatively low binding affinity to ERs, are widely consumed and are components of infant formula (1, 2). A recent study reported that urinary concentrations of the phytoestrogens genistein and daidzein were about 500-fold higher in infants fed soy formula compared with those fed cow’s milk formula (3). Therefore, the potential for endocrine disruption by phytoestrogens needs to be considered.

It is difficult to predict whether a compound may or may not exert endocrine-disrupting actions. Nevertheless, in very broad terms, EDCs such as dioxins, PCBs, PBBs, and pesticides often contain halogen group substitutions by chlorine and bromine. They often have a phenolic moiety that is thought to mimic natural steroid hormones and enable EDCs to interact with steroid hormone receptors as analogs or antagonists. Even heavy metals and metalloids may have estrogenic activity, suggesting that these compounds are EDCs as well as more generalized toxicants. Several classes of EDCs act as antiandrogens and as thyroid hormone receptor agonists or antagonists, and more recently, androgenic EDCs have been identified.

Exposure occurs through drinking contaminated water, breathing contaminated air, ingesting food, or contacting contaminated soil.

Source: http://edrv.endojournals.org/content/30/4/293.full

Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement

If this doesn't one thinking about what's going in their body or the need to do a purification program yearly read again!

Review: Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement (2009)

Abstract
There is growing interest in the possible health threat posed by endocrine-disrupting chemicals (EDCs), which are substances in our environment, food, and consumer products that interfere with hormone biosynthesis, metabolism, or action resulting in a deviation from normal homeostatic control or reproduction. In this first Scientific Statement of The Endocrine Society, we present the evidence that endocrine disruptors have effects on male and female reproduction, breast development and cancer, prostate cancer, neuroendocrinology, thyroid, metabolism and obesity, and cardiovascular endocrinology. Results from animal models, human clinical observations, and epidemiological studies converge to implicate EDCs as a significant concern to public health. The mechanisms of EDCs involve divergent pathways including (but not limited to) estrogenic, antiandrogenic, thyroid, peroxisome proliferator-activated receptor γ, retinoid, and actions through other nuclear receptors; steroidogenic enzymes; neurotransmitter receptors and systems; and many other pathways that are highly conserved in wildlife and humans, and which can be modeled in laboratory in vitro and in vivo models. Furthermore, EDCs represent a broad class of molecules such as organochlorinated pesticides and industrial chemicals, plastics and plasticizers, fuels, and many other chemicals that are present in the environment or are in widespread use. We make a number of recommendations to increase understanding of effects of EDCs, including enhancing increased basic and clinical research, invoking the precautionary principle, and advocating involvement of individual and scientific society stakeholders in communicating and implementing changes in public policy and awareness.

Outline of what is covered in the position statement:

I. General Introduction to Endocrine Disruption

• A. Important issues in endocrine disruption
• B. The role of endocrinologists in discerning effects of EDCs

II. Overview of Endocrine Disruption and Reproductive Health from a Clinical Perspective                                            

• A. Clinical aspects of endocrine disruption in humans
• B. Clinical dimorphism of EDCs on male and female reproduction
• C. Experimental and clinical evidence of EDCs and potential mechanisms

III. Clinical and Translational Impacts of EDCs on Female Reproduction                                            

• A. Introduction to female reproductive development and function
• B. Polycystic ovarian syndrome (PCOS)
• C. Premature ovarian failure, decreased ovarian reserve, aneuploidy, and granulosa steroidogenesis
• D. Reproductive tract anomalies
• E. Uterine leiomyomas
• F. Endometriosis

IV. Endocrine Disruptors, Mammary Gland Development, and Breast Cancer                                            

• A. Windows of vulnerability to carcinogenic agents and “natural” risk factors
• B. Theories of carcinogenesis
• C. Susceptibility of the breast during puberty and adulthood
• D. Susceptibility of the mammary gland during the perinatal period
• E. Perinatal exposure to environmentally relevant levels of endocrine disruptors

V. Male Reproductive and Developmental Health: The Human Evidence                                            

• A. Introduction to male reproductive health
• B. Male reproductive function and development
• C. Semen quality: temporal trends and EDC exposure
• D. Male urogenital tract malformations
• E. Testicular germ cell cancer
• F. Conclusions

VI. Prostate Cancer                                            

• A. Introduction to prostate cancer
• B. Evidence and mechanisms for EDC effects on the prostate

VII. Neuroendocrine Targets of EDCs                                            

• A. Endocrine disruption of reproductive neuroendocrine systems
• B. Hypothalamic-pituitary-adrenal (HPA) effects of EDCs
• C. Thyroid, metabolism, and growth
• D. Hormonal targets of neuroendocrine disruption

VIII. Thyroid Disruption                                            

• A. Introduction to thyroid systems
• B. Environmental chemicals impacting thyroid function
• C. Environmental chemicals impacting thyroid hormone transport, metabolism, and clearance
• D. Environmental chemicals impacting the thyroid hormone receptor

IX. Environmental Chemicals, Obesity, and Metabolism                                            

• A. Introduction to EDCs and the obesity epidemic
• B. Environmental estrogens and obesity
• C. Peroxisome proliferator-activated receptor (PPAR) γ and organotins
• D. Phytoestrogens
• E. Endocrine disruptors, diabetes, and glucose homeostasis
• F. Endocrine disruptors and cardiovascular systems
• G. Estrogenic EDCs and cardioprotection
• H. Advanced glycation end-products (AGEs)
• I. Conclusions

Don

The Ratio Between Index and Ring Finger

The ratio between index and ring finger is believed to be linked to exposure to the male hormone testosterone in the womb. On average, men tend to have longer ring fingers and women longer index fingers. The higher the testosterone, the greater the length of the ring finger and the more "masculine" the resulting child – whether male or female.

Why Men's Ring Fingers Are Longer Than Their Index Fingers: Male-Female Ring Finger Proportions Tied to Sex Hormones in Embryo

ScienceDaily (Sep. 6, 2011) — Biologists at the University of Florida have found a reason why men's ring fingers are generally longer than their index fingers -- and why the reverse usually holds true for women.

The finding could help medical professionals understand the origin of behavior and disease, which may be useful for customizing treatments or assessing risks in context with specific medical conditions.

Writing in the Proceedings of the National Academy of Sciences, developmental biologists Martin Cohn, Ph.D., and Zhengui Zheng, Ph.D., of the Howard Hughes Medical Institute and the department of molecular genetics and microbiology at the UF College of Medicine, show that male and female digit proportions are determined by the balance of sex hormones during early embryonic development. Differences in how these hormones activate receptors in males and females affect the growth of specific digits.

The discovery provides a genetic explanation for a raft of studies that link finger proportions with traits ranging from sperm counts, aggression, musical ability, sexual orientation and sports prowess, to health problems such as autism, depression, heart attack and breast cancer.

It has long been suspected that the digit ratio is influenced by sex hormones, but until now direct experimental evidence was lacking.

"The discovery that growth of the developing digits is controlled directly by androgen and estrogen receptor activity confirms that finger proportions are a lifelong signature of our early hormonal milieu," Cohn said. "In addition to understanding the basis of one of the more bizarre differences between the sexes, it's exciting to think that our fingers can tell us something about the signals that we were exposed to during a short period of our time in the womb. There is growing evidence that a number of adult diseases have fetal origins. With the new data, we've shown that that the digit ratio reflects one's prenatal androgen and estrogen activity, and that could have some explanatory power."

Cohn and Zheng, also members of the UF Genetics Institute, found that the developing digits of male and female mouse embryos are packed with receptors for sex hormones. By following the prenatal development of the limb buds of mice, which have a digit length ratio similar to humans, the scientists controlled the gene signaling effects of androgen -- also known as testosterone -- and estrogen.

Essentially, more androgen equated to a proportionally longer fourth digit. More estrogen resulted in a feminized appearance. The study uncovered how these hormonal signals govern the rate at which skeletal precursor cells divide, and showed that different finger bones have different levels of sensitivity to androgen and estrogen.

Since Roman times, people have associated the hand's fourth digit with the wearing of rings. In many cultures, a proportionally longer ring finger in men has been taken as a sign of fertility.
"I've been struggling to understand this trait since 1998," said John T. Manning, Ph.D., a professor at Swansea University in the United Kingdom, who was not involved in the current research. "When I read this study, I thought, thank goodness, we've attracted the attention of a developmental biologist with all the sophisticated techniques of molecular genetics and biology."

In dozens of papers and two books, including the seminal "Digit Ratio" in 2002, Manning has studied the meaning of the relative lengths of second and fourth digits in humans, known to scientists as the 2D:4D ratio.

"When Zheng and Cohn blocked testosterone receptors, they got a female digit ratio," Manning said. "When they added testosterone they got super male ratios, and when they added estrogen, super female ratios. And they've provided us with a list of 19 genes that are sensitive to prenatal testosterone and prenatal estrogen.

"I find this completely convincing and very useful," Manning said. "We can now be more focused in our examination of the links between digit ratio and sex-dependent behaviors, diseases of the immune system, cardiovascular disorders and a number of cancers."

Cohn, whose uses the tools of genetics, genomics and molecular biology to study limb development, said his lab began studying the digit ratios after Zheng became determined to find an explanation.
"He suggested that the 2D:4D ratio would be an interesting question, and I have to admit to being skeptical," Cohn said. "When he came back with the initial results, I was blown away. We looked at each others hands, then got busy planning the next experiment."

Finger Length Predicts Mental Toughness in Sport

ScienceDaily (Dec. 3, 2010) — Mental toughness and an aptitude for sport may be biologically determined.

This is one of the findings of an ongoing research project involving post-doctoral and doctoral research by Dr Jim Golby and Jennifer Meggs from Teesside University who will present their work on November 10 at the Division of Sport and Exercise Psychology's Annual Conference being held at the Holiday Inn London -- Camden Lock.

Previous research has shown that the 2D:4D ratio (index finger/ring finger) has the potential to explain sporting success. An index finger that is much shorter than the ring finger is caused by exposure to testosterone in the womb. This research investigated the relationship between 2D:4D and mental toughness, optimism, aggression and performance.

Sixty-seven participants had their fingers measured and completed personality and aggression questionnaires.

The results showed that participants with 2D:4D ratio were more likely to demonstrate mental toughness and have higher levels of sporting achievements.

Dr Golby explained: "It appears that high prenatal levels of testosterone may result in increased mental toughness, optimism and hence aptitude towards sport. This provides tentative support for the conclusion that mental toughness may be partially biologically predetermined."

Osteoarthritis Risk Linked To Finger Length Ratio

..............Professor Michael Doherty, lead researcher, said: “The 2D:4D length ratio appears to be a new risk factor for the development of OA. Specifically, women with the 'male' pattern of 2D:4D length ratio — that is, ring finger relatively longer than the index finger — are more likely to develop knee OA.”

As the first study to examine the relationship between 2D:4D length ratio and OA, it also raises questions.

Finger Length Points to Prostate Cancer Risk

The study led by The University of Warwick and The Institute of Cancer Research (ICR) found men whose index finger is longer than their ring finger were one third less likely to develop the disease than men with the opposite finger length pattern.

"Our results show that relative finger length could be used as a simple test for prostate cancer risk, particularly in men aged under 60," says joint senior author Professor Ros Eeles from the ICR and The Royal Marsden NHS Foundation Trust. "This exciting finding means that finger pattern could potentially be used to select at-risk men for ongoing screening, perhaps in combination with other factors such as family history or genetic testing.".......................

Don

Adrenal Fatigue Symptoms

additional thoughts to adrenal posting..............

Any of these familiar:

• Low body temperature
• Weakness
• Lack of energy (reduced energy metabolism)
• Unexplained hair loss
• Nervousness
• Difficulty building muscle
• Difficulty losing weight
• Irritability
• Mental depression
• Difficulty gaining weight
• Apprehension
• Reactive hypoglycemia (feeling shaky/cranky/palpitations after high carbs)
• Inability to concentrate
• Excessive hunger
• Tendency towards inflammation
• Moments of confusion
• Indigestion, irritable bowel syndrome
• Poor memory
• Alternating diarrhea and constipation
• Osteoporosis, osteopenia, bone fractures 
• Auto-immune diseases
• Poor resistance to infections
• Frequent infections
• Asthma
• Respiratory infections, pneumonia, bronchitis
• Low blood pressure (but high occcurs too)
• Lightheadedness especially upon standing 
• Palpitations [heart fluttering]
• Dizziness that occurs upon standing
• Insomnia
• Food and/or inhalant allergies
• PMS
• Craving for sweets and carby foods
• Dry and thin skin, dry skin, acne
• Headaches, Migraines, Abdominal Refractory Migraines
• Scanty perspiration (or excessive with reactive hypoglycemia)
• Alcohol intolerance
• Caffeine intolerance 
• Iodine intolerance (heart palpitations, racing heart, jittery? probably adrenal fatigue)
• Thyroid replacement intolerance (ditto... with Armour, Cytomel, Synthroid, Levoxyl, Nutri-med Thyroid, etc therapy)

Stages, Tests and Treatment

Stages

Adrenal exhaustion progresses in three (3) stages. Adrenal Function Testing is the most accurate determination of which stage you may find yourself.

Stage I Alarm is distinguished by an increase in output of ACTH by the anterior pituitary gland, increased adrenocortical stimulation, increased cortisol output and an increased probability of pregnenolone steal and decreased DHEA. When in a Chronic Stress Response, pregnenolone, the common precursor to cortisol, DHEA and other hormones is preferentially diverted to cortisol production at the expense of the rest of the steroidal hormones. Generally in Stage I cortisol increases and DHEA and its metabolites decrease or an imbalance occurs especially between testosterone and estrogen.

Increased ACTH and Cortisol. Decreased DHEA. Estrogen and Testosterone imbalance.

Stage II Resistance Adrenal Exhaustion is marked by the transition from increased to decreased cortisol output. This stage is characterized by continuing high levels of ACTH and thus: adrenocortical stimulation, normal total cortisol output, low or borderline low morning, noon or afternoon cortisol levels, normal nighttime cortisol level, and an increased probability of pregnenolone steal and a further decrease in DHEA. This is a transitional phase in which although ACTH stimulation remains high or even increases, the adrenal output of cortisol declines due to the adrenal fatigue associated with continued hyper stimulation.

Increased ACTH. Decreased DHEA and Cortisol. Cortisol rhythm disturbance.

Stage III Failure Adrenal Exhaustion is an advanced stage of adrenal exhaustion characterized by decreased total cortisol output. This stage is characterized by continuing high levels of ACTH and thus adrenocortical stimulation, low total cortisol output, and increased probability of a low nighttime cortisol level and pregnenolone steal and even further decrease in DHEA. The adrenal glands are now exhausted to the point that even though there is ongoing hyperstimulation (high ACTH); they continue to lose their capacity and reserve to produce enough cortisol. The eventual result is a crash of the hypothalamic-pituitary-adrenal axis (HPAA) in which essential neuroendocrine feedback loops are unable to return the system to homeostasis.

Increased ACTH. Decreased DHEA and Cortisol. Cortisol rhythm disturbance; especially at night

FUNCTIONIONAL ADRENAL TESTS

Adrenal Function Tests You Can Do at Home

#1-Postural Hypotension:
Postural hypotension (also known as orthostatic hypotension) is a drop in blood pressure that occurs upon rising from a horizontal position. It is commonly expressed as a feeling of dizziness or lightheadedness, a "head rush", or "standing up too fast".

To do this test, you will need a blood pressure cuff. Lie down and rest for 5 minutes. Take a blood pressure reading while still horizontal. Then, stand up and take another reading.

Normally, your blood pressure should rise 6-10 points. If it drops, particularly by 10 points or more, hypoadrenia is indicated. Generally, the bigger the drop, the greater the adrenal insufficiency.

It should also be mentioned that low blood pressure in general is also an indicator of exhausted adrenals when present in conjunction with the other symptoms of adrenal gland fatigue.

#2-Iris Contraction Test
For this test you will need a weak flashlight or penlight, and a mirror. In a dark bathroom or closet, wait a minute for your eyes to adjust to the dark. This will allow your pupils to dilate (open) fully. Then, shine the flashlight into your eyes, and watch the reaction of your pupils for at least 30 seconds.

The light should cause your iris to contract, making your pupils (the dark spot in the center of your eye) smaller. Normally, they should stay that way, but if you have adrenal gland fatigue, the iris will be weak and will not be able to hold the contraction, it will either waver between contracted and relaxed, or will contract initially, but then open up after 10-30 seconds.

As with the postural hypotension test, the degree to which you "fail" this test is an indicator of the degree of adrenal insufficiency you are experiencing.

#3-Sergent's Adrenal White Line
With your fingernail or the dull end of a spoon, draw a line across your belly. In moderate to severe cases of adrenal fatigue, the line will stay white, and even get wider over the course of time, while a "normal" reaction would be for the line to almost immediately turn red.

This test has historically been used to indicate severe adrenal fatigue and Addison's Disease, milder cases of adrenal fatigue may not exhibit this sign.

Saliva Testing

What is Saliva Testing?

The Cortisol/DHEAS Saliva Test measures the levels of the stress hormones DHEAS and cortisol and provides an evaluation of how cortisol levels differ throughout the day.

Health conditions this test is used to assess
Most saliva hormone tests can uncover biochemical imbalances that can be underlying causes of such conditions as chronic stress, adrenal fatigue, anxiety, chronic fatigue, obesity, diabetes, depression, insomnia, and many other chronic conditions.

What does this test involve?
The test involves simply spitting into a test tube. Cortisol is measured four times - in the morning (8 AM), noon, evening (4 PM) and night (best between 11 PM and midnight). Other steroid hormones, such as estrogen, progesterone, DHEAS and testosterone can be measured along with cortisol in the 8 AM saliva sample, if desired. You carry the test tubes with you during the day (they easily fit into a pocket or purse) so they are handy when it’s time to give a saliva sample. Immediate refrigeration is not necessary. Once the sample set is complete, you mail the tubes back to the lab for analysis in the mailing envelop that is included with the test kit. Both you and your doctor will receive copies of the results, usually within 2 weeks.

Is saliva testing for hormones reliable?
Yes, saliva tests are reliable indicators for all steroid hormones (cortisol and all sex steroids). However just as with blood tests, some labs are more reliable than others – especially for sex steroids, like estrogens. In fact, saliva cortisol testing is covered by Plan B medicare. The National Institutes of Health (NIH) and the World Health Organization (WHO), recognize saliva cortisol testing as being very accurate. Some insurance plans also cover saliva cortisol testing. Since 1983, 2,500 research papers have been published supporting salivary hormone testing.

How can I get this test done?
Talk to your health care professional about your symptoms and ask if this test would be useful for you.

The following laboratory performs salivary hormone testing and can help you find practitioners who are familiar with them:

Diagnos-Techs, Inc.6620 192nd Place, Bldg. J
Kent, WA 98032
425-251-0596
e-mail cs@diagnostechs.com


Treatment

Too often the signs and symptoms of the adrenal cortex are confused with those created by the adrenal medulla and a sympathetic - parasympathetic nervous system imbalance.' On the "Stress Related Illness and the Adrenal Glands" chart is a listing of common signs and symptoms found in stress related patients with a differentiation made between those arising from the adrenal cortex and those attributable to sympathetic - parasympathetic imbalance. It is important to identify whether or not the stress related patient is either sympathetic dominant or parasympathetic dominant because treatment must be varied accordingly.

Sympathetic Dominance Signs

• High Systolic / High Diastolic
• Tachacardia
• Paradoxal pupils
• Energy OK
• Closed ICV
• Decreased Saliva

Parasympathetic Dominance signs

• Low Systolic
• Bradycardia
• Constricted Pupils
• ICV Open
• Energy Low
• Increased Saliva

HyperAdrenal Cortex Signs

• High Diastolic

HypoAdrenal Cortex Signs

• Low Diastolic
• Increased Pulmonary S2

Nutritional Support:

Drenamin is a combination product containing adrenal protomorphogen extract, adrenal concentrate, and the Cataplex "G" (riboflavin and niacin) and Cataplex C. The adrenal gland has both a cortex and a medulla. Drenamin helps to support primarily adrenal cortex function. The adrenal gland cortex is an endocrine gland which makes steroid hormones which are increased under conditions of stress and whose effects last for several hours. It is sometimes necessary to use the protomorphogen extract in combination with the whole glandular concentrate which is supportive of both the cortex and the medulla. The Cataplex "G" and C are substances which the adrenal cortex uses up. Drenamin is important to consider in a patient whose nutritional pattern has been faulty for a long time.

Drenatrophin PMG supports adrenal function. Provides uniquely derived nucleoprotein-mineral extracts that support cellular health. Supports adrenal gland health. Over the long term, helps maintain adrenal function to reduce the effects of stress on the nervous system and combat fatigue.
 
A flexible rule of thumb would be to use Drenamin for patients with high or normal blood pressure and weak adrenals, and Drenatrophin PMG for patients with low blood pressure and weak adrenals.

Frequently, Pantothenic acid (B5) is also required in stress related conditions. Pantothenic acid is essential for the synthesis of steroid hormones in the body including the adrenal hormones. In most patients, 100 mg to 300 mg. of pantothenic acid per day is adequate to combat their stress levels when combined with other natural therapies.

Too often the signs and symptoms of the adrenal cortex are confused with those created by the adrenal medulla and a sympathetic - parasympathetic nervous system imbalance.

The body makes norepinephrine and epinephrine using the following nutrients: the amino acid Tyrosine, Tyrosinase Enzyme and Ascorbic acid (as in CATAPLEX C), Folic Acid, B-6, Niacinamide, and Iron.

Alkaline ash minerals will affect tissue response in such a way as to enhance parasympathetic and dampen sympathetic dominance. The alkaline ash minerals, as found in Organically bound minerals enhance the parasympathetic nervous system which is the body's brake. Alkaline ash minerals are predominantly potassium and magnesium but thi products also contain calcium and a number of other minerals. organically bound minerals tablets are a particularly good source of magnesium, not so much in quantity, but in function in the body. They are also an excellent source of potassium. The potassium, magnesium, and other alkaline ash minerals found in organically bound minerals come primarily from green leafy vegetables. In general, alkaline ash minerals are found in fruits and vegetables.

Herbs

Rehmannia
Rehmannia is the most important Chinese herb for disorders of the kidneys and adrenal glands. Rehmannia also appears to combat adrenal suppression caused by steroid hormones and has a similar tonic effect on the adrenal cortex as licorice. Unlike liquorice (also an adrenal tonic), rehmannia is suitable for use in patients with hypertension (high blood pressure).

Licorice
Its affinity for the endocrine system makes licorice a most remarkable herb, which when used judiciously can be very helpful in treating many human ailments. Licorice has an anti-inflammatory, antiallergic and antiarthritic effect similar to that of cortisone but without its side effects. This is because of glycyrrhizin which has a structure similar to hormones produced by the adrenal glands (cortisol). This occurs because licorice slows the breakdown of cortisol produced by the body.

Adaptogens

The term adaptogen is used by herbalists to refer to natural herb products which they believe increase the body's resistance to stress, trauma, anxiety and fatigue. Adaptogens can also be called rejuvenating herbs, qi tonics, rasayanas, or restoratives. One specific characteristic of their action is that their effect is believed to help the body return to a balanced state. Some herbologists claim that adaptogenic herbs are distinct from other substances in their ability to balance endocrine hormones and the immune system, and they help the body to maintain optimal homeostasis. Adaptogens are purported to have a normalizing effect on the body and to be capable of either toning down or strengthening the activity of hyperfunctioning systems.

Withania (Ashwaganda) Complex
An effective combination of Ashwaganda (Withania), Skullcap, Licorice and Korean Ginseng to support both adrenal and nervous system health. A wonderful whole body tonic to promote vitality and stamina in people of any age. The combination of adrenal and nervous system support helps to promote relaxation and the body's ability to adapt to temporary stress. Supports HPA axis. Specialized testing techniques used by MediHerb ensure that the correct plant parts containing appropriate levels of active constituents are used, which is particularly important for both Ashwaganda and Korean Ginseng.

Eleuthero
An effective herb revered in Russia to support the body's ability to adapt to temporary stress. Supports the HPA axis. Eleuthero has been shown to restore and enhance immune system function. A wonderful whole body tonic that promotes vitality, and physical and mental endurance. MediHerb's Eleuthero contains 950 mcg of eleutheroside E to ensure quality and optimal clinical results.

Rhodiola and Ginseng Complex
Combines two powerful tonic herbs, Rhodiola and Korean Ginseng, to promote energy, vitality and stamina. Ideal formula to support physical and mental performance. Korean Ginseng and Rhodiola contain guaranteed levels of active constituents to ensure optimal quality and clinical results.

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Adrenal Output

MINERALOCORTICOIDS (Zona Glomerulosa)

• Endogenous produced by zona glomerulosa.
• Aldosterone and others regulate intravascular volume and blood pressure.
• Aldosterone works on renal tubule.
• Aldosterone; Na+, bicarbonate (chloride) and H2O retention, decreasing resorption of potassium.
• Clients with Addison's disease have low minieralocorticoid production.
• Aldosterone levels are increasing in Conn's syndrome.
  

Formation of Mineralcorticoids

Physiologic Effects of Mineralocorticoids

Mineralocorticoids play a critical role in regulating concentrations of minerals - particularly sodium and potassium - in extracellular fluids. As described above, loss of these hormones leads rapidly to life-threatening abnormalities in electrolyte and fluid balance. Hyposecreation can lead to decreased blood volumethat can result in decreased cardiac output and hypotension. Hypersecreation can result in increased volume of extracellular fluid which leads to increased volume of the blood which can increase cardiac output ultimately resulting in hypertension.

The major target of aldosterone is the distal tubule of the kidney, where it stimulates exchange of sodium and potassium.

Three (3) primary physiologic effects of aldosterone:

1. Increased resorption of sodium: sodium loss in urine is decreased under aldosterone stimulation.
2. Increased resorption of water, with consequent expansion of extracellular fluid volume. This is an osmotic effect directly related to increased resorption of sodium.
3. Increased renal excretion of potassium.

Knowing these effects should quickly suggest the cellular mechanism of action this hormone. Aldosterone stimulates transcription of the gene encoding the sodium-potassium ATPase, leading to increased numbers of "sodium pumps" in the basolateral membranes of tubular epithelial cells. Aldosterone also stimulates expression of a sodium channel which facilitates uptake of sodium from the tubular lumen.

Aldosterone has effects on sweat glands, salivary glands and the colon which are essentially identical to those seen in the distal tubule of the kidney. The major net effect is again to conserve body sodium by stimulating its resorption or, in the case of the colon, absorption from the intestinal lumen. Conservation of water follows conservation of sodium.

Control of Aldosterone Secretion
Control over aldosterone secretion is truly multifactorial and tied into a spider web of other factors which regulate fluid and electrolyte composition and blood pressure. If the major effects of aldosterone are considered, it is rather easy to predict factors which stimulate or suppress aldosterone secretion.

The two (2) most significant regulators of aldosterone secretion are:

1. Concentration of potassium ions in extracellular fluid: Small increases in blood levels of potassium strongly stimulate aldosterone secretion.
2. Angiotensin II: Activation of the renin-angiotensin system as a result of decreased renal blood flow (usually due to decreased vascular volume) results in release of angiotensin II, which stimulates aldosterone secretion.

Other factors which stimulate aldosterone secretion include adrenocorticotropic hormone (short-term stimulation only) and sodium deficiency. Factors which suppress aldosterone secretion include atrial naturetic hormone, high sodium concentration and potassium deficiency.

GLUCOCORTICOIDS (Zona Fasciculata)

• endogenous released on diurnal cycle from zona fasciculata.
• exogenous are most potent anti-inflam medications available.
• synthetic drugs mb 20-100x more potent than endogenous cortisol.
• cortisol is principle endogenous one.
• binds to cell receptors;changes gene transcription and behavior of cells.
• promotes gluconeogenesist; increasing blood sugar to deal with stressor (trauma, infection, disease).
• regulates metabolism of proteins, carbohydrates, lipids.
• causes mild increase in blood pressure thru vasoconstriction.
• increase in circulating of neutrophils, HGB, RBC's.
• decrease circulating of lymphs including T cells, eosphils, basophilss, monosites, and macrophages.
• pharmacologic doses dramatically reduce accumulation of leukocytes and inhbits chemotactic signalling.
• also inhibits access of leukotrines to inflammation sites, intereferes with fixation of leukotrines and fibroblasts.
• inhibition of phospholipase A2; blocks release of arachadonic acid; no new prostaglandins or leukotrines.
• anti-inflammation effect due to decreased production of prostaglandins.
• also suppresses histamine release and kinin activity.
• metabolized by liver microsomal oxidizing enzymes.

Control of Cortisol Secretion
Cortisol and other glucocorticoids are secreted in response to a single stimulator: adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH is itself secreted under control of the hypothalamic peptide corticotropin-releasing hormone (CRH). The central nervous system is thus the commander and chief of glucocorticoid responses, providing an excellent example of close integration between the nervous and endocrine systems.

Virtually any type of physical or mental stress results in elevation of cortisol concentrations in blood due to enhanced secretion of CRH in the hypothalamus. This fact sometimes makes it very difficult to assess glucocorticoid levels, particularly in animals. Observing the approach of a phlebotomist, and especially being restrained for blood sampling, is enough stress to artificially elevate cortisol levels several fold!

Cortisol secretion is suppressed by classical negative feedback loops. When blood concentrations rise above a certain theshold, cortisol inhibits CRH secretion from the hypothalamus, which turns off ACTH secretion, which leads to a turning off of cortisol secretion from the adrenal. The combination of positive and negative control on CRH secretion results in pulsatile secretion of cortisol. Typically, pulse amplitude and frequency are highest in the morning and lowest at night.
 
 

ACTH binds to receptors in the plasma membrane of cells in the zona fasiculata and reticularis of the adrenal. Hormone-receptor engagement activates adenyl cyclase, leading to elevated intracellular levels of cyclic AMP which leads ultimately to activation of the enzyme systems involved in biosynthesis of cortisol from cholesterol.

Physiologic Effects of Glucocorticoids

There seem to be no cells that lack glucocorticoid receptors and as a consequence, these steroid hormones have a huge number of effects on physiologic systems. That having been said, it can be stated that the best known and studied effects of glucocorticoids are on carbohydrate metabolism and immune function.

Effects on Metabolism

The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism. In the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. These effects include: 

•Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and lipids and is particularly important in carnivores and certain herbivores. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best known metabolic function of glucocorticoids.

•Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis.

•Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose.

•Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis.

Effects on Inflammation and Immune Function

Glucocorticoids have potent anti-inflammatory and immunosuppressive properties. This is particularly evident when they administered at pharmacologic doses, but also is important in normal immune responses. As a consequence, glucocorticoids are widely used as drugs to treat inflammatory conditions such as arthritis or dermatitis, and as adjunction therapy for conditions such as autoimmune diseases.

Other Effects of Glucocorticoids
Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. 

Several aspects of cognitive function are known to both stimulate glucocorticoid secretion and be influenced by glucocorticoids. Fear provides an interesting example of this. Fear-inducing stimuli lead to secretion of glucocorticoids from the adrenal gland, and treatment of phobic individuals with glucocorticoids prior to a fear-inducing stimulus can blunt the fear response.

Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption and delayed wound healing. These observations suggest a multitide of less dramatic physiologic roles for glucocorticoids.

Next: Catacolemines the Forgotten Adrenal Hormones..............................................

The Adrenals - Introduction

This is a multi part piece about: The Adrenal Gland Function, Assessment and Resolution.

GENERAL

The two adrenal glands are located immediately anterior to the kidneys, encased in a connective tissue capsule and usually partially buried in an island of fat. Like the kidneys, the adrenal glands lie beneath the peritoneum.

CIRCULATION

• tied with thyroid for greatest blood supply/gram of tissue
• up to 60 arterioles enter each adrenal

Inspection of an adrenal gland that has been sectioned reveals two distinct regions. The medulla and the Cortex.

• An inner medulla, which is a source of the catecholamines epinephrine and norepinephrine. The chromaffin cell is the principle cell type. The medulla is richly innervated by preganglionic sympathetic fibers and is, in essence, an extension of the sympathetic nervous system.

• An outer cortex, which secretes several classes of steroid hormones (glucocorticoids and mineralocorticoids, plus a few others). Histologic examination of the cortex reveals three concentric zones of cells that differ in the major steroid hormones they secrete.

Despite their organization into a single gland, the medulla and cortex are functionally different endocrine organs, and have different embryological origins. The medulla derives from ectoderm (neural crest), while the cortex develops from mesoderm.

They sit on top of kidneys, make corticosteroids (cortisol), mineralocorticoids (aldosterone) and catecholamines (dopamine, epinephrine and norepinephrine), also sex steroids (DHEA, progesterone, estrogen, testosterone).

• Surrounded adipose capsule and the renal fascia
• Located at about T11-12
• right side lower due to liver taking up space.

Removal of the adrenal glands leads to death within just a few days. Observation of such an unfortunate subject would reveal several key derangements:

•The concentration of potassium in extracelluar fluid becomes dramatically elevated.
•Urinary excretion of sodium is high and the concentration of sodium in extracellular fluid decreases significantly.
•Volume of extracellular fluid and blood decrease.
•The heart begins to function poorly, cardiac output declines and shock ensues.

These phenomena are a direct result of loss of mineralocorticoid activity, and can largely be prevented by replacement of salts and mineralocorticoids. Clearly mineralocorticoids are acutely critical for maintenance of life!

In contrast to loss of mineralocorticoids, failure to produce glucocorticoids is not acutely life-threatening. Nevertheless, loss or profound diminishment of glucocorticoid secretion leads to a state of deranged metabolism and an inability to deal with stressors which, if untreated, is fatal.

In addition to their physiologic importance, glucocorticoids are also among the most frequently used drugs, and often prescribed for their anti-inflammatory and immunosuppressive properties.

Adrenal Gland

The zona fasciculata and zona reticularis, which are both normally activated by ACTH from the anterior pituitary, would atrophy, so that you'd have less adrenal production of cortisol and sex steroids. The glomerulosa (produces aldosterone) and the medulla (produces dopamine, epinephrine and nor-epinephrine) would be unaffected.

Medulla
The adrenal medulla is really an extension of the central nervous system and secretes the catecholamines norepinephrine (noradrenalin) and epinephrine (adrenalin) in response to stimulation of the sympathetic nervous system. These substances aid in the "fight or flee" reaction in response to immediate stress. When these catecholamines are released into the general circulation, their effects last from 30 seconds to two minutes.

Chromaffin cells (derived from neural crest) are main source of catecholamines.

• Main source of Dopamine, precursor of Epinephrine & Norepinephrine.
• Catecholamines are water soluble, derived from amino acid tyrosine.
• Adrenal medulla is from ectoderm tissue in embryo.
• Considered specialized ganglia of the sympathetic nervous system.
• Releases hormones into the blood.

Cortex Three (3) Layers of Cortex: Zonas
Makes corticosteroid hormones from:

HPA axis controls cortisol/corticosterone synthesis

• Normal production: 35–40 mg of cortisone acetate per day
• Also makes androgens: testosterone
• Also regulates water and electrolyte concentrations via aldosterone
• Cortex regulated by neuroendocrine hormones from pituitary gland and by renin-angiotensin system (Aldosterone)

Cortex Zonas

• Zona Glomerulosa makes mineralocorticoids (aldosterone)
• Zona Fasciculata makes glucocorticoids (cortisol)
• Zone Reticularis makes sex steroids (DHEA)

ZONA GLOMERULOSA

• Mineralocorticoids including aldosterone
• Aldostone release provoked by RAA system, triggered by low blood volume
• Aldosterone; distal convoluted tubules excrete K+, reabsorbtion Na+ and H2O--> increase volume and blood pressure.
• Licorice works to increase blood pressure by increasing mineralocorticoid production

ZONA FASCICULATA

• glucocorticoids including cortisol and corticosterone
• stimulated by ACTH from anterior pituitary-->increased cAMP
• some cortisol secretion persists even when there's not ACTH

ZONA RETICULARIS

Makes DHEA (dehydroepiandrosterone) in response to ACTH signal from anterior pituitary which is controlled by hypothalamic signaling and other sex steroids too: estrogen, testosterone.

next Mineralcorticosteriod & Glucocorticosteroid..............................