more old posts-shelia found this--

February 24, 2004

Adrenals

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IMPLICATIONS OF ADRENAL INSUFFICIENCY

by J. Ghen, D.O., Ph.D., and C. Barton , M.D., M.P.H.,

F.A.A.F.P.

A nutritional program that does not address adrenal insufficiency

issues may eventually fail. Physicians and other healthcare

practitioners often misdiagnose adrenal insufficiency. In this

article, we will discuss the signs, symptoms, etiologies, diagnosis,

and possible treatments from both a conventional and complementary

perspective.

DEFINING THE ADRENALS

The adrenal glands are paired structures that are located

retroperitoneally at the upper pole of each kidney. Two distinct

regions of this organ are noted. The golden yellow outer portion of

the gland is the adrenal cortex, and the inner portion is called the

medulla. Above is a schematic of the hormones produced by the adrenal

cortex.

The functions of the medulla and cortex are distinctly different. The

cortex is responsible for the production of four major hormones. The

primary one is cortisol, a glucocorticoid involved in multiple

biological processes, including glucose control; carbohydrate, fat,

and protein metabolism; inflammatory regulation; intestinal and colon

membrane repair; and the stress response. The second, aldosterone, a

mineral-corticoid, is directly involved in the renin-angiotensin-

aldosterone feedback loop that regulates renal potassium excretion

while preserving sodium by re-absorption. Third, this important

structure produces dehydroepiandrosterone (DHEA), DHEA is a well-

known sex hormone precursor and immune system enhancer. Finally,

pregnenolone is also produced in this area. Pregnenolone is a

precursor to DHEA, with a predilection to cascade down to

progesterone.1

The medulla portion of the adrenal gland is primarily involved in the

secretion of norepinephrine and epinephrine (adrenaline). This is the

area that is responsible for preparing the body for the " fight-or-

flight " response. These hormones can set the tone of the adrenergic

(sympathetic) nervous system.2 Hypertonacity of the sympathetic

nervous system increases the heart rate, raises blood pressure and

blood sugar levels, and dilates the eyes and bronchial tubules.

ADRENAL DISORDERS

Primary adrenal cortical generalized disorders (those related

directly to the gland) may be divided into four categories. Milder

degrees of adrenal insufficiency lack the classic features of

's disease. In " low adrenal reserve, " the mildest form, the

adrenals can still produce sufficient hormones to maintain an

apparently normal state of health in the absence of significant

stress. However, when stressful conditions increase the demand for

adrenocortical hormone, symptoms ranging from fatigue to complete

collapse may occur. Many conditions are linked to psychological

stress, such as angina, asthma, autoimmune diseases, adult diabetes

mellitus, colds, hypertension, and menstrual irregularities. Add to

these the ailments noted earlier, and it is easy to see that many

different health problems influence overall adrenal function.3 Many

practitioners encounter, on a daily basis, patients with this type of

relative adrenal insufficiency as opposed to overt failure. There is

no clear-cut presentation of patients with adrenal fatigue issues.

The four primary adrenal deficiencies are:

1. 's disease, a failure of the adrenal cortex, is often

caused by autoimmune phenomenon, tuberculosis, metastatic carcinoma,

lymphoma, hemorrhage, fungal infection, sarcoidosis, and

hematomacrosis. A drop in IgA can increase intestinal permeability.

In turn, that may exacerbate or cause autoimmune diseases, eventually

leading to cortisol depletion.4 A decrease in IgA would allow for a

translocation of bacteria into the bloodstream, which in turn would

stimulate interleuken release. This would then stimulate the

hyperthalamic pituitary adrenal (HPA) axis, which would lead to a

further demand for cortisol, eventually causing a relative deficiency.

2. Other causes of adrenal insufficiency are hereditary, congenitally

acquired, vascular spasm, degeneration, traumatic and chemical,

nutritional deficiencies, and electromagnetic energy fields.

Aliphatic compounds cause necrosis of the zona faciculata and zona

reticularis where the glucocorticoids are produced. Organic chlorine

compounds and carbonates have caused histological changes to these

areas in animal models. Dioxins and fire ant poison directly suppress

glucocorticoid synthesis, resulting in hypoglycemia.5,6

Other chemicals implicated in adrenal insufficiency include tobacco,

alcohol, street drugs, heavy metals, sugar, coffee, pollution,

pesticides, herbicides, and fungicides. White flour can also cause

these problems. According to Seyle, the difference between whether or

not stress is harmful depends upon the " strength of the system " .7

This is related not only to adrenal reserve, but also to the closely

related issue of dietary intake. Refined carbohydrates (e.g., sugar

and white flour) tax the body's nutritional reserves. While

contributing very few of the nutrients required for their metabolism,

they deplete a great deal of the nutrients also necessary for adrenal

support, especially B vitamins.8

The authors also believe that extremely low-frequency electromagnetic

fields from computers, hair dryers, airplanes, and electric blankets,

can damage this vital tissue.9-10

SECONDARY DISORDERS

Secondary disorders can also cause adrenal corticol deficiency. These

include nonsteroidal anti-inflammatory drugs and pituitary disease,

which are unrelated to the adrenal gland itself. Even oversecretions

of the medulla can affect cortical function. A stressor creating

a " fight-or-flight " response releases adrenaline.

Note: " Stress " is defined in a physiological context as any factor

that acts to destroy homestasis. More pecisely, it is the body's

response to any factors that threaten its ability to maintain

homeostasis.34

Adrenaline release also causes liver glycogen stores to free glucose.

In addition, the hypothalamic/pituitary access is stimulated, as ACTH

and beta endorphin are released. Finally, the adrenal gland increases

cortisol output and decreases DHEA production. This cascade will

affect sex hormone production by decreasing testosterone and estrogen.

For many women, the transitional stage of life leading to menopause

is fraught with unacceptable and well known symptoms, caused by

decreased ovarian hormone production. In a healthy woman, the adrenal

glands take over harmonal production to some degree. Many women,

however, approach menopause in a state of chronic emotional and

nutritional depletion, which affects optimal adrenal function.35,36 A

secondary side effect of this stress response is decreased mental

clarity due to the hippoocampus's chronic exposure to cortisol.37

The father of modern stress research, Hans Selye, described the

stress response as a part of the larger " general adaptational

syndrome. " This syndrome is composed of three phases:

· Alarm

· Resistance

· Exhaustion

Reactions in the brain trigger the alarm reaction, also known as the

fight-or-flight response. These reactions ultimately cause the

pituitary to release ACTH, which in turn causes the adrenals to

release stress-related hormones, such as adrenaline. This short-lived

phase is followed by the resistance phase, which allows the system to

continue its adaptation to stress long after the alarm phase effects

have worn off. Corticosteroids, such as cortisol, mediate this

response. However, if prolonged, stress reaches the final phase,

which is exhaustion.38,39

3. Bilateral adrenalectomy refers to the removal of both adrenal

glands.

4. Adrenal enzyme deficiency is the other disorder of the adrenal

cortex that can lead to primary adrenal cortex insufficiency.11

INTEGRATIVE TREATMENT PROTOCOL

If the patient exhibits decreased levels of cortisol at all

examinations, clinical repletion with hydrocortisone (possesses both

glutacorticoid and mineralocorticoid activity) is usually effective.

Results are quick and reliable, According to the work of M.

Jeffries, cortisol, when properly administered, is as safe as any

other naturally produced hormone. The ill-informed use of higher

pharmacologic doses, with their devastating side effects, has

engendered an unwarranted degree of caution when addressing cases of

documented adrenocortical hypofunction. The evidence supports the use

of physiologic sub-replacement doses (5mg or less q.i.d.) in these

patients. Low doses result in neither hypercortisonism, nor

significantly impaired resistance to stress.12 The rationale here is

similar to that seen with inappropriate dosing of human growth

hormone (HGH), which may cause acromegaly. However, this does not

preclude the prudent use of physiologic doses.

Using herbal and other nutraceuticals (e.g., vitamins, minerals, and

amino acids) does not seem to afford the clinician with the control

nor the response needed in these severely depressed individuals. We

recommend prescribing a three-month supply of hydrocortisone and

carefully monitoring the patient with regular monthly visits. After

90 days, add one or two of the nutraceuticals listed under " Specific

recommendations " (right).Then gradually reduce and eliminate the

hydrocortisone over a 2-week to 30-day period. If the gland is still

not operating appropriately, further drug repletion may be necessary.

Certain individuals may require hydrocortisone on a life-long basis.

If you are going to stop the use of corticosteroids, it is best to

taper the drug so as not to create a frank adrenal failure. Although

this would be unusual in such low doses, it is best to reduce the

dose in half for one week, and then half again for another week, and

then stop.

SYMPTOMS OF ADRENAL INSUFFICIENCY

The most common presenting symptoms of chronic primary adrenal

cortical insufficiency are weakness, fatigue, weight loss, and

anorexia. Low blood pressure, salt cravings, gastrointestinal

symptoms, and hyperpigmentation can also be seen in these patients,

Non-specific symptoms are commonly seen in marginally deficient

patients.These may include poor mental clarity, decreased sexual

function, decreased libido, and just not " feeling right: "

SPECIFIC RECOMMENDATIONS

1. If DHEA levels are low, replacement is required. Normal ranges for

salivary levels are 3-10 ng/ml, with 8-10 ng/ml reflecting the best

immune function. Typically, patients with chronic diseases exhibit

low or below-normal levels, both of which should be treated

aggressively. In the absence of frank adrenal failure, we have found

that rheumatoid arthritis, fibromyalgia, and even polyneuropathy will

usually respond to DHEA rather than other drugs. "

2. All patients should be encouraged to:

a) Stop smoking;

Discontinue any street drugs;

c) Decrease alcohol consumption;

d) Decrease intake of fats, salt, and sugar;14

e) Decrease caffeine consumption,

f) Exercise aerobically at least three hours a week;

g) Use stress-reduction techniques such as prayer, meditation,

soothing music, funny movies,

h) guided imagery, or biofeedback 15

i) Get professional help to deal with anger and rage, and deal with

psychospiritual issues that surround work, family, care-giving, self-

esteem, and body image, which may help reduce cortisol levels; and

j) Limit exposure to extremely low-frequency magnetic energy fields.

3. If secretory IgA levels are low, repair the probable intestinal

permeability with L-glutamine, an amino acid often taken from lung

and bone to replenish the supply for the enterocytes and coloncytes.

Also, immunoglobulin repletion with a whey product high in

immunoglobulin IgA, or the inclusion of eggs in the diet, may be

helpful. Melatonin has also been shown to improve secretary IgA.16

4. Based on our observations, we recommend an optimal ratio of omega-

3 and omega-6 oils (4: 1).

5. Suggest increasing intake of pantothenic acid (vitamin B5 ).

Eating more whole grains and eggs will increase this vital

nutrients.17

6. Recommend 2-5 grams of potassium a day.18

7. Vitamins C (1,000-2,000mg/day) and B6 (100-300mg/day) are vital

nutrients for adrenal function.

8. Zinc (50mg/day) and magnesium (500mg/day) are recommended.19

9. The herb ashwagandha may be helpful. Several adaptogens, such as

ginseng (Panax equals Korean/Chinese), provide tonic effects.20 Make

sure that this adaptogen contains 25-50mg of ginsenosides in daily

divided doses. This usually translates to 1-2 grams per day Ginseng

has been shown to amplify the glandular effects. It does this by

increasing the responsiveness of the adrenal gland and the ability to

control the gland secretion. Use short, 90-day courses of ginseng,

and alternate this with licorice derivatives.

10. Licorice has aldosterone-like properties.21 It can be helpful in

adrenal corticoid abnormalities. Glycyrrhetinic acid is a pentacyclic

triterpene derivative of the b-amine type. This substance also

exhibits regulatory action on the adrenal gland.22

11. Soluble adrenal fractions, a nutraceutical, can stimulate a

sluggish gland to become more productive. Increase this product until

there are symptoms of nervousness or difficulty sleeping. Then reduce

the dose slightly until there are no more undesirable side effects.

12. Individuals in a chronic stress state often have an increase in

their phenylatanine-tyrosine ratio. Both tyrosine and phenylalanine

restore epinephrine levels.23 Multiple studies have documented

beneficial results in fatigue and depression by using supplemental

phenylalanine or tyrosine. Phenytalamne is decarboxylated to

phenylethylamine (PEA), which has amphetamine-like stimulant

properties (found in high concentrations in chocolate). Phenylalanine

is also hydroxylated to tyrosine, which eventually forms epinephrine.

However, its primary supplemental effects are thought to be through

the former pathway. Tyrosine, which is necessary for the formation of

nonepinephrine, is found at low levels in depressed patients.

Supplementation increases levels of 3-methoxy-4-hydroxyphenethylene

glycol (MHPG) in the urine. This is probably the principle breakdown

product of norepinephrine in the central nervous system (CNS), and

may provide a marker to determine which amino acid to supplement.24,25

13. Check patients for heavy metal intoxication. Remove any heavy

metal burdens with an appropriate chelating agent.26,27

14. Coenzyme Q1O, and two digestive enzymes.28

15. Desiccated adrenals can be used for a short time.29

16. Vitamin A may help correct abnormal exhaustion.30

SUMMARY

The clinician's lack of response to compromised adrenal function can

have deleterious effects on the patient. You will find that your

nutritional program falls short of your goals. In less-than-severe

adrenal insufficiency (adaptive phases vs. maladaption), add the

nutrients described. Monitor your success by repeating the salivary

testing every 90 days until the situation is corrected. If your

regimen fails, consider the following possibilities:

1. Your dosage was too low.

2. Your length of treatment intervals before retesting were too short.

3. Patient compliance was poor. Make sure the patient is taking the

prescribed dosage.

4. External causes were not eliminated.

5. IgA levels did not improve.

6. If the patient was not responding well to the supplements he or

she was taking, make sure the supplements come from a company that

uses pharmaceutical-grade nutrients.

7. Conventional treatment and/or nutraceuticals did not effectively

address underlying disease pathology.

8. Patient's medications were hindering an optimal result.

9. Chronic anxiety and/or depression were not adequately treated.

10. Food allergies had a negative effect on result. For example, when

IgA is low, foreign substances, including incompletely digested bits

of food, can enter the circulation and become antigens.31,32

11. Bioavailability should also be considered in treatment

evaluation. For example, does the patient have adequate hydrochloric

acid for the initial dissolution of the prescribed product? Is gut

dysbiosis preventing appropriate absorption?

If all the above possibilities have been explored and the patient is

still not responding well, try a short course of hydrocortisone and

note the effect. A measurement of plasma renin activity can help you

assess the need for mineral corticoid replacement therapy. The

clinician should measure blood pressure using a tilt table, if not

available, test the patients blood pressure, in both arms, in lying,

sitting, and standing positions. Patients may require the addition of

fludrocortisone, a mineralocorticoid.33

DIAGNOSING ADRENAL INSUFFICIENCY

The practitioner must correlate the history presented with the

physical examination. When adrenal insufficiency is suspected, the

following workup might be necessary.

Serial saliva testing is the easiest and most convenient way to

diagnose adrenal cortical deficiency. Patients are sent home with a

simple kit. Early morning noon, dinner, and PM samples are obtained

by soaking a cotton ball with saliva. Lab results of this test can

give accurate information about cortisol levels, DHEA, anti-gliadin

antibodies, and secretary IgA. The salivary ACTH test has been shown

to be 1,000 times more sensitive than serum testing. 40 This type of

serial evaluation is necessary, considering the fact that secretion

of adrenocordcotropin and subsequent cordcotropin-releasing hormone

(CRF) are pulsatile and manifest diurnal circadian rhythm. 41,42

Utilizing the results of this test makes it easier to develop the

best treatment strategy. Consider asking the lab to do a 24-hour

urinary excretion for 17-hydroxycortical steroids.

If done conventionally, adrenal responsiveness can be determined at

any time of day. However, it is possible that milder degrees of low

adrenal reserve may not be detected unless ACTH tests are performed

in the morning, at the time when plasma cortisol levels are the

highest. The best conventional screening test is to measure a serum

cortisol before, and 30-60 minutes after, an IV or IM injection of

0.25 mg synthetic ACTH. A normal response would be a rise in the

serum cortisol level of two to three times baseline, or a peak

response no less than 15 mcg/ 100 ml.43,44

CONCLUSION

Careful examination of the chronically ill patient often reveals

significant adrenal insufficiency The system cannot support adequate

immune function without hormonal health. Use of supplemental hormones

may be necessary.

Practitioners with the appropriate license and knowledge can join

your health team. Combining conventional and complementary approaches

will give your patients the proper support they need, and reward you

with a profound sense of accomplishment.

March 1, 2004

thanks, Tina...very interesting stuff...need to read it again.

Did you notice this...

SECONDARY DISORDERS

Secondary disorders can also cause adrenal corticol deficiency. These

include nonsteroidal anti-inflammatory drugs and pituitary disease,

which are unrelated to the adrenal gland itself.

I've never heard of this before? You?

thanks! I gotta hit the sack...need sleep. thanks for this. hugs, sheila

tina83862 <tina83862@...> wrote: