THE DISCOVERY OF AN ANIMAL MODEL THAT IS SIMILAR TO CONGENITAL ADRENAL HYPERPLASIA (CAH), NON CLASSIC CONGENITAL ADRENAL HYPERPLASIA (NC-CAH), AND POLYCYSTIC OVARIAN SYNDROME (PCOS), WHICH MAY IDENTIFY THE CAUSE OF THESE SYNDROMES AND NOT JUST THEIR EFFECTS
By Alfred J. Plechner, D.V.M.
Several years ago, I discovered a syndrome in dogs, cats and horses that caused these animals to develop clinical signs similar to the symptoms found in humans with CAH, NC-CAH and PCOS.
The syndrome for this animal model I call Atypical Cortisol Estrogen Imbalance Syndrome (ACEIS) or as the public refers to it as Plechner’s Syndrome (PS).
I would like to begin this article from an informational standpoint with a general comparison of these various syndromes.
NC-CAH produces less severe symptoms than Congenital Adrenal Hyperplasia (CAH) which is similar but recognized earlier in infants and young children.
CAH usually begins at an early age with possible abnormal male and female genitalia, failure of normal growth and normal height, hypertension, mental changes, early puberty and acne.
These medical effects may vary slightly from patient to patient.
NC-CAH may demonstrate similar symptoms but the symptoms seem to be less severe and are often seen in slightly older patients.
NC-CAH symptoms can also include premature pubic hair development, body odor, persistent acne, irregular menstrual cycle, reduced sperm counts, excess facial hair, oily hair and skin, mood swings, depression and anxiety.
PCOS symptoms often manifest themselves clinically with irregular menstrual cycles, signs of excess male hormones in females called androgen, polycystic ovaries, ovarian cysts, acne, fatigue, weight gain, skin tags, hyper pigmentation, dandruff, insulin resistance, mood swings, high cholesterol, high blood pressure, sleep apnea, including a myriad of syndromes like Turners, Kline fellers and Downs etc.
These various syndromes are similar but are different and seem to be based upon collecting a list of different symptoms or medical effects and then classifying these various symptoms and effects as one major disease or another.
A friend of mine is the expert in the field of Teratology which is the study of the causes and effects of congenital malformations and development of recognizable physical abnormalities.
She has been able to show that certain recognizable features in specific populations of people will have or will develop a number of different hormonal imbalances and syndromes of which CAH, NC-CAH and PCOS may be among them.
Talon cusps are easily identified, as are shovel teeth, are dental malformations.
Also the presence of a single transverse palm crease is another physical malady that was once referred to has a ”simian” palm crease, which is different in most people which have three transverse palm creases.
These physical changes occur mainly in Eskimos, Aleutians, Native American Indians and some Chinese.
These races of people were thought to extend from the Siberian population many centuries ago.
I quote from the literature, “an extremely rare mutation of the Y chromosome may be the genetic marker that is unique to the people that migrated to the Americas 30,000 years ago”.
To read more, please go to http://sarahredhead.hubpages.com/hub/TEETH-Clues-To-Your-Ancestry.
Her findings are monumental yet are still not well accepted and understood by the medical community.
She does refer to her observations as Zebra Fever.
It is vital for a medical practitioner to first observe this physical maladies in a patient before recommending any diagnostics.
What is accepted and understood by the medical community is that the cause of these various syndromes are not known but there are available treatments to try.
However, the cause of this animal syndrome can be determined with a simple blood test, which may also be applied to humans that have these similar syndromes.
Once controlled and properly funded, the disease effects that are caused by the imbalance in this animal model, can be corrected and controlled.
What is hopefully being realized is that the endocrine system regulates the immune system and unless you realize this and limit your testing to only to hormone levels in the patients, there is no way to know if those hormone levels can be used by the body to fulfill their function.
Your hormone levels must be compared to not only other hormone levels but also to immunoglobulins to determine if any particular hormone you are researching is actually active.
I believe it is agreed upon, but not well understood, that the adrenal gland and its many functions when damaged or deficient, may play a major role in the development of these various but similar syndromes.
It is my opinion that the middle layer adrenal cortex, referred to as the zona fasiculata, when not producing proper amounts and proper types of cortisol, will cause the beginning development of theis various types of syndromes.
When cortisol is produced, it fulfills its functions and as the liver catabolizes the cortisol that is present in the blood stream, the pituitary gland releases it hormone ACTH.
Because of the negative feedback between the pituitary and the middle layer of the adrenal cortex, more cortisol is then released.
I have found with my animal model, that if the cortisol is deficient, defective or bound, the negative feedback mechanism to the pituitary gland will not work properly and will turn into a positive feedback mechanism to the inner layer adrenal cortex and causes an excess production of ACTH by the pituitary to keep the direct cycle going.
When this occurs, the inner layer adrenal cortex responds to the ACTH by producing excessive amounts adrenal estrogen and androgen which may cause many of the damaging clinical effects that are seen with people and animals that have these various syndromes.
It is recognized that excess androgen can cause excess facial hair, acne, aggression including an alpha personality, and abnormal behavior.
When this occurs in female animals, they can act like males animals and not only mount other females sexually but will often mark their territory with their urine and often lift their rear leg to urinate like a male.
They often show extreme behavior creating major destruction of furniture and other objects, aggression towards owners, other people and other animals which is thought to come from the elevated adrenal estrogen due to the cortisol imbalance and excess production of pituitary ACTH.
It is further recognized clinically, that an enzyme which occurs in the fat and other tissues in the body referred to as Aromatase, can turn androgen and testosterone into further estrogen.
When estrogen is measured in human patients, only ovarian estrogen is usually measured in females and usually only estradiole is measured in males and not total estrogen.
This is one of the main reasons catastrophic diseases in people and animals have been missed.
This animal model does measure total estrogen and I know with these human syndromes, total estrogen must be measured otherwise the cause of these syndromes will rarely be found.
What does the elevated adrenal and total estrogen do?
In certain patients, total estrogen can cause the creation of a Reverse T3 and can bind the receptor sites for the T3 hormone.
Often a high T4 and low T3 may be found with these syndromes and may indicate an imbalanced cortisol which is responsible for transference from T4 to active T3.
It is also clinically believed that if the T4 is only measured without total estrogen and only a T4 supplement is given, many times that T4 supplement because of an elevated total estrogen will be converted to a Reverse T3 and cause further signs of a metabolic hypothyroidism.
For further information on metabolic hypothyroidism please go to the articlespage on this website.
With my animal model, I have found that total estrogen clinically appears to deregulate the B and T lymphocytes so that they no longer, perform their individual functions to protect the body but tend to lose sight of self tissue and begin to make anti antibodies which may be the beginning of early aging, autoimmunity and possibly cancer.
Many immune supplements have been designed to stop the deregulated B and T lymphocytes from making anti antibodies to self tissue, however this may also stop their ability to protect the body with their normal functions.
If this happens, there now are two malfunctioning systems in the patient, the endocrine and the immune system.
The real immune deficiency and not just the deregulation that occurs, is with the B lymphocytes production of immunoglobulins (antibodies).
In animals, it appears that the B lymphocyte deficiency pertains to the production of all the immunoglobulins when it occurs but in people there seems to be subpopulations of B lymphocytes that seem to produce immunoglobulins independently when there is an endocrine regulatory imbalance.
An example of this would be the IgA production may be low but the IgM production can be normal along with the IgG production or any other imbalanced combinations may be possible.
In my animal model when the B cell deficiency is present, all immunoglobulins will be deficient.
When the IgA level is deficient, malabsorption will occur through the gut in most patients.
This is particularly noticeable when a patient is hospitalized on parenterals (intravenous, intramuscular and subcutaneous) and when sent home with the same oral medication that was used with the parenterals , the patient becomes ill again.
Because of this result, often a different medication will be prescribed to no avail because of the malabsorption that the deficient IgA has caused.
This is why an IGA level in people and animals should be a standard procedure and included with most general blood tests so that you know as a health care specialist what you have prescribe orally for you patients will be absorbed.
To read more about IgA please go to Townsend Letter, The Importance of IgA, November 1, 2005 Alfred J. Plechner DVM.
Considering the animal model again, the cortisol that is deficient, bound or defective that needs to be replaced in a patient with an IgA deficiency, can only be done through bypassing the gut with a steroid injection.
The length of the effect of the steroid will be determined by the type of steroid that is injected.
To give you an idea about the confusion of the use of an injectable steroid in people, please go to http://www.cwpe.org/node/185.
The injection of the steroid will solve the problem of malabsorption due to a deficient IgA and will fund the negative feedback to the pituitary, reduce the pituitary ACTH which in turn will reduce its excessive effect on the inner layer adrenal cortex and as the estrogen level drops the function of the B and T lymphocytes will return as well as the return of increased levels of immunoglobulins.
When this occurs, if the IgA level is high enough, oral steroids can then be absorbed.
I personally have been involved with human patients with their syndrome and found that with proper hormone supplementation of cortisol, T3, T4, and creating a normalization of the estrogen cortisol ratio.
Now they can create their own immunoglobulins through proper endocrine immune homeostasis with proper hormone supplementation.
Their days of taking monthly blood transfusions are no longer necessary.
If ongoing cortisol replacement is indicated, its use will vary with different species including humans.
Often the medical profession is at a loss as to how to help a patient on long term cortisol therapy without the concern of causing other problems including many side effects.
To maintain a physiological level of replacement regulatory cortisol in a human, usually T3, T4 supplements are indicated to enhance the metabolism of the liver and kidney and allow for proper breakdown and excretion of the cortisol to occur within a 24 hour period otherwise a residue of the steroid may remain which will be added to the next 24 hour dose.
If that steroid residue remains in 24 hours then after a short period of time, the physiological cortisol replacement will become a harmful pharmacological level.
It is reminiscent of what occurred with some of the woman taking estrogen supplementation especially when you remember many of them may have had an ovarian estradiole deficiency but without measuring total estrogen they may have been estrogen prominent and giving them an estrogen supplement caused an estrogenic build up and pushed them into an estrogen dominance causing all kinds of diseases including cancer.
Also, if this thyroid supplementation is not done, usually the physiological dose for cortisol replacement will become a pharmacological dose and cause side effects for the patient.
If a short half life cortisol replacement is used like Cortef, thyroid hormone may not be needed unless the elevated total estrogen is binding the receptor sites of the patient’s thyroid or the patient’s thyroid is malfunctioning.
With the animal model, canines usually require a twice a day dose of T4 only.
Felines usually do not need a thyroid replacement when taking a cortisol replacement unless they are truly hypothyroid.
With equines, 90% of the replacement therapy only needs to be done with thyroid hormones because as part of their overall problem, they may be ingesting hay and food pellets that contain high amounts of phytoestrogens which will bind the cortisol and thyroid hormones.
By increasing the metabolism of the horse’s liver, it seems to help the situation by breaking down the estrogen without using a cortisol replacement.
It is generally believed that different kinds of hormone may be used to fund a cortisol imbalance for people and for animal patients.
It is generally believed that progesterone is turned into prednisolone, which then funds the negative feedback to the pituitary and helps keep the patient normal.
In the animal model, the use of a cortisol replacement itself seems to be all that is needed to fund the negative feedback to the pituitary but with humans other hormones may be tried instead, in hopes of avoiding the actual fear of using an actual steroid.
Pregnenolone and progesterone are examples of this.
But what may not have been realized is that cortisol must go through 5 different enzymatic reactions to be transformed from cholesterol.
When the enzymatic actions cleave the cholesterol, the end product is transformed into pregnenolone.
Once the pregnenolone goes through its enzyme cycle, it is transformed into progesterone.
Once the progesterone goes through its enzymatic transformation, it becomes Prednisolone and is used as cortisol.
I think you can now realize that if there are any imbalances in the enzymatic cycles for these intermediary hormones, pregnenolone and progesterone may never be transformed into cortisol so in a patient with a possible enzyme transformation problem, supplementing pregnenolone and progesterone may prove to be of little value.
I have also noted previously that even though the cortisol level in an animal may be normal, it still can be defective which is easily seen by doing the animal model blood test.
There is even a report in the human literature indicating that a glucocorticoid receptor defect.
To read more, please go to Primary Glucocorticoid Receptor Defect with Likely Familial Involvement.
I have always wondered when cholesterol is transformed into cortisol, if ingested cholesterols from different species of animals and fish might be mal-processed differently by the enzymatic transformation into cortisol.
I thought it might be interesting one day to find a way to radioactively or with some other technique, tag the different kinds of cholesterol and actually find out where they end up in the body in their transformations and if they are active or not or might even be possibly harmful?
Just some of my thoughts!
I apologize for digressing.
It is interesting, while thinking about the health concerns that come with high cholesterol levels and ratio imbalances between HDL and LDL, if it might be time to realize that somewhere in the 5 steps if one or more of the enzymatic reactions are flawed, the production of cortisol may also be flawed or deficient causing the production of elevated total estrogen and the elevated estrogen decreasing the metabolism of the patient by binding the thyroid receptor sites and thereby reducing the rate and transference or break down of cholesterol itself.
This certainly could lead to elevated cholesterol and create all the various diseases that accompany elevated cholesterol.
It also makes you wonder if the total estrogen is elevated and binds the thyroid, then the levels of cholesterol may also remain high because metabolically, it is not being broken down and as already mentioned, it is not being transferred into cortisol for the body to use because of an enzymatic imbalance.
It should start to make you wonder, if lowering your cholesterol may be the wrong answer in certain health situations, because you may be inadvertently lowering your cortisol also.
The medical literature does indicate that there are 5 steps necessary for cholesterol to be turned into active cortisol.
The transformation begins with the cleavage of the side chain of the cholesterol by the enzyme cholesterol desmolase enzyme, cytochrome CYP11A1 (P450scc) to create pregnenolone.
Conversion of pregnenolone to progesterone is accomplished by 3 Beta-hydroxy steroid dehydrogenase with isommerization and successive hydroxylation at the 17 alph, 21 and 11 beta positions.
Each is mediated by a distinct P450 which finally transforms into cortisol.
This may explain from a clinical perspective why some patients which do have the 5 enzymatic steps functioning can do well on pregnenolone or progesterone only, but as mentioned before, while others may need a straight cortisol replacement because their enzymes will not allow then to complete the 5 steps necessary to produce their own cortisol.
More in depth information is available regarding the 5 enzymatic steps necessary to create cortisol from cholesterol by reading Biological Sciences-Medical Sciences- Maria I. New and Robert C. Wilson PNAS-October 26, 1999, vol. 96 no. 22, 12790-12797.
By not using a direct cortisol replacement, an improper enzymatic transformation of cholesterol to cortisol, may still allow for the continued production of a deficient, defective or bound cortisol, an increased in adrenal estrogen that binds the receptor sites of thyroid hormone and with the slowing of the overall metabolism, may still cause elevated levels of cholesterol including a deregulated, deficient immune system that may accompany many of these various syndromes.
As the total estrogen rises, more inflammation of the cells that line all the arteries in the body may occur (endothelial cells), which may lead to strokes, heart attacks and possibly the inflammation that has been is of concern with Alzheimer’s syndrome.
The literature does mention the fact that when many women start their menstrual cycle, they can develop migraine headaches and epileptic seizures.
This is probably occurring because these women are adrenal estrogen prominent and when the ovarian estrogen is added, it will make them estrogen dominant causing inflammation of the endothelial cells that line their cerebral arteries.
To determine the different amounts of estrogen produced by the ovaries and by the inner layer adrenal cortex, a total estrogen level should be taken from a woman that is still ovulating, on the 7th day of her cycle and again later in the cycle when her ovaries are producing their estrogen.
The difference will help identify the two sources of estrogen and their amounts.
Unfortunately most of the laboratories have not taken into consideration that their values may represent a summation of adrenal and ovarian estrogen and not just ovarian estrogen.
I would hope one day, national values would be established for these differences.
Unfortunately total estrogen is usually not done routinely by most medical laboratories.
So far, almost every case of allergy, autoimmunity and cancer in people and animals that I have been involved with, all seem to have a measurable breakdown of this simple animal model referred to as, Plechner's Syndrome.
To read more about Plechner's Syndrome, please go to the Animal Protocolarticle.
To read about a suggested human protocol and important considerations please got to the Human Protocol article.
Last but not least, to obtain significant blood test results, the sample must be handled properly. For definite directions on how to do this, please go to the Lab Info page on this website.
These are just some of my thoughts that I hope will keep you thinking, because who would have thought, cholesterol is the precursor to cortisol.
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