Hans
Selye
The unfolding financial debacle
on Wall Street and Main Street is unwittingly subjecting the population
en masse to a physiological stress experiment. We need look no further
than at the work of Canadian endocrinologist Hans Selye to understand
the biologic response most humans are now experiencing. Selye's
work, done primarily at the University of Montreal from the 1940s
through the 1970s, focused on the reaction of the body to stress.
His theory of general adaptation syndrome (GAS) was based on observing
the nearly uniform changes that occurred in mice after exposure
to poisonous chemicals and agents. Selye published over 1700 research
articles and authored 15 monographs and seven books. One article,
a classic paper originally published in Nature
in 1936, described the adaptation
syndrome and the response of the organism to chronic unrelieved
stress.1 That paper, "A Syndrome Produced by Diverse
Nocuous Agents," characterized the reaction to stress, which
develops in three stages, in the following way: an initial physiologic
reaction to the stress, the homeostatic adaptation to ongoing stress,
and, finally, the exhaustive reaction to persistent, unrelieved
stress. The three phases observed by Selye and his co-workers in
numerous experiments remain a cornerstone of understanding adrenal
physiology.
Selye's work found that regardless of the stress, be it chemical
or physical, biologic or psychological, the stress reaction always
had an initial emergency response, then general adaptation, and,
finally, exhaustion ultimately leading to organ failure. The description
by Selye in 1936 of these three phases deserves being retold in
2008:
This
syndrome develops in three stages: during the first stage, 6-48
hours after the initial injury, one observes rapid decrease in
size of the thymus, spleen, lymph glands, and liver; disappearance
of fat tissue; edema formation, especially in the thymus and loose
retroperitoneal connective tissue; accumulation of pleural and
peritoneal transudate; loss of muscular tone; fall of body temperature;
formation of acute erosions in the digestive tract, particularly
in the stomach, small intestine, and appendix; loss of cortical
lipoids and chromaffin substances from the adrenals; and sometimes
hyperemia of the skin, exophthalmos, [and] increased lachrymation
and salivation. In particularly severe cases, focal necrosis of
the liver and dense clouding of the crystalline lens are observed.
In the second stage, beginning 48 hours
after the injury, the adrenals are greatly enlarged but regain their
lipoid granules, while the medullary chromaffin cells show vacuolization;
the edema begins to disappear, numerous basophiles appear in the
pituitary; the thyroid shows a tendency towards hyperplasia (more
marked in the guinea pig); general body growth ceases, and the gonads
become atrophic; in lactating animals, milk secretion stops. It
would seem that the anterior pituitary ceases production of growth
and gonadotrophic hormones and prolactin in favor of increased elaboration
of thyrotrophic and adrenotrophic principles, which may be regarded
as more urgently needed in such emergencies.
If the treatment [noxious agent] be continued with relatively small
doses of the drug or relatively slight injuries, the animals will
build up such resistance that in the later part of the second stage
the appearance and function of their organs returns practically
to normal; but with further continued treatment, after a period
of one to three months (depending on the severity of the damaging
agent), the animals lose their resistance and succumb with symptoms
similar to those seen in the first stage; this phase of exhaustion
being regarded as the third stage of the syndrome.1
Selye's monographs display photographs
of the gross anatomy of the adrenal glands in each of the three
phases of the syndrome. In the first stage, the initial insult,
the adrenal gland appears almost the same as in a non-stressed stage,
but there are minor changes in size and coloration. In the second
stage, with persistent stress, the adrenal balloons in size dramatically,
but the enlargement is tissue hyperplasia (enlargement), not edema.
The final stage of chronic exhaustion due to unrelenting stress
is, perhaps, most eye-opening. The adrenal gland has lost all of
its tone, shrunken to nearly half the size of its normal state,
and appears to be non-functioning. The monograph photographs demonstrate
this same series of events in animals of differing species and with
predictable outcomes based on exposure to ongoing stress. When one
beholds the photographs of Selye's animal experiments, there are
no doubts that his work is correct; the tag line at the conclusion
of most papers that additional research is needed would be inappropriate
here.
The financial crises and natural disasters unfolding in 2008 portend
very serious risk to every individual. Whether the individual's
adrenal response is benign and adapts well or is pathologic and
deteriorates progressively depends on the resiliency of each individual's
adrenal system. As practitioners, we need to understand Selye's
model to be able to prevent stress adaptation from becoming adrenal
exhaustion.
Roger J. Williams
Around the same time period that Selye conducted his first experiments
with stress, a chemist named Roger Williams was initiating his own
experimentation with stress. Williams noticed that organisms deprived
of certain nutritional factors were unable to tolerate stress as
well as nourished organisms. These observations led to Williams'
discovery of the B-vitamin pantothenic acid. Like thiamine's relationship
to beriberi and niacin's relationship to pellagra, pantothenic acid
deficiency caused a nutritional deficiency state. Roger Williams
characterized human pantothenic acid deficiency as an unrecognized
medical condition:
According to the broader view of nutrition,
the following are among the effects of nutritional deficiency
[of pantothenic acid]: (1) decreased growth of young; (2) decreased
reproductive ability; (3) decreased length of life; (4) decreased
stamina; (5) decreased vigor as evidenced by loss of physical
activity and playfulness; (6) decreased food efficiency; (7) impaired
appetite; (8) impaired "body wisdom" with respect to
food choices (deficient animals consume by choice more sugar and
more alcohol then well nourished animals); (9) loss of learning
ability; (10) loss of memory, and probably many other losses.
None of the above effects is associated with any easily recognized
lesions in any specific tissue; yet every one may be important
in the realm of health and well-being. The incidence of such human
nutritional impairments may be high.2
Roger Williams' nutritional work led
to his study of alcoholism. When animals were subject to persistent
stress and were fed a chow deprived in pantothenic acid, most animals
opted to drink the water diluted with alcohol rather than drink
plain water. Similar results were noted with other induced vitamin-deficiency
states. However, Williams' studies argued strongly against the psychological
theories that alcohol consumption stemmed from habit and behavioral
conditioning. The fact that B-vitamins could play a role in modifying
the adaptive response to stress was a fundamental tenet in Williams'
approach to health and disease prevention. He developed the theory
of biochemical individuality, which held that individual organisms
may share nutritional requirements, but the extent of nutritional
need would vary depending on general health, genetics, nutritional
status, and level of stress. Williams would strive to prevent the
development of adrenal exhaustion by supplying higher level of nutrients,
such as pantothenic acid. In the 1960s, Williams collaborated with
associates to form the Clayton Foundation in the Department of Chemistry
at the University of Texas at Austin. In 1966, Williams authored
a short history of the collaborative efforts of the investigators
at the Clayton Foundation. The paper provides a bibliography of
seven hundred studies examining the effects of B-vitamins and other
nutritional factors on physiology. Williams' work provides the basis
for much of the mega-vitamin treatment employed in orthomolecular
and nutritional medicine. That conventional medicine disagrees with
the use of mega-vitamin therapy is evidence that Williams' work
has gone largely unrecognized.
1. Selye H. A syndrome produced by diverse
nocuous agents. Nature. 138: July
4, 1936.
2. Williams RJ. The Clayton Foundation
Biochemical Institute: A Short History. University of Texas
at Austin. 1966. Available at: http://bioinst.cm.utexas.edu/williams/CFBI%20Short%History.htm.
Nenah Sylver on
Hypothyroidism
One of the more gratifying aspects of practicing medicine is the
successful treatment of a previously untreated hypothyroid patient.
The treatment of hypothyroidism is surprisingly easy – a tablet
of dessicated thyroid hormone or synthetic thyroxine is typically
the only treatment needed to reverse this disorder. The problem
with hypothyroidism treatment is not determining the therapy but
establishing the diagnosis. Most patients who need thyroid treatment
do not have abnormal serum thyroid hormone studies, but their clinical
picture fits the profile of underactive thyroid functioning. Whereas
conventional endocrinology draws a line in the sand and permits
the diagnosis of hypothyroidism only when the patient has a lab
test abnormality confirming the disorder, most alternative practitioners
and naturopaths accept the diagnosis of hypothyroidism without such
a lab test.
Nenah Sylver examines hypothyroidism in this issue of the Townsend
Letter. Her article is based on the best-selling book Hypothyroidism:
Type 2 by Mark Starr, MD. Starr differentiates between Type
1 hypothyroidism, which is the classic disorder diagnosed with serum
thyroid testing, and Type 2 hypothyroidism, which cannot be diagnosed
with blood or urine testing. Sylver outlines the theoretical differences
of Type 1 and Type 2 hypothyroidism and devotes the bulk of the
article to understanding Type 2 disorder. Sylver's review of hypothyroidism
reminds us that this disorder may be involved in a great many differing
medical pathologies and conditions. The article emphasizes the fact
that the treatment of undiagnosed hypothyroidism may offer clinical
support, if not symptom resolution, to a diverse group of conditions
from fatigue and depression to atherosclerosis and possibly cancer.
Sylver's article also provides a number of "before" and
"after" photographs; it is difficult to recognize the
same individual after thyroid treatment has been administered.
Alfred Plechner
on Adrenal Dysfunction
Veterinarian Alfred Plechner has been a vocal proponent of the under-diagnosis
of hypoadrenalism and hypothyroidism in animals. He has observed
that reproductive failure in dogs, cats, horses, and other animals
is frequently the direct result of insufficient thyroid and adrenal
hormones. Plechner has observed that excess estrogen aggravates
the deficiency of thyroid and adrenal hormones and interferes with
the fertilization process. Moreover, Plechner has observed that
deficiency of thyroid and adrenal hormones as observed on blood
studies is often accompanied by excess estrogen and decreased immunoglobulins,
especially IgA.
Beyond the obvious implications in treating unfertile animals as
well as dogs and cats debilitated by aging and fatigue, Plechner
makes the case that humans suffer the same age-related hormone deficiencies.
Plechner cites the work of William Jeffries, MD, who used low-dose
cortisol to support fatigue, allergies, and inflammatory disorders.
Plechner writes in this issue that his use of low-dose cortisol
in animals has not led to serious adverse effects typical of high-dose,
long-term steroid therapy.
Also please take a look at Dr. Majid Ali's report on the use of
hormones in treating adrenal dysfunctioning. Ali's work focuses
on the important relationship between hormone levels and oxygen
utilization in adrenal disorders.
Jonathan Collin,
MD
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