Let’s analyze the data, VA, and NAS statements.  Let’s pick one we have not really talked about much before such as Thyroid Stimulating Hormone (TSH).


“The Agent Orange Act of 1991, Public Law 102-4,105 Stat. 11, directed the Secretary to seek to enter into an agreement with the National Academy of Sciences (NAS) to review and summarize the scientific evidence concerning the association between exposure to herbicides used in support of military operations in the Republic of Vietnam during the Vietnam Era and each disease suspected to be associated with such exposure.  Congress mandated that NAS determine, to the extent possible:


The wording of the below contract statements is nothing short of “Find whatever you want; just make sure it is not to a positive association that the government would then have to pay.”  Remember we are talking about legal terms for government caused mortality and morbidity for Veterans.  Not some; “Do you qualify for some government assistance program?”


(1) Whether there is a statistical association between the suspect diseases and herbicide exposure, taking into account the strength of the scientific evidence and the appropriateness of the methods used to detect the association;


(2) The increased risk of disease among individuals exposed to herbicides during service in the Republic of Vietnam during the Vietnam Era; and


(3) Whether there is a plausible biological mechanism or other evidence of a causal relationship between herbicide exposure and the health outcome.


Section 3 of Public Law 102-4 also required that NAS submit reports on its activities every two years (as measured from the date of the first report) for a ten-year period.


Section 2 of Public Law 102-4, codified in pertinent part at 38 U.S.C. 1116(b) and (c), provides that whenever the Secretary determines, based on sound medical and scientific evidence, that a positive association (i.e. the credible evidence for the association is equal to or outweighs the credible evidence against the association) exists between exposure of humans to an herbicide agent (i.e. a chemical in an herbicide used in support of the United States and allied military operations in the Republic of Vietnam during the Vietnam Era) and a disease, the Secretary will publish regulations establishing presumptive service connection for that disease. If the Secretary determines that a presumption of service connection is not warranted, he is to publish a notice of that determination, including an explanation of the scientific basis for that determination.  The Secretary's determination must be based on consideration of the NAS reports and all other sound medical and scientific information and analysis available to the Secretary.


Section 2 of the Agent Orange Act of 1991 provided that the Secretary's authority and duties under that section would expire 10 years after the first day of the fiscal year in which NAS transmitted its first report to VA.  The first NAS report was transmitted to VA in July 1993, during the fiscal year that began on October 1, 1992.  Accordingly, VA's authority under section 2 of the Agent Orange Act of 1991 expired on September 30, 2002.  In December 2001, however, Congress enacted the Veterans Education and Benefits Expansion Act of 2001, Public Law 107-103.  Section 201 (d) of that Act extended VA's authority under 38 U.S.C. 1116(b)-(d) through September 30, 2015.


Although 38 U.S.C. 1116 does not define "credible," it does instruct the Secretary to "take into consideration whether the results [of any study] are statistically significant, are capable of replication, and withstand peer review.”


No definitions at all exist in this NAS/VA crapshoot that has legal courtroom judge/jury type ramifications.   


The Secretary reviews studies that report a positive relative risk and studies that report a negative relative risk of a particular health outcome.  He then determines whether the weight of evidence supports a finding that there is or is not a positive association between herbicide exposure and the subsequent health outcome.


The Secretary does this by taking into account the statistical significance, capability of replication, and whether that study will withstand peer review.  Because of differences in statistical significance, confidence levels, control for confounding factors, bias, and other pertinent characteristics, some studies are more credible than others.  The Secretary gives weight to more credible studies in evaluating the overall evidence concerning specific health outcomes.


NAS Report ---


Effects on Thyroid Homeostasis -The thyroid gland secretes hormones (T4 and T3) that stimulate metabolism.  Secretion of T4 and T3 is under the control of thyroid -stimulating hormone (TSH), which is secreted by the anterior pituitary gland.  The thyroid also secretes calcitonin, a hormone that controls calcium concentration in the blood and storage of calcium in bones.  Chemical-induced alterations in thyroid homeostasis can adversely affect the development of many organ systems, including the nervous and reproductive systems.


Most adverse effects are caused by lack of thyroid hormone alone rather than by increases in TSH.  TCDD affects the concentrations of thyroid hormones; the effects appear to be species-dependent and may reflect both the dose and the duration of exposure.  TCDD influences the metabolism of thyroid hormones and TSH.  Studies of environmental exposure have emphasized thyroid alterations in prenatal and early childhood development rather than in adults.


NAS reviewed the thyrotoxic potential of herbicides for the first time in Update 2002 and concluded that there was inadequate or insufficient information to determine an association between exposure to herbicides and adverse effects on thyroid homeostasis.


An occupational study measured serum hormone and TCDD concentration in 37 men who had sprayed 2, 4,5-T.  In correlation analysis, TCDD concentrations were inversely related to T3 and TSH.  The association was strongest when historical, but not current, serum TCDD concentrations were considered.  (Johnson et al., 2001).


No relevant environmental studies were published since Update 2002.


A Vietnam-veterans study examined thyroid hormone status in the AFHS cohort.  At each examination, there was a trend toward an increasing concentration of TSH, which was not accompanied by changes in circulating T4 or in the percentage uptake of T3.  Ranch Hand veterans had TSH significantly higher than did the comparison population.  No changes in microsomal or antithyroid antibodies were observed, nor was there any evidence of changes in clinical thyroid disease.  (Pavukera/., 2003).



The above statements by NAS is neither factual nor true, as you will read below – Ranch Hand did test for and did find microsomal antibodies.  In addition, any change in TSH with or without issues in T3 or T4 can be considered a thyroid disorder.


More important we have a found dose response to dioxin in both TSH and the liver enzyme GGT with a finding of antithyroid antibodies that did not demonstrate a dose response but where found. 


I wonder if any of these scientists have ever heard of subclinical hypothyroid and subclinical hyperthyroid.


Now below is the ultimate in NAS/IOM hypocrisy in dealing with the Veterans Herbicide Issues.  The NAS concluded while TSH was increased T3 and T4 were normal, which after reading the transcripts I am not so sure they even knew what in the hell they measured, thereby indicating there was no medical disorder found.


Taken from the NAS publications - Medicare Coverage of Routine Screening for Thyroid Dysfunction (2003)


“THYROID DYSFUNCTION AND ITS DIAGNOSIS The thyroid gland produces and releases into the circulation hormones that influence basal metabolic processes in nearly all body tissues.  Hypothyroidism, the lack of adequate production of thyroid hormones, can result in fatigue, lethargy, cold intolerance, slowed speech and intellectual function, slowed reflexes, hair loss, dry skin, weight gain, and constipation.  Hyperthyroidism, the production of excessive amounts of thyroid hormones, can cause nervousness, anxiety, heart palpitations, rapid pulse, fatigability, tremor, muscle weakness, weight loss with increased appetite, heat intolerance, frequent bowel movements, increased perspiration, and often thyroid gland enlargement (goiter).  Thyroid gland function and hormone synthesis and release are regulated by thyroid stimulating hormone (TSH) that is secreted by the anterior pituitary gland.  Inadequate thyroid gland output leads to high levels of TSH, while excessive thyroid hormone production suppresses production of TSH.  Levels of serum TSH are generally the most sensitive indicator of thyroid gland function: Abnormal levels of TSH are often found even when serum levels of thyroxine, the principal hormone produced by the thyroid gland, are normal.  By convention, abnormal levels of TSH in the presence of normal serum levels of free thyroxine are described as subclinical thyroid dysfunction; abnormal levels of TSH in the presence of abnormal serum levels of free thyroxine are described as overt thyroid dysfunction.  This terminology can be confusing.  Persons with “subclinical” thyroid dysfunction by this biochemical definition may display clear symptoms or signs of thyroid dysfunction while those with biochemically defined “overt” hypothyroidism may show no other evidence of thyroid dysfunction.”


You see for civilians only according to the IOM abnormal levels of TSH are described as a "thyroid dysfunction" – for Veterans with the same confirmed abnormal TSH in direct relationship to the level of the dioxin, TCDD and a measurement of microsomal antibodies it means nothing.  Why? 


Because our own government created this mess of mortality and morbidity of pain and destruction while the contracted IOM ignores their own publications and findings.



NAS determined the lack of data on the association between exposure to the chemicals of interest and adverse effects on thyroid homeostasis, coupled with the lack of exposure information on Vietnam veterans precludes quantification of any possible increase in their risk.


NAS concluded that there is inadequate or insufficient evidence to determine whether an association exists between exposure to herbicides and adverse effects on thyroid homeostasis.


Taking account of the available evidence and NAS' analysis, the Secretary has found that the credible evidence against an association between herbicide exposure and adverse effects on thyroid homeostasis outweighs the credible evidence for such an association, and he has determined that a positive association does not exist.”


Ranch Hand transcript discussion: 


(Bearing in mind these are the folks that are supposed to be doing the world’s gold standard for dioxin, TCDD exposures.  If not for the kids and ladies I would tell you what this is in Military terms = cluster XXXX!


…And he was just trying to discount the findings, saying the trends are not strong, and that there are insufficient data to support a causal relation.  Well, that's not our job anyway.  We're here to demonstrate an association or not.



                        "Discussion of possible mechanisms was vague."  Well, after you present the findings, in a discussion section the idea is to speculate, and that's what we did.  And he didn't like our speculations.

                        So I think your ideas would help us revise the paper.

                        DR. HARRISON: Okay.  Any last comments on this paper?

                        DR. TREWYN: Okay.  Since one reviewer liked it and one didn't, but the editor just rejected the paper.

                        DR. MICHALEK: Yes.

                        DR. TREWYN: You did not re-contact, explaining how you could refute Reviewer #2?

                        DR. MICHALEK: The editor's letter was clear.  He didn't want to hear rebuttal.  We need to start over with a different journal.

                        DR. TREWYN: And--yes.  And that's always an option anyway.

                        DR. HARRISON: Was it a definitive letter?

                        DR. STOTO: Just had kind of a saturation effect--there are just so many epidemiology journals, that--

                        DR. MICHALEK: One referee said we publish too much.


                        DR. HARRISON: Blame us.  Shame, shame, shame.

                        Any other comments before we go on to the next paper?  We're only 15 minutes late now.

                        [No response.]


Ranch Hand Thyroid - Review Results of the Latest Paper


                        DR. HARRISON: Thyroid.  Thyroid.  This paper says there wasn't any thyroid--weren't any thyroid changes, right?

                        DR. MICHALEK: There was no association between thyroid disease and dioxin, but there were associations between thyroid hormones and dioxin.

                        DR. HARRISON: But you didn't measure TSH.

                        DR. MICHALEK: We did measure TSH.  TSH changed with dioxin.  T4 and T3 did not.

                        DR. HARRISON: Okay.

                        DR. MICHALEK: This paper was accepted by the Annals of Epidemiology, and is in press.  It was presented in Barcelona.  I just show it here, because you may not have seen this before.  This is a summary of all of our thyroid data over the entire study, from 1982 through 1997, written under contract with Drs. Schecter and Pavuk at the University of Texas at Dallas.

                        Slide, please.


                        We all know the background.



                        You know the goals.



                        Okay.  We're talking about any veteran who participated in any of the five physical examinations from the baseline to cycle five.  And here is the same dioxin category analysis that we've been using in all of our published papers where we have broken out comparisons in Ranch Hand into these four categories.  And this slide is simply showing that three is some heterogeneity across these categories that the Ranch Hands in the high category are far more likely to be enlisted ground crew than those in the background category, and they're far more likely to be officers.



                        And here are the dioxin levels across categories, in case you didn't know these.

                        In the high category, the median dioxin is 46 parts per trillion, and in the background category on the Ranch Hand side it's 6 parts per trillion, and in the comparison group it's 4 parts per trillion.  And the maximum dose in Viet Nam is about 3,500 ppt.



                        And here is a graphic showing the dioxin levels in the background, low and high categories, compared to the comparisons.



                        And here is the finding of the paper.  If you look at log transformed TSH means by dioxin category, by physical exam year, you'll see a significant trend in many of the exam years with higher TSH means in the high dioxin category.  In spite of the fact, there's been a change in the laboratory method for measuring TSH--here is the Kelsey Siebold data, it was obviously on a different scale form the measurements made at Scripps in 1985 through 1987.  And those were all accommodated in the statistical analysis.



                        In a repeated measures analysis that accommodates all data over all cycles in all participates we see a significant increase in the mean TSH, using a repeated measures linear model.  Accommodating all data, we see this significant increase, whereas the other analyses were cross-sectional in every single physical exam year.



                        And, however, we saw a mean shift.  We didn't see a significant increase in abnormally high TSH levels.  The odds ratios are all increased, but none of them reach significance in any of the examination years in the high Ranch Hand category.



Lets be clear here – the transcripts did not discuss the values found or the p-values of association or cohort delta p values of difference.  We now know that what was considered “not reaching significance of difference” is meaningless in this study since the comparison cohort assumptions were tainted and flawed.  We now know the study because of this flaw missed a two fold increase in cancers much less the other medical issues and disorders in comparison that were at the time considered not significant.





                        And we saw now corresponding pattern with T4--



                        --or T3, which is not shown.  And when we considered diagnosis of hypo- or hyperthyroidism, we saw no significant increase in risk in the Ranch Hand high category.

                        So this is the conclusion.  We found a significant dose response between dioxin and TSH, but not between dioxin and T4 or T3, and no significant increase in the risk of thyroid disease with increased dioxin level.


I wonder if any of these scientists have ever heard of subclinical hypothyroid and subclinical hyperthyroid or other medical issues that correlate with an increase in TSH and the liver enzymes GGT.


                        Thank you very much.

                        DR. HARRISON: Whew.  Neat.  Or fast.

                        DR. STILLS: [Off mike.]  What is the thought behind the increases in TSH?  The link between dioxin exposure and TSH?  Is it--

                        DR. MICHALEK: There are only two thoughts I have.  First, the results are consistent with animal studies that show an increase in TSH with dioxin body burden, perhaps in mice, and that whatever effect is going on is sub-clinical.

                        The same is true in our analysis of liver dataWe found increases in liver enzymes, but no increase in liver disease with increased dioxin--the interpretation being that perhaps a dose is at such a range that no adverse disease endpoint could be detected; yet, measurements on enzymes did detect a mean shift



The remarkable response found was to elevated Gamma Glutamyl Transferase (GGT) liver enzyme.  (It should be noted I could not find a shift in AST or ALT noted in what few transcripts I had access.  This certainly does not mean it did not exist.)  {Readers remember this little fact for later comparisons.}


I think it is obvious no subclinical findings were even considered in liver enzymes or this entire fatally flawed study.  In addition, the combination of findings was never put together - only single ICD codes were considered per finding, which is, obviously ridiculous in medical evaluations.  One test in and by itself is meaningless for the most part in the medical world and seems to only apply to Herbicide Veterans and a specific single endpoint for government exoneration.



                        DR. OSEI: [Off mike.]  Do you have antibodies--?

                        DR. MICHALEK: We measured what are called microsomal antibodies and we found no dose response.



Now remember the NAS said in this very study Ranch Hand did not find microsomal antibodies.  The statement indicates they did find some form of microsomal antibodies since they concluded there was no dose response.  They found in addition to the “dioxin dose response to elevated TSH” additional microsomal antibodies were found but it was disregarded based on the flawed assumption that these antibodies would also demonstrate a remarkable finding to some sort of dose response to either the dioxin level or the increase in TSH.  In addition, no specific antibody was listed.  If it was against Anti-LKM1 then maybe a correlation could be found to autoimmune hepatitis type II or variant of the disorders listed below.  Microsomal antibodies are particularly important, as it seems to tie in with the P450 liver enzymes that direct immunity as well as immunity type responses.  This could certainly tie in to autoimmune disorders as well as the conditions conducive for B and T cell regulation creating cancer conditions.  After all the liver is the blood filter.




What does the presence of these microsomal antibodies conclude in addition to the increased levels of TSH?


Thyroid antimicrosomal antibody; Anti-microsomal antibody; Microsomal antibody


This test is performed to confirm the cause of thyroid problems or other autoimmune disorders. The body produces microsomal antibodies in response to microsomes escaping from damaged thyroid cells. Such autoantibodies are usually present in Hashimoto's thyroiditis. However, they can also be increased in other autoimmune disorders.


A positive test may indicate:

Additional conditions under which the test may be performed:

Now what is one of the major causes of autoimmune hepatitis and some of these others beside hereditary?  You guessed it!  Environmental Toxic Chemicals.



  1. Epidemiology
    1. Much more common in women than in men
  2. Labs
    1. Transaminases Moderately elevated
      1. Alanine Aminotransferase (ALT) 150-1000
      2. Aspartate Aminotransferase (AST) 150-1000
                             B.            Cholestasis Labs elevated
      1. Gamma glutamyl transferase (GGT) elevated
      2. Alkaline Phosphatase
    1. Liver Function Tests abnormal
      1. Albumin depressed
      2. ProTime prolonged
      3. Bilirubin elevated
  1. Diagnosis

                             A.            Exclude other liver disease

    1. Specific Labs (False Negative: 10-20%)
      1. Antinuclear Antibody (ANA)
      2. Smooth Muscle Antibody (SMA)
      3. Anti-LKM antibody
  IV.            Management
    1. See Prevention of Liver Disease Progression
    2. Corticosteroids
      1. Significantly improve survival
     V.            Course

                             A.            Severe progressive liver disease is more typical

                        DR. OSEI: [Off mike] Okay.  How about--antibodies?

                        DR. MICHALEK: That data was not available.  I'm not sure whether we're measuring that in cycle six or not.  I think the answer is no.

                        DR. OSEI: [Off mike] And these are--in T4, what are you looking at?  The number shift between free T4, and just the total T4?

                        DR. MICHALEK: I think we measured both--free and bound.  And that's described in the paper. 



I think we measured??????  What kind of failure study says we think we measured something?


DR. OSEI: Okay.

                        DR. HARRISON: Didn't you measure what's called T-3 uptake?

                        DR. MICHALEK: Yes.

                        DR. HARRISON: Okay.  So and what you then calculated, using the T4 and the T3 uptake was a free thyroxin index--

                        DR. MICHALEK: Yes.

                        DR. HARRISON:  --but you didn't measure free T4.

                        DR. MICHALEK: No.  We measured the free thyroxin index.

                        DR. HARRISON: Okay.

                        DR. MICHALEK: And found no dose response in free thyroxin.

                        DR. HARRISON: This is subtle enoughI'm not sure that that matters a whole lot anyway.

                        Okay.  And it's accepted.  Hey.  Whoo.

                        DR. MICHALEK: Yes.

                        DR. HARRISON: Go, man, go.



                        Before we go on to the next topic--just in case we lose anyone along the way--there was some comment earlier that August would be a bad month to plan a meeting next year.  And the idea was to shift forward to September.  And the only thing else that I wanted to raise was that if we shift from August to September for our second meeting, then we--as Len pointed out--we should switch from October to November for our third meeting, otherwise we'll be killing ourselves….



Subclinical issues:


Measurement of TSH

The pituitary hormone TSH stimulates the thyroid gland to make and release the thyroid hormone.  When thyroid hormone levels decrease, the TSH rises and vice versa.  Measurement of TSH using a sensitive assay is presently the recommended initial screening test when thyroid disease is suspected.  The TSH assay is able to separate hypothyroid and hyperthyroid patients from normal individuals.  A normal TSH excludes primary thyroid disease.  When the TSH is elevated, this suggests hypothyroidism and when suppressed suggests hyperthyroidism.  Rarely the TSH level may be suppressed by drugs (such as corticosteroids) or by severe psychiatric or non-thyroidal illness.  However, such circumstances are extremely rare in the outpatient setting.

When the TSH is abnormal, measurement of thyroxine (T4) or triiodothyronine (T3) are performed to determine the extent of the thyroid abnormality.  An elevated T4 or T3, in association with a low or suppressed TSH, establishes hyperthyroidism.  An elevated TSH in conjunction with a low T4 establishes hypothyroidism.  Since using the TSH assay as a primary test, doctors have identified patients who have an isolated low or high TSH in association with normal T4 and T3 levels.  Although some of these patients will eventually develop overt thyroid disease, it is presently difficult to predict who they will be.  The assessment and management of such patients needs to be individualized.


Thyroid hormones circulate in association with proteins, which bind thyroid hormones.  It is only the free or unbound portion, which we believe to be active at the tissue level.  However, free levels represent less than 1% of the total thyroid hormone levels.  In certain circumstances, such as pregnancy or the birth control pill, the elevated estrogen or female sex hormone, associated with these conditions, raises the level of thyroid hormone binding protein.  The body will compensate by increasing the production of T4 and T3 so that the free level remains normal.  However, such individuals will have a higher total T4 and T3.  Because the free level remains normal, their TSH does not change.  In many circumstances, measurement of the free T4 and free T3 is available and indeed, many laboratories will perform only free T4 and/or free T3 tests.  Alternatively, the T3 resin uptake test can be performed and provides an indirect measurement of the level of thyroid binding protein.  The FT4 index is the total T4 multiplied by the T3 resin uptake and should be proportional to the true free T4 level.  In pregnancy, the total T4 is elevated, the T3 resin decreased and the free T4 index is normal.  The availability of the TSH screening has largely eliminated any confusion caused by changes in thyroid binding proteins, as the TSH will remain normal in these circumstances.


Patients with Hashimoto's thyroiditis have an autoimmune disease.  Thyroid antibodies are blood proteins, which react against certain of the patient's own proteins (called antigens) within the thyroid gland.  In patients with Hashimoto's thyroiditis, high levels of antibodies are usually found and are therefore markers of the autoimmune process.  Low levels of antibodies are sometimes found in older, normal women and do not necessarily indicate clinical disease.  Patients with Graves' hyperthyroidism have circulating thyroid stimulating antibodies which act like TSH and cause the thyroid cells to over-function.



Subclinical Hypothyroidism – by Elaine Moore


Risk Factors in Subclinical Thyroid Disorders

Subclinical hypothyroidism (SH) has causes and symptoms similar to those of overt hypothyroidism.  This article describes SH and explains why it should be treated.

In the early 1970s, when clinical laboratories developed blood tests to measure thyrotropin, which is also called thyroid stimulating hormone or TSH, the term subclinical hypothyroidism (SH) first emerged.  SH refers to elevated TSH levels in patients with normal levels of thyroid hormone, both FT4 and FT3, associated with few or no symptoms of hypothyroidism.  Prior to this time, doctors recognized that some patients with normal thyroid hormone levels had symptoms of hypothyroidism.  These patients were said to have conditions of preclinical myxedema, compensated euthyroidism, preclinical hypothyroidism, or decreased thyroid reserve.

Today, it's accepted that most SH, like most overt hypothyroidism, is caused by autoimmune thyroid disease. Autoimmune hypothyroid disorders include: 1) a chronic condition of lymphocytic thyroiditis called Hashimoto's thyroiditis, which usually is accompanied by goiter; and 2) an atrophic form of thyroiditis called primary myxedema, which usually causes progressive thyroid destruction.

Subclinical hypothyroidism also occurs in patients with infectious, silent, or postpartum thyroiditis, patients on excessive doses of anti-thyroid medications, patients on lithium, and other medications, patients with hypothyroidism who are on inadequate doses of replacement hormone, and patients with diminished thyroid function related to permanent treatment for hyperthyroidism.


Normally, thyroid hormone production is regulated by a system known as the hypothalamic-pituitary-thyroid axis in which the hypothalamus situated at the base of the brain regulates thyroid hormone levels via the pituitary gland.  When the hypothalamus senses that our thyroid hormone levels are too low for our body's needs, it orders the pituitary gland to release TSH.  TSH, in turn, raises thyroid hormone levels by ordering thyroid cells to grow and produce more hormones.  Likewise, when thyroid hormone levels rise, the pituitary stops secreting TSH and TSH levels fall.  Through this mechanism, thyroid hormone levels are under pituitary control.  However, the hypothalamus is savvy enough to know that our needs for hormone vary from day to day and sudden changes happen.  Therefore, it proceeds slowly and orders the pituitary to take it slow.

Although TSH may start rising and become abnormally elevated before thyroid hormone levels fall below the range, it takes at least 6 weeks for serum TSH levels to accurately reflect thyroid status.  Even with this lag, TSH levels are considered the best test to screen for thyroid disease.  Under normal circumstances, an elevated TSH level is the best indicator of thyroid hormone deficiency.

Normally, the pituitary gland secretes TSH in pulses throughout the day, with peak levels produced at night.  The rate of TSH production varies, depending on our general health, diet, exposure to stress, temperature, circadian rhythm, altitude and other needs.  However, if thyroid function begins to decline due to autoimmune, surgical, or ablative destruction of the thyroid gland the, TSH level can reach 1,000 and still fail to induce production of sufficient thyroid hormone.  Then, thyroid hormone levels are no longer maintained by pituitary control.  The body requires exogenous (from outside of the body) thyroid replacement hormone.  Eventually, after thyroid replacement hormone restores the body's levels, pituitary control is reinstated.  Again, the pituitary pitches in to help when the hypothalamus notices thyroid hormone levels starting to rise and fall.  In treated patients, unless interferences from autoimmunity or medications affect the results, TSH levels can again be used to reflect thyroid status.


However, TSH levels can be influenced by other factors.  For instance, when the immune system produces blocking TSH receptor antibodies that contribute to hypothyroidism, the TSH receptors (the cellular signaling system) on thyroid cells recognize these antibodies as if they were TSH.  Consequently, thinking that we have adequate TSH levels in our blood, TSH production slows down and the serum TSH level is falsely decreased.  TSH can also be falsely decreased by medications including dexamethasone and corticosteroids.  TSH levels also rise for a week and then fall in conditions of non-thyroidal illness, including surgery, trauma, or infection.  TSH levels may be falsely elevated by test interferences caused by TSH antibodies, heterophile antibodies, and anti-human antibodies.  It's important to recognize that a low or normal TSH doesn't mean that one can't be hypothyroid and a high TSH doesn't always indicate subclinical hypothyroidism.  An evaluation of signs, symptoms, and thyroid hormone levels is also needed.

Furthermore, a normal TSH level may not be normal or adequate for the individual.  Normally, we all have optimal levels of FT4, and our TSH will vary as it works to keep FT4 stable.  Since the TSH test was implemented its reference or normal range has changed several times with early tests using a range of 10-20 mu/L based on the TSH levels of hospital workers, many with undiagnosed thyroid disorders.  The newer ranges use a better representation of the normal population.  The current recommended reference range for TSH is 0.3-3.0 mu/L.


Over the last three decades, physicians and researchers have debated the significance of SH and questioned the need for treatment.  This is partially because few long-terms studies of SH exist, and considering the early TSH range, there's no way to estimate its true prevalence.  Has the incidence of subclinical hypothyroidism increased since the 70s or have newer, more sensitive TSH tests and changes to the reference range made this appear to be the case?  Furthermore, because symptoms wax and wane in autoimmune disorders, TSH levels might be elevated one month and normal the next.  Patients with roller coaster results may have been told their suspected thyroid condition had resolved and sent home.  Thus, a wait and see approach prevails among some practitioners.

Recent studies have confirmed this notion that patients with both subclinical hypothyroidism and hyperthyroidism can spontaneously recover.  One recent study confirmed that SH could improve or resolve months or years after the initial diagnosis.  According to this study, remission is not related to age, sex, or levels of thyroid peroxidase (TPO) antibodies.  However, levels of blocking TSH receptor antibodies were not measured and they are often the cause of subclinical hypothyroidism.

Unfortunately, treatment is often withheld in SH despite a well-documented list of associated symptoms. These include: elevated lipid levels, cardiac abnormalities, depression, congestive heart failure, latency of motor nerve conduction, increased intraocular pressure, arthralgia, and cognitive changes. For years laboratory workers have noted a high incidence of cardiac events in ER patients with subclinical hypothyroidism but not subclinical hyperthyroidism. A recent study by Walsh, et al. confirmed that subclinical hypothyroidism, but not subclinical hyperthyroidism, is associated with an increase in fatal and nonfatal coronary heart disease.

A more provocative study would be a determination of how many cardiac events occur among patients waiting for their doctors to decide if treatment for SH is needed.


Diez JJ, Iglesias P, Burman KD, Spontaneous normalization of thyrotropin concentrations in patients with subclinical hypothyroidism. J Clin Endocrinol Metab 2005; 90:4124-4127.

Walsh JP, Bremner AP, Bulsara, MK, O'Leary P, Leedman PJ, Feddema P, Michelangeli V, Subclinical thyroid dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005; 165:2467-2472.

Douglas S. Ross, Subclinical Hypothyroidism, chapter 84 in Werner & Ingbar's The Thyroid, A Fundamental and Clinical Text, 8th Edition, Philadelphia: Lippincott Williams & Wilkins, 2000.


Anxiety in Subclinical Thyroid Conditions


Few studies until now have looked at the connection between subclinical thyroid problems and anxiety.  Researchers set out to look at the connection between anxiety and subclinical thyroid dysfunction, grouping patients as subclinically hyperthyroid (TSH lower than 0.1 mU/L), subclinically hypothyroid with (TSH higher than 4.5 mU/L) and euthyroid (normal TSH levels).  A test known as the Beck's Anxiety Inventory (BAI) was given to all patients.


The research showed that both the subclinical hypothyroid and subclinical hyperthyroid groups had significantly higher anxiety scores than euthyroid group, and subclinical thyroid problems increase anxiety in patients -- whether hyperthyroid or hypothyroid.


The researchers indicated that because mood changes, and especially anxiety due to subclinical thyroid problems may affect quality of life significantly, these effects may be enough to warrant treatment.

Mustafa Sait Gonen, et al. "Assessment of Anxiety in Subclinical Thyroid Disorders" Endocr J Vol. 51: 311-315, (2004).




“The American People's Dioxin Report” by:


Dr. Richard Clapp, Boston University School of Public Health
Pat Costner, Greenpeace
Dr. Beverly Paigen, Jackson Laboratories
Dr. Arnold Schecter, University of Texas School of Public Health-Dallas
Dr. Ted Schettler, Physicians for Social Responsibility
Dr. Allen Silverstone, State University of New York Health Science Center
Tom Webster, Boston University School of Public Health


Peer Reviewers:


Dr. Linda Birnbaum, US Environmental Protection Agency
Dr. Mark Cohen, National Oceanographic and Atmospheric Administration
Dr. Barry Commoner, Queens College
Dr. Lynn Goldman, John Hopkins University School of Public Health
Dr. Philip Landrigan, Mt. Sinai School of Medicine
Dr. George Lucier, National Institute for Environmental Health Sciences
Dr. David Ozonoff, Boston University School of Public Health
Dr. David Rall, retired, former Director, National Toxicology Program.


Excerpts from the last report:


Veterans in the 1987 Ranch Hand study exposed to dioxin had lower than normal, but not *statistically significant, uptake of triidothryonine (T3) (Roenger, 1991), and those with higher than normal serum levels of 2,3,7,8-TCDD had slightly above normal, but not *statistically significant, mean levels of thyroid stimulating hormone (TSH) in both the 1987 study and 1992 follow-up (Roenger, 1991; Grubbs, 1995).  Low T3 uptake and high TSH levels are signs of thyroid imbalance.


*We do not know if the findings were statistically significant or not.  Given the 25-year study missed at least, a two-fold increase in cancers from a specific cohort flaw - then we must assume the levels of significance prior to that revelation on all medical disorders are now false.  Until our congress demands a recalculation of all significant data, by an outside firm, as it applies to each medical disorder found or combination of medical disorders then this study is rendered useless in determining significance of value of non-associations.  Since the flaw is on the government’s side any issues found significant will only be a > significance given the nature of the flaw.  However those disorders that were less than <, borderline, or low-end significant would be expected to have a greater association to the level of dioxin and/or increased rate of incidence. 



Now remember the studies have been for the dioxin, TCDD only for the most part.


Being a purist at heart without exclusionary testing which has never been done for various scientific reasons, other toxic chemicals used could certainly have had endocrine causastions.




Here is some quoted information on those chemicals from the Agency for Toxic Substances and Disease Registry.




“Hexachlorobenzene tends to remain in the environment for a long time.  If it is released to the soil, it has a half-life of 3-6 years.  This means that half of the total amount will disappear after 3-6 years, half of the remaining amount will disappear in another 3-6 years, and this process will continue each 3-6 years thereafter.  If it is released to surface waters such as lakes, rivers, and streams, the half-life is 2.7-5.7 years, and if it is released to groundwater, the half-life is 5.3-11.4 years. 


Since Hexachlorobenzene does not dissolve in water very well, most of it will remain in particles on the bottom of lakes, rivers, or streams.  The evaporation of Hexachlorobenzene into the air is not significant under ordinary conditions.  Once in the air, it can be carried over wide geographic areas.  Its half-life in air ranges from 0.63 to 6.28 years. 


Hexachlorobenzene can enter your body when you eat food contaminated with it, when you breathe particles of it in the air, or when it gets on your skin.  After it enters your body, it rapidly spreads through your blood to many tissues in the body, especially to fat.  This probably happens within a few hours.  Based on the results of a survey of this substance in people's tissues, it will remain in your body, especially in fat, for years.


People in Turkey who, over a long time, ate grain that was accidentally contaminated with Hexachlorobenzene suffered from a liver disease called porphyria cutanea tarda.  (Sound familiar to Vietnam Vets?)


The main effect of porphyria is slowed or stopped formation of heme, the oxygen-carrying part of the hemoglobin molecule found in red blood cells and an important chemical in the body.  Porphyria is identified by elevation of heme precursors called porphyrins in the blood, urine, and stool.  This disease can cause red-colored urine, skin sores, change in skin color, arthritis, and problems of the liver, nervous system, and stomach.



Studies using animals show that eating food laced Hexachlorobenzene for a long time can harm the liver, thyroid, and nervous systems.  The studies using animals also show that eating Hexachlorobenzene for months or years can damage bones, kidneys, and blood, and the immune, endocrine (hormone-releasing), and nervous systems. 


Unborn children and young children may be more sensitive to these effects than adults.


Animal studies support the suggestion that young animals exposed to Hexachlorobenzene before and soon after birth are especially sensitive to Hexachlorobenzene.  Effects on the liver, nervous system, and immune function occurred at lower doses in the young developing animals than in adults. 


Animal studies also showed that Hexachlorobenzene has effects on various endocrine organs, including the thyroid gland (hypothyroidism), parathyroid gland (hyperparathyroidism), adrenal gland, and ovaries.  These tissues produce hormones that are important to normal growth and development of the organism.”




“Pentachlorphenol uncouples oxidative phosphorylation processes thus increasing the metabolic rate and causing hyperpyrexia.  Early signs and symptoms are:


Nausea, fatigue, unusual and excessive sweating, and thirst.  Insomnia, oliguria, and loss of body weight (dehydration) may occur in more protracted cases.  Anxiety and restlessness, increased rate and depth of respiration, palpitations, tachycardia, fever, and eventually convulsions and coma may occur in more severe cases.  Laboratory examination may reveal a rise in white blood cells and hypoglycemia.


Some, but not all of the harmful effects associated with exposure to pentachlorophenol are due to impurities present in commercial pentachlorophenol. 


Short exposures to large amounts of pentachlorophenol in the workplace, or through misuse of products that contain it can cause harmful effects on the liver, kidneys, blood, lungs, nervous system, immune system, and gastrointestinal tract.  If large enough amounts enter the body, heat is produced by the cells in the body, causing an increase in body temperature.  The body temperature can increase to dangerous levels, causing injury to various organs, tissues, and even death.  This effect is the result of exposure to pentachlorophenol itself and not the impurities.” 


Long-term exposure to low levels such as those that occur in the workplace can cause damage to the liver, kidneys, blood, and nervous system.  Studies in animals also suggest that the endocrine system and immune system can also be damaged from long-term exposure to low levels of pentachlorophenol.  All of these effects get worse as the level of exposure increases.


The International Agency for Research on Cancer (IARC) has determined that pentachlorophenol is possibly carcinogenic to humans, and the EPA has classified pentachlorophenol as a probable human carcinogen.


The immune systems were suppressed in family members, including children as young as 8 years old, who were exposed to pentachlorophenol while living in log homes.”


Along the DMZ, there were high incidences of what was called “fevers of unknown origin,” especially with our ground troops.  Pentachlorphenol is known to be dangerous through skin contact.  These men would be evacuated with sudden very high fevers and weakness.  No cause was ever established or at least one was never given for these anomalies.  If it had been malaria or viral infections, that would have been discovered from a simple diagnosis.




“Nitrosamines are another type of carcinogenic chemicals that are known to cause cancers and other medical problems.


Exposure to high concentrations of nitrosamines is associated with increased mortality from cancers of the esophagus, oral cavity, and pharynx.  When used in pesticides or herbicides it may cause DNA damage and cell death.”


From “Concerning Pesticides (including dioxin) and Human Pathology”:(12)


“The thing that was most compelling was the dramatic synergy between two unlike chemicals,” said endocrinologist John McLachlan, who led the Tulane University team.


Instead of one plus one equaling two, we found that one plus one equals a thousand-fold.  We expected interactions, but we were surprised they were so strong.


Because they have estrogen-mimic effects, they can alter normal hormones, much more when they are mixed.  Chemicals were weakly estrogenic alone.  However, when two especially endosulfan and dieldrin were paired, the potency rose by 160 to 1600 times, a huge leap that stunned the researchers.


Therefore two important facts, acute and chronic affectation of the nervous system and immune dysfunction induced by pesticides.


Immune dysfunction can induce:


Diminished resistance to infections.


Anomalous answers, auto-antibodies that attack ourselves in a wrong way producing any immune illness like lupus, scleroderma, Sjogren’s, thyroiditis, adrenalitis, rheumatic arthritis, atrophic gastritis, neoplasms, etc.


Statement by Doctor Francisco Rueda (member of the Gulf War Advisory Committee) the author of “Pesticides (including dioxin) and Human Pathology”: (12)


Statement by Doctor Francisco Rueda (member of the Gulf War Advisory Committee) the author of “Pesticides (including dioxin) and Human Pathology”: (12)


“Many patients are suffering the little knowledge that we the doctors possess of these new human illnesses.  When the doctors don't know or we cannot diagnose, we always say: “all is in your mind.”  A serious error that we continue making and patients go out of our consultations with a prescription of psycho-pharmaco.  We, the doctors should know that chemical substances could produce human illnesses just as the microorganisms.  The one that we don't still have analytic or specific morphologic tests, it should not allow us to mistake our diagnoses.  These new human illnesses can be included inside multiple chemical sensitivity and as sub-categories we should must include: Chronic Fatigue Syndrome, Gulf War Illness, Sick Building Syndrome, Huelva Toxic Syndrome, Pesticide Exposure Syndrome and others.


2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and structurally similar halogenated aromatic hydrocarbons cause a broad range of immunologic effects in experimental animals including decreased host resistance to infectious disease and suppressed humoral and cell-mediated immune responses.  In the mouse, TCDD immunotoxicity has been shown to be an aryl hydrocarbon (Ah) receptor-dependent process.  However, despite considerable research, the biochemical and molecular alterations that occur subsequent to Ah receptor activation that lead to altered immune reactivity remain to be elucidated (to make clear and plausible).


In addition to immune suppression, TCDD promotes inflammatory responses.  This effect may result from an upregulation of the production of inflammatory cytokines such as interleukin-1 and tumor necrosis factor.


Nonhuman primates exposed to TCDD show suppressed antibody responses and changes in lymphocyte subsets in the peripheral blood.”


Remember, the Air Forces scientists indicated the same thing in the Ranch Hand report.  In 1990, the Ranch Handers were showing biological symptoms of what they described as a “chronic dose, inflammatory response.”