RE: Hashimoto's Thyroiditis and Glutathione Depletion

[Guest guest]

Hi Rich,

Very interesting information about the development of Hashimoto's

thyroiditis. On down you wrote:

" It thus seems rather straightforward to suggest the hypothesis that

glutathione depletion is responsible for the elevated prevalence of

Hashimoto's thyroiditis in chronic fatigue syndrome. It also seems

reasonable to suggest that if the accumulated damage to the thyroid

gland is not too severe, it may be possible, by building the

glutathione levels back up to normal, to arrest the damage mechanism

and allow the thyroid gland to regenerate. "

bg responds: If you also add lipid replacement therapy to the above

glutathione production (plus detox the liver, etc. with PhosChol --

phosphatidylcholine capsules or IVs and change to a better diet with

healthy oils, etc., then you also repair, rebuild, replace the cells

and repair the membranes. From my own experience and reading, I

believe our bodies start breaking down at many levels, but when the

Master Detoxifier Glutathione goes, we really " bite the dust " I

think.

There's no telling what the above combined therapy will cure/remit.

Even many people with ALS, Alzheimer's, Parkinson's, and even Autism

have shown great improvement on these protocols. Dr. Bock is one who

has turned around some ALS patients, I read. Plus the Haverford

Clinic group, plus Dr. Wm Lee Cowden, plus Dr. Perlmutter, renowned

neurologist -- sure there are many more that deserve some credit

here -- have used this type treatment very effective, some of these

in controlled studies.

Thanks again for your great post.

bg

> Hi, all.

>

> In the past I have speculated that the development of Hashimoto's

> thyroiditis (autoimmune thyroid disease) that is often reported by

> people with chronic fatigue syndrome (PWCs) might be a result of

the

> glutathione depletion that is observed in many PWCs. This could

> also therefore account for the observed hypothyroidism in many

> PWCs. I alluded to this in the latest version of my Suggested

> General Outline for Dealing with Cases of Chronic Fatigue

Syndrome

> (message 66645 on the CFSMExperimental list, and message 16171 on

> the cfs_research list).

>

> I have now found more evidence for this idea in the literature,

and

> I think I can therefore make a stronger case for it now. I think

> that if this proposition is true, it ties the pathogenesis of one

> more observed condition in CFS into the glutathione depletion

> hypothesis, and it may also explain why some PWCs have reported a

> disappearance of antithyroid antibodies (which were formerly

found)

> after glutathione levels have been raised, using ingestion of

> undenatured whey protein, injections of glutathione, or other

means.

>

> First, some background on the basic physiology and biochemistry

> involved: The thyroid gland has the unique job of producing

iodine-

> containing hormones that are used to regulate the metabolic rate

in

> the cells of the body. As part of the reaction process to form

> these hormones, the thyroid must oxidize iodide ions (I-) to form

> molecular iodine (I2). This is done using hydrogen peroxide,

which

> is made on the external surfaces of the cells of the thyroid. The

> actual oxidation of iodide ions occurs outside the thyroid cells,

> and the cells use glutathione to protect their interiors from

> oxidation reactions that would otherwise be caused by hydrogen

> peroxide that leaks back into the cells.

>

> It has been shown that glutathione depletion occurs in many or

most

> cases of CFS. There are now at least two research groups who have

> reported this explicitly (Kennedy et al. of the Dundee group and

> Kurup and Kurup in India), as well as several groups who have

> presented evidence for a state of oxidative stress in PWCs, which

> implies a lack of glutathione activity, and which is at least

> consistent with actual depletion of glutathione itself. In

> addition, there is now considerable clinical experience showing

the

> benefit of building glutathione in many PWCs, starting with the

work

> of Dr. Cheney, which he reported in several public lectures

in

> early 1999, and further including the work of Dr. Salvato

> and most recently the work of Dr. Kane and co-authors of

> The Detoxx Book (www.detoxxbook.com).

>

> It is known that glutathione is compartmentalized in the body,

> meaning that its concentration is normally maintained at different

> levels in the cells of the various organs, and we do not yet have

> evidence for the extent of glutathione depletion that occurs in

the

> thyroid gland specifically in CFS. This will depend on the

overall

> degree of glutathione depletion in the particular PWC, as well as

> the ability of the thyroid to compete with other organs for scarce

> supplies of the amino acids needed to synthesize glutathione, or

for

> the scarce glutathione in the blood stream, or both. This ability

> to compete, in turn, depends on the concentrations of the rate-

> limiting enzymes for synthesizing glutathione or for extracting it

> from the blood, which are gamma glutamylcysteine synthetase and

> gamma glutamyl transpeptidase, respectively. I don't think these

> concentrations are currently known.

>

> If glutathione becomes sufficiently depleted in the thyroid cells,

> it seems clear from the paper by Ekholm and Bjorkman (abstract

shown

> below) that hydrogen peroxide will be able to perform oxidation

> reactions inside the cells. These will include oxidation of

iodide

> ions, leading to iodination of proteins inside the cells, which

> would no doubt be deleterious to the health of the cells. In

> addition, if glutathione is depleted inside the cells of the

> thyroid, it will also be depleted in the extracellular space, and

> the abstract below by Duthoit et al. reports on evidence that

> hydrogen peroxide can cleave thyroglobulin to form a small

> immunoreactive fragment which is then able to enter living

> thyrocytes. This mechanism could therefore serve as the basis for

> more rapid than normal die-off of thyroid cells and the

development

> of the autoimmune thyroid antibodies found in Hashimoto's

> thyroiditis.

>

> It thus seems rather straightforward to suggest the hypothesis

that

> glutathione depletion is responsible for the elevated prevalence

of

> Hashimoto's thyroiditis in chronic fatigue syndrome. It also

seems

> reasonable to suggest that if the accumulated damage to the

thyroid

> gland is not too severe, it may be possible, by building the

> glutathione levels back up to normal, to arrest the damage

mechanism

> and allow the thyroid gland to regenerate.

>

> Some further notes: It is also clear that elevated mercury levels

> are present in many PWCs, and this is also consistent with

> glutathione depletion, since glutathione normally has the

> responsibility for removing mercury from the body. Because of

this,

> careful detoxification of mercury from the body is a prerequisite

to

> restoring the glutathione levels. In some cases, it may be

possible

> to detoxify the mercury solely by building the glutathione

> directly. In other cases, it may be necessary to remove the

mercury

> by chelation in order to be able to build the gluthathione, since

> high levels of mercury have been shown to inhibit enzymes needed

to

> make, recycle and use glutathione. Mercury detoxification must be

> done very carefully in order to avoid moving more of this

neurotoxin

> into the brain and the nervous system. In addition, when building

> glutathione, I think it is important to monitor the cysteine level

> in the blood periodically, to ensure that it does not rise too

high,

> as it is a neurotoxin in its own right, as well as a transporter

of

> mercury into the brain.

>

>

> " Endocrinology. 1997 Jul;138(7):2871-8.

>

> Glutathione peroxidase degrades intracellular hydrogen peroxide

and

> thereby inhibits intracellular protein iodination in thyroid

> epithelium.

>

> Ekholm R, Bjorkman U.

>

> Institute of Anatomy and Cell Biology, Goteborg University, Sweden.

>

> Protein iodination in the thyroid is largely confined to the

surface

> of the epithelium. Intracellular iodine binding is insignificant.

We

> have tested our hypothesis that the key mechanism in the control

of

> intracellular iodination is the control of the intracellular

> availability of H2O2. The sites of iodination were identified by

> locating bound radioiodine in electron microscopic

autoradiographs,

> produced from porcine thyroid epithelium grown on filter in

> Transwell bicameral culture chambers. Autoradiographs obtained

after

> standard incubations with 125I for 15 min to 3 h were all

> characterized by concentrations of autoradiographic grains along

the

> external surface of the plasma membrane and very few grains over

the

> cytoplasm. The presence of 10 microM H2O2 in the incubation medium

> resulted in a drastically changed labeling pattern now showing a

> dissemination of grains over the entire cytoplasm. Epithelia with

> elevated GSH peroxidase activity produced autoradiographs showing

> the same restriction of grains to the cell surface as controls;

this

> pattern was the same in the absence and presence of H2O2 (up to 10

> microM). Cultures with subnormal GSH peroxidase activity presented

> cytoplasmic labeling both in the absence and presence of H2O2. In

> conclusion, iodine binding in filter-cultured thyroid epithelium

> under normal conditions is an extracellular process located at the

> cell surface. When H2O2 is available intracellularly, iodination

> takes place in the cytoplasm, evidently catalyzed by intracellular

> thyroperoxidase. Normally, this iodination is prevented by

cytosolic

> GSH peroxidase that effectively degrades H2O2 and thus controls

> intracellular iodination. The observations should be applicable to

> the thyroid in vivo. "

>

>

>

> " Biochem J. 2001 Dec 15;360(Pt 3):557-62.

>

> Hydrogen peroxide-induced production of a 40 kDa immunoreactive

> thyroglobulin fragment in human thyroid cells: the onset of

thyroid

> autoimmunity?

>

> Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK,

> Feldt-Rasmussen U, Carayon P, Ruf J.

>

> U555 INSERM, Faculte de Medecine Timone, Universite de la

> Mediterranee, Marseille, France.

>

> We recently reported that, during in vitro thyroid-hormone

> synthesis, H(2)O(2) stress cleaved thyroglobulin (Tg) into C-

> terminal peptides. These peptides were found to contain the

> immunodominant region of Tg recognized by Tg autoantibodies from

> patients with an autoimmune thyroid disease. To test the

hypothesis

> that Tg fragmentation is an early upstream initiating event

involved

> in Tg autoimmune response and the consequence of oxidative

injuries,

> we studied the effect of H(2)O(2) stress on human thyroid cells.

In

> culture conditions allowing Tg synthesis and iodine organification

> by the cells, we found that bolus addition of increasing

millimolar

> doses of H(2)O(2) induced a dose-response appearance of floating

> cells in the culture medium. These cells apparently resulted from

a

> necrotic process, and they bore iodinated Tg fragments. These

> fragments were found to be similar to those previously obtained in

> vitro from purified Tg. In both cases, Tg peptides were recognized

> by a well-defined monoclonal antibody directed to the

immunodominant

> region of Tg. The smallest immunoreactive Tg peptide had a

molecular

> mass of 40 kDa and entered human thyrocytes more efficiently than

> the entire Tg. These data suggest that thyrocytes exposed to

locally

> increased H(2)O(2) doses accumulate fragmented Tg for further

> delivery into surrounding living thyrocytes in the course of an

> autoimmune response. "

>

>

> Rich Van Konynenburg, Ph.D.

[Guest guest]

Hi Rich thanx for your excellent summary and articles . I have hashimotoes

thyroiditis and i strongly believe elevated mercury levels but am so toxic

that detoxing is extremely difficult and dangerous. Even though i have been

able to get my immunopro rx up to 2 scoops day from less than a 1/8 tsp

years ago , my hashimotoes has been difficult to treat. ..now i know why.

thanx .tealk

> [Original Message]

> From: rvankonynen <richvank@...>

> < >

> Date: 5/17/2004 2:38:11 PM

> Subject: Hashimoto's Thyroiditis and Glutathione

Depletion

>

> Hi, all.

>

> In the past I have speculated that the development of Hashimoto's

> thyroiditis (autoimmune thyroid disease) that is often reported by

> people with chronic fatigue syndrome (PWCs) might be a result of the

> glutathione depletion that is observed in many PWCs. This could

> also therefore account for the observed hypothyroidism in many

> PWCs. I alluded to this in the latest version of my Suggested

> General Outline for Dealing with Cases of Chronic Fatigue Syndrome

> (message 66645 on the CFSMExperimental list, and message 16171 on

> the cfs_research list).

>

> I have now found more evidence for this idea in the literature, and

> I think I can therefore make a stronger case for it now. I think

> that if this proposition is true, it ties the pathogenesis of one

> more observed condition in CFS into the glutathione depletion

> hypothesis, and it may also explain why some PWCs have reported a

> disappearance of antithyroid antibodies (which were formerly found)

> after glutathione levels have been raised, using ingestion of

> undenatured whey protein, injections of glutathione, or other means.

>

> First, some background on the basic physiology and biochemistry

> involved: The thyroid gland has the unique job of producing iodine-

> containing hormones that are used to regulate the metabolic rate in

> the cells of the body. As part of the reaction process to form

> these hormones, the thyroid must oxidize iodide ions (I-) to form

> molecular iodine (I2). This is done using hydrogen peroxide, which

> is made on the external surfaces of the cells of the thyroid. The

> actual oxidation of iodide ions occurs outside the thyroid cells,

> and the cells use glutathione to protect their interiors from

> oxidation reactions that would otherwise be caused by hydrogen

> peroxide that leaks back into the cells.

>

> It has been shown that glutathione depletion occurs in many or most

> cases of CFS. There are now at least two research groups who have

> reported this explicitly (Kennedy et al. of the Dundee group and

> Kurup and Kurup in India), as well as several groups who have

> presented evidence for a state of oxidative stress in PWCs, which

> implies a lack of glutathione activity, and which is at least

> consistent with actual depletion of glutathione itself. In

> addition, there is now considerable clinical experience showing the

> benefit of building glutathione in many PWCs, starting with the work

> of Dr. Cheney, which he reported in several public lectures in

> early 1999, and further including the work of Dr. Salvato

> and most recently the work of Dr. Kane and co-authors of

> The Detoxx Book (www.detoxxbook.com).

>

> It is known that glutathione is compartmentalized in the body,

> meaning that its concentration is normally maintained at different

> levels in the cells of the various organs, and we do not yet have

> evidence for the extent of glutathione depletion that occurs in the

> thyroid gland specifically in CFS. This will depend on the overall

> degree of glutathione depletion in the particular PWC, as well as

> the ability of the thyroid to compete with other organs for scarce

> supplies of the amino acids needed to synthesize glutathione, or for

> the scarce glutathione in the blood stream, or both. This ability

> to compete, in turn, depends on the concentrations of the rate-

> limiting enzymes for synthesizing glutathione or for extracting it

> from the blood, which are gamma glutamylcysteine synthetase and

> gamma glutamyl transpeptidase, respectively. I don't think these

> concentrations are currently known.

>

> If glutathione becomes sufficiently depleted in the thyroid cells,

> it seems clear from the paper by Ekholm and Bjorkman (abstract shown

> below) that hydrogen peroxide will be able to perform oxidation

> reactions inside the cells. These will include oxidation of iodide

> ions, leading to iodination of proteins inside the cells, which

> would no doubt be deleterious to the health of the cells. In

> addition, if glutathione is depleted inside the cells of the

> thyroid, it will also be depleted in the extracellular space, and

> the abstract below by Duthoit et al. reports on evidence that

> hydrogen peroxide can cleave thyroglobulin to form a small

> immunoreactive fragment which is then able to enter living

> thyrocytes. This mechanism could therefore serve as the basis for

> more rapid than normal die-off of thyroid cells and the development

> of the autoimmune thyroid antibodies found in Hashimoto's

> thyroiditis.

>

> It thus seems rather straightforward to suggest the hypothesis that

> glutathione depletion is responsible for the elevated prevalence of

> Hashimoto's thyroiditis in chronic fatigue syndrome. It also seems

> reasonable to suggest that if the accumulated damage to the thyroid

> gland is not too severe, it may be possible, by building the

> glutathione levels back up to normal, to arrest the damage mechanism

> and allow the thyroid gland to regenerate.

>

> Some further notes: It is also clear that elevated mercury levels

> are present in many PWCs, and this is also consistent with

> glutathione depletion, since glutathione normally has the

> responsibility for removing mercury from the body. Because of this,

> careful detoxification of mercury from the body is a prerequisite to

> restoring the glutathione levels. In some cases, it may be possible

> to detoxify the mercury solely by building the glutathione

> directly. In other cases, it may be necessary to remove the mercury

> by chelation in order to be able to build the gluthathione, since

> high levels of mercury have been shown to inhibit enzymes needed to

> make, recycle and use glutathione. Mercury detoxification must be

> done very carefully in order to avoid moving more of this neurotoxin

> into the brain and the nervous system. In addition, when building

> glutathione, I think it is important to monitor the cysteine level

> in the blood periodically, to ensure that it does not rise too high,

> as it is a neurotoxin in its own right, as well as a transporter of

> mercury into the brain.

>

>

> " Endocrinology. 1997 Jul;138(7):2871-8.

>

> Glutathione peroxidase degrades intracellular hydrogen peroxide and

> thereby inhibits intracellular protein iodination in thyroid

> epithelium.

>

> Ekholm R, Bjorkman U.

>

> Institute of Anatomy and Cell Biology, Goteborg University, Sweden.

>

> Protein iodination in the thyroid is largely confined to the surface

> of the epithelium. Intracellular iodine binding is insignificant. We

> have tested our hypothesis that the key mechanism in the control of

> intracellular iodination is the control of the intracellular

> availability of H2O2. The sites of iodination were identified by

> locating bound radioiodine in electron microscopic autoradiographs,

> produced from porcine thyroid epithelium grown on filter in

> Transwell bicameral culture chambers. Autoradiographs obtained after

> standard incubations with 125I for 15 min to 3 h were all

> characterized by concentrations of autoradiographic grains along the

> external surface of the plasma membrane and very few grains over the

> cytoplasm. The presence of 10 microM H2O2 in the incubation medium

> resulted in a drastically changed labeling pattern now showing a

> dissemination of grains over the entire cytoplasm. Epithelia with

> elevated GSH peroxidase activity produced autoradiographs showing

> the same restriction of grains to the cell surface as controls; this

> pattern was the same in the absence and presence of H2O2 (up to 10

> microM). Cultures with subnormal GSH peroxidase activity presented

> cytoplasmic labeling both in the absence and presence of H2O2. In

> conclusion, iodine binding in filter-cultured thyroid epithelium

> under normal conditions is an extracellular process located at the

> cell surface. When H2O2 is available intracellularly, iodination

> takes place in the cytoplasm, evidently catalyzed by intracellular

> thyroperoxidase. Normally, this iodination is prevented by cytosolic

> GSH peroxidase that effectively degrades H2O2 and thus controls

> intracellular iodination. The observations should be applicable to

> the thyroid in vivo. "

>

>

>

> " Biochem J. 2001 Dec 15;360(Pt 3):557-62.

>

> Hydrogen peroxide-induced production of a 40 kDa immunoreactive

> thyroglobulin fragment in human thyroid cells: the onset of thyroid

> autoimmunity?

>

> Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK,

> Feldt-Rasmussen U, Carayon P, Ruf J.

>

> U555 INSERM, Faculte de Medecine Timone, Universite de la

> Mediterranee, Marseille, France.

>

> We recently reported that, during in vitro thyroid-hormone

> synthesis, H(2)O(2) stress cleaved thyroglobulin (Tg) into C-

> terminal peptides. These peptides were found to contain the

> immunodominant region of Tg recognized by Tg autoantibodies from

> patients with an autoimmune thyroid disease. To test the hypothesis

> that Tg fragmentation is an early upstream initiating event involved

> in Tg autoimmune response and the consequence of oxidative injuries,

> we studied the effect of H(2)O(2) stress on human thyroid cells. In

> culture conditions allowing Tg synthesis and iodine organification

> by the cells, we found that bolus addition of increasing millimolar

> doses of H(2)O(2) induced a dose-response appearance of floating

> cells in the culture medium. These cells apparently resulted from a

> necrotic process, and they bore iodinated Tg fragments. These

> fragments were found to be similar to those previously obtained in

> vitro from purified Tg. In both cases, Tg peptides were recognized

> by a well-defined monoclonal antibody directed to the immunodominant

> region of Tg. The smallest immunoreactive Tg peptide had a molecular

> mass of 40 kDa and entered human thyrocytes more efficiently than

> the entire Tg. These data suggest that thyrocytes exposed to locally

> increased H(2)O(2) doses accumulate fragmented Tg for further

> delivery into surrounding living thyrocytes in the course of an

> autoimmune response. "

>

>

> Rich Van Konynenburg, Ph.D.

>

>

>

>

>

> This list is intended for patients to share personal experiences with

each other, not to give medical advice. If you are interested in any

treatment discussed here, please consult your doctor.

>

[Guest guest]

Hi, bg.

Thanks for the response. I think that what you said makes a lot of

sense. These other parts of the protocol should go a long way

toward helping to rebuild the cells. This is also the treatment

approach that is described in The Detoxx Book, by Kane, et

al.

Rich

> > Hi, all.

> >

> > In the past I have speculated that the development of

Hashimoto's

> > thyroiditis (autoimmune thyroid disease) that is often reported

by

> > people with chronic fatigue syndrome (PWCs) might be a result of

> the

> > glutathione depletion that is observed in many PWCs. This could

> > also therefore account for the observed hypothyroidism in many

> > PWCs. I alluded to this in the latest version of my Suggested

> > General Outline for Dealing with Cases of Chronic Fatigue

> Syndrome

> > (message 66645 on the CFSMExperimental list, and message 16171

on

> > the cfs_research list).

> >

> > I have now found more evidence for this idea in the literature,

> and

> > I think I can therefore make a stronger case for it now. I

think

> > that if this proposition is true, it ties the pathogenesis of

one

> > more observed condition in CFS into the glutathione depletion

> > hypothesis, and it may also explain why some PWCs have reported

a

> > disappearance of antithyroid antibodies (which were formerly

> found)

> > after glutathione levels have been raised, using ingestion of

> > undenatured whey protein, injections of glutathione, or other

> means.

> >

> > First, some background on the basic physiology and biochemistry

> > involved: The thyroid gland has the unique job of producing

> iodine-

> > containing hormones that are used to regulate the metabolic rate

> in

> > the cells of the body. As part of the reaction process to form

> > these hormones, the thyroid must oxidize iodide ions (I-) to

form

> > molecular iodine (I2). This is done using hydrogen peroxide,

> which

> > is made on the external surfaces of the cells of the thyroid.

The

> > actual oxidation of iodide ions occurs outside the thyroid

cells,

> > and the cells use glutathione to protect their interiors from

> > oxidation reactions that would otherwise be caused by hydrogen

> > peroxide that leaks back into the cells.

> >

> > It has been shown that glutathione depletion occurs in many or

> most

> > cases of CFS. There are now at least two research groups who

have

> > reported this explicitly (Kennedy et al. of the Dundee group and

> > Kurup and Kurup in India), as well as several groups who have

> > presented evidence for a state of oxidative stress in PWCs,

which

> > implies a lack of glutathione activity, and which is at least

> > consistent with actual depletion of glutathione itself. In

> > addition, there is now considerable clinical experience showing

> the

> > benefit of building glutathione in many PWCs, starting with the

> work

> > of Dr. Cheney, which he reported in several public lectures

> in

> > early 1999, and further including the work of Dr.

Salvato

> > and most recently the work of Dr. Kane and co-authors

of

> > The Detoxx Book (www.detoxxbook.com).

> >

> > It is known that glutathione is compartmentalized in the body,

> > meaning that its concentration is normally maintained at

different

> > levels in the cells of the various organs, and we do not yet

have

> > evidence for the extent of glutathione depletion that occurs in

> the

> > thyroid gland specifically in CFS. This will depend on the

> overall

> > degree of glutathione depletion in the particular PWC, as well

as

> > the ability of the thyroid to compete with other organs for

scarce

> > supplies of the amino acids needed to synthesize glutathione, or

> for

> > the scarce glutathione in the blood stream, or both. This

ability

> > to compete, in turn, depends on the concentrations of the rate-

> > limiting enzymes for synthesizing glutathione or for extracting

it

> > from the blood, which are gamma glutamylcysteine synthetase and

> > gamma glutamyl transpeptidase, respectively. I don't think

these

> > concentrations are currently known.

> >

> > If glutathione becomes sufficiently depleted in the thyroid

cells,

> > it seems clear from the paper by Ekholm and Bjorkman (abstract

> shown

> > below) that hydrogen peroxide will be able to perform oxidation

> > reactions inside the cells. These will include oxidation of

> iodide

> > ions, leading to iodination of proteins inside the cells, which

> > would no doubt be deleterious to the health of the cells. In

> > addition, if glutathione is depleted inside the cells of the

> > thyroid, it will also be depleted in the extracellular space,

and

> > the abstract below by Duthoit et al. reports on evidence that

> > hydrogen peroxide can cleave thyroglobulin to form a small

> > immunoreactive fragment which is then able to enter living

> > thyrocytes. This mechanism could therefore serve as the basis

for

> > more rapid than normal die-off of thyroid cells and the

> development

> > of the autoimmune thyroid antibodies found in Hashimoto's

> > thyroiditis.

> >

> > It thus seems rather straightforward to suggest the hypothesis

> that

> > glutathione depletion is responsible for the elevated prevalence

> of

> > Hashimoto's thyroiditis in chronic fatigue syndrome. It also

> seems

> > reasonable to suggest that if the accumulated damage to the

> thyroid

> > gland is not too severe, it may be possible, by building the

> > glutathione levels back up to normal, to arrest the damage

> mechanism

> > and allow the thyroid gland to regenerate.

> >

> > Some further notes: It is also clear that elevated mercury

levels

> > are present in many PWCs, and this is also consistent with

> > glutathione depletion, since glutathione normally has the

> > responsibility for removing mercury from the body. Because of

> this,

> > careful detoxification of mercury from the body is a

prerequisite

> to

> > restoring the glutathione levels. In some cases, it may be

> possible

> > to detoxify the mercury solely by building the glutathione

> > directly. In other cases, it may be necessary to remove the

> mercury

> > by chelation in order to be able to build the gluthathione,

since

> > high levels of mercury have been shown to inhibit enzymes needed

> to

> > make, recycle and use glutathione. Mercury detoxification must

be

> > done very carefully in order to avoid moving more of this

> neurotoxin

> > into the brain and the nervous system. In addition, when

building

> > glutathione, I think it is important to monitor the cysteine

level

> > in the blood periodically, to ensure that it does not rise too

> high,

> > as it is a neurotoxin in its own right, as well as a transporter

> of

> > mercury into the brain.

> >

> >

> > " Endocrinology. 1997 Jul;138(7):2871-8.

> >

> > Glutathione peroxidase degrades intracellular hydrogen peroxide

> and

> > thereby inhibits intracellular protein iodination in thyroid

> > epithelium.

> >

> > Ekholm R, Bjorkman U.

> >

> > Institute of Anatomy and Cell Biology, Goteborg University,

Sweden.

> >

> > Protein iodination in the thyroid is largely confined to the

> surface

> > of the epithelium. Intracellular iodine binding is

insignificant.

> We

> > have tested our hypothesis that the key mechanism in the control

> of

> > intracellular iodination is the control of the intracellular

> > availability of H2O2. The sites of iodination were identified by

> > locating bound radioiodine in electron microscopic

> autoradiographs,

> > produced from porcine thyroid epithelium grown on filter in

> > Transwell bicameral culture chambers. Autoradiographs obtained

> after

> > standard incubations with 125I for 15 min to 3 h were all

> > characterized by concentrations of autoradiographic grains along

> the

> > external surface of the plasma membrane and very few grains over

> the

> > cytoplasm. The presence of 10 microM H2O2 in the incubation

medium

> > resulted in a drastically changed labeling pattern now showing a

> > dissemination of grains over the entire cytoplasm. Epithelia

with

> > elevated GSH peroxidase activity produced autoradiographs

showing

> > the same restriction of grains to the cell surface as controls;

> this

> > pattern was the same in the absence and presence of H2O2 (up to

10

> > microM). Cultures with subnormal GSH peroxidase activity

presented

> > cytoplasmic labeling both in the absence and presence of H2O2.

In

> > conclusion, iodine binding in filter-cultured thyroid epithelium

> > under normal conditions is an extracellular process located at

the

> > cell surface. When H2O2 is available intracellularly, iodination

> > takes place in the cytoplasm, evidently catalyzed by

intracellular

> > thyroperoxidase. Normally, this iodination is prevented by

> cytosolic

> > GSH peroxidase that effectively degrades H2O2 and thus controls

> > intracellular iodination. The observations should be applicable

to

> > the thyroid in vivo. "

> >

> >

> >

> > " Biochem J. 2001 Dec 15;360(Pt 3):557-62.

> >

> > Hydrogen peroxide-induced production of a 40 kDa immunoreactive

> > thyroglobulin fragment in human thyroid cells: the onset of

> thyroid

> > autoimmunity?

> >

> > Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK,

> > Feldt-Rasmussen U, Carayon P, Ruf J.

> >

> > U555 INSERM, Faculte de Medecine Timone, Universite de la

> > Mediterranee, Marseille, France.

> >

> > We recently reported that, during in vitro thyroid-hormone

> > synthesis, H(2)O(2) stress cleaved thyroglobulin (Tg) into C-

> > terminal peptides. These peptides were found to contain the

> > immunodominant region of Tg recognized by Tg autoantibodies from

> > patients with an autoimmune thyroid disease. To test the

> hypothesis

> > that Tg fragmentation is an early upstream initiating event

> involved

> > in Tg autoimmune response and the consequence of oxidative

> injuries,

> > we studied the effect of H(2)O(2) stress on human thyroid cells.

> In

> > culture conditions allowing Tg synthesis and iodine

organification

> > by the cells, we found that bolus addition of increasing

> millimolar

> > doses of H(2)O(2) induced a dose-response appearance of floating

> > cells in the culture medium. These cells apparently resulted

from

> a

> > necrotic process, and they bore iodinated Tg fragments. These

> > fragments were found to be similar to those previously obtained

in

> > vitro from purified Tg. In both cases, Tg peptides were

recognized

> > by a well-defined monoclonal antibody directed to the

> immunodominant

> > region of Tg. The smallest immunoreactive Tg peptide had a

> molecular

> > mass of 40 kDa and entered human thyrocytes more efficiently

than

> > the entire Tg. These data suggest that thyrocytes exposed to

> locally

> > increased H(2)O(2) doses accumulate fragmented Tg for further

> > delivery into surrounding living thyrocytes in the course of an

> > autoimmune response. "

> >

> >

> > Rich Van Konynenburg, Ph.D.

[Guest guest]

Hi, tealk.

You're welcome. I'd say that your case fits what I was saying

pretty well. It's a difficult hole to climb out of, but it sounds

like you've been making some headway, at least. I hope that you

will be able to continue to make progress against the mercury and

the glutathione deficit. Have you had, or have you considered

having, I.V. glutathione injections?

Rich

> Hi Rich thanx for your excellent summary and articles . I have

hashimotoes

> thyroiditis and i strongly believe elevated mercury levels but am

so toxic

> that detoxing is extremely difficult and dangerous. Even though i

have been

> able to get my immunopro rx up to 2 scoops day from less than a

1/8 tsp

> years ago , my hashimotoes has been difficult to treat. ..now i

know why.

> thanx .tealk

>

>

> > [Original Message]

> > From: rvankonynen <richvank@a...>

> > < >

> > Date: 5/17/2004 2:38:11 PM

> > Subject: Hashimoto's Thyroiditis and

Glutathione

> Depletion

> >

> > Hi, all.

> >

> > In the past I have speculated that the development of

Hashimoto's

> > thyroiditis (autoimmune thyroid disease) that is often reported

by

> > people with chronic fatigue syndrome (PWCs) might be a result of

the

> > glutathione depletion that is observed in many PWCs. This could

> > also therefore account for the observed hypothyroidism in many

> > PWCs. I alluded to this in the latest version of my Suggested

> > General Outline for Dealing with Cases of Chronic Fatigue

Syndrome

> > (message 66645 on the CFSMExperimental list, and message 16171

on

> > the cfs_research list).

> >

> > I have now found more evidence for this idea in the literature,

and

> > I think I can therefore make a stronger case for it now. I

think

> > that if this proposition is true, it ties the pathogenesis of

one

> > more observed condition in CFS into the glutathione depletion

> > hypothesis, and it may also explain why some PWCs have reported

a

> > disappearance of antithyroid antibodies (which were formerly

found)

> > after glutathione levels have been raised, using ingestion of

> > undenatured whey protein, injections of glutathione, or other

means.

> >

> > First, some background on the basic physiology and biochemistry

> > involved: The thyroid gland has the unique job of producing

iodine-

> > containing hormones that are used to regulate the metabolic rate

in

> > the cells of the body. As part of the reaction process to form

> > these hormones, the thyroid must oxidize iodide ions (I-) to

form

> > molecular iodine (I2). This is done using hydrogen peroxide,

which

> > is made on the external surfaces of the cells of the thyroid.

The

> > actual oxidation of iodide ions occurs outside the thyroid

cells,

> > and the cells use glutathione to protect their interiors from

> > oxidation reactions that would otherwise be caused by hydrogen

> > peroxide that leaks back into the cells.

> >

> > It has been shown that glutathione depletion occurs in many or

most

> > cases of CFS. There are now at least two research groups who

have

> > reported this explicitly (Kennedy et al. of the Dundee group and

> > Kurup and Kurup in India), as well as several groups who have

> > presented evidence for a state of oxidative stress in PWCs,

which

> > implies a lack of glutathione activity, and which is at least

> > consistent with actual depletion of glutathione itself. In

> > addition, there is now considerable clinical experience showing

the

> > benefit of building glutathione in many PWCs, starting with the

work

> > of Dr. Cheney, which he reported in several public lectures

in

> > early 1999, and further including the work of Dr.

Salvato

> > and most recently the work of Dr. Kane and co-authors

of

> > The Detoxx Book (www.detoxxbook.com).

> >

> > It is known that glutathione is compartmentalized in the body,

> > meaning that its concentration is normally maintained at

different

> > levels in the cells of the various organs, and we do not yet

have

> > evidence for the extent of glutathione depletion that occurs in

the

> > thyroid gland specifically in CFS. This will depend on the

overall

> > degree of glutathione depletion in the particular PWC, as well

as

> > the ability of the thyroid to compete with other organs for

scarce

> > supplies of the amino acids needed to synthesize glutathione, or

for

> > the scarce glutathione in the blood stream, or both. This

ability

> > to compete, in turn, depends on the concentrations of the rate-

> > limiting enzymes for synthesizing glutathione or for extracting

it

> > from the blood, which are gamma glutamylcysteine synthetase and

> > gamma glutamyl transpeptidase, respectively. I don't think

these

> > concentrations are currently known.

> >

> > If glutathione becomes sufficiently depleted in the thyroid

cells,

> > it seems clear from the paper by Ekholm and Bjorkman (abstract

shown

> > below) that hydrogen peroxide will be able to perform oxidation

> > reactions inside the cells. These will include oxidation of

iodide

> > ions, leading to iodination of proteins inside the cells, which

> > would no doubt be deleterious to the health of the cells. In

> > addition, if glutathione is depleted inside the cells of the

> > thyroid, it will also be depleted in the extracellular space,

and

> > the abstract below by Duthoit et al. reports on evidence that

> > hydrogen peroxide can cleave thyroglobulin to form a small

> > immunoreactive fragment which is then able to enter living

> > thyrocytes. This mechanism could therefore serve as the basis

for

> > more rapid than normal die-off of thyroid cells and the

development

> > of the autoimmune thyroid antibodies found in Hashimoto's

> > thyroiditis.

> >

> > It thus seems rather straightforward to suggest the hypothesis

that

> > glutathione depletion is responsible for the elevated prevalence

of

> > Hashimoto's thyroiditis in chronic fatigue syndrome. It also

seems

> > reasonable to suggest that if the accumulated damage to the

thyroid

> > gland is not too severe, it may be possible, by building the

> > glutathione levels back up to normal, to arrest the damage

mechanism

> > and allow the thyroid gland to regenerate.

> >

> > Some further notes: It is also clear that elevated mercury

levels

> > are present in many PWCs, and this is also consistent with

> > glutathione depletion, since glutathione normally has the

> > responsibility for removing mercury from the body. Because of

this,

> > careful detoxification of mercury from the body is a

prerequisite to

> > restoring the glutathione levels. In some cases, it may be

possible

> > to detoxify the mercury solely by building the glutathione

> > directly. In other cases, it may be necessary to remove the

mercury

> > by chelation in order to be able to build the gluthathione,

since

> > high levels of mercury have been shown to inhibit enzymes needed

to

> > make, recycle and use glutathione. Mercury detoxification must

be

> > done very carefully in order to avoid moving more of this

neurotoxin

> > into the brain and the nervous system. In addition, when

building

> > glutathione, I think it is important to monitor the cysteine

level

> > in the blood periodically, to ensure that it does not rise too

high,

> > as it is a neurotoxin in its own right, as well as a transporter

of

> > mercury into the brain.

> >

> >

> > " Endocrinology. 1997 Jul;138(7):2871-8.

> >

> > Glutathione peroxidase degrades intracellular hydrogen peroxide

and

> > thereby inhibits intracellular protein iodination in thyroid

> > epithelium.

> >

> > Ekholm R, Bjorkman U.

> >

> > Institute of Anatomy and Cell Biology, Goteborg University,

Sweden.

> >

> > Protein iodination in the thyroid is largely confined to the

surface

> > of the epithelium. Intracellular iodine binding is

insignificant. We

> > have tested our hypothesis that the key mechanism in the control

of

> > intracellular iodination is the control of the intracellular

> > availability of H2O2. The sites of iodination were identified by

> > locating bound radioiodine in electron microscopic

autoradiographs,

> > produced from porcine thyroid epithelium grown on filter in

> > Transwell bicameral culture chambers. Autoradiographs obtained

after

> > standard incubations with 125I for 15 min to 3 h were all

> > characterized by concentrations of autoradiographic grains along

the

> > external surface of the plasma membrane and very few grains over

the

> > cytoplasm. The presence of 10 microM H2O2 in the incubation

medium

> > resulted in a drastically changed labeling pattern now showing a

> > dissemination of grains over the entire cytoplasm. Epithelia

with

> > elevated GSH peroxidase activity produced autoradiographs

showing

> > the same restriction of grains to the cell surface as controls;

this

> > pattern was the same in the absence and presence of H2O2 (up to

10

> > microM). Cultures with subnormal GSH peroxidase activity

presented

> > cytoplasmic labeling both in the absence and presence of H2O2.

In

> > conclusion, iodine binding in filter-cultured thyroid epithelium

> > under normal conditions is an extracellular process located at

the

> > cell surface. When H2O2 is available intracellularly, iodination

> > takes place in the cytoplasm, evidently catalyzed by

intracellular

> > thyroperoxidase. Normally, this iodination is prevented by

cytosolic

> > GSH peroxidase that effectively degrades H2O2 and thus controls

> > intracellular iodination. The observations should be applicable

to

> > the thyroid in vivo. "

> >

> >

> >

> > " Biochem J. 2001 Dec 15;360(Pt 3):557-62.

> >

> > Hydrogen peroxide-induced production of a 40 kDa immunoreactive

> > thyroglobulin fragment in human thyroid cells: the onset of

thyroid

> > autoimmunity?

> >

> > Duthoit C, Estienne V, Giraud A, Durand-Gorde JM, Rasmussen AK,

> > Feldt-Rasmussen U, Carayon P, Ruf J.

> >

> > U555 INSERM, Faculte de Medecine Timone, Universite de la

> > Mediterranee, Marseille, France.

> >

> > We recently reported that, during in vitro thyroid-hormone

> > synthesis, H(2)O(2) stress cleaved thyroglobulin (Tg) into C-

> > terminal peptides. These peptides were found to contain the

> > immunodominant region of Tg recognized by Tg autoantibodies from

> > patients with an autoimmune thyroid disease. To test the

hypothesis

> > that Tg fragmentation is an early upstream initiating event

involved

> > in Tg autoimmune response and the consequence of oxidative

injuries,

> > we studied the effect of H(2)O(2) stress on human thyroid cells.

In

> > culture conditions allowing Tg synthesis and iodine

organification

> > by the cells, we found that bolus addition of increasing

millimolar

> > doses of H(2)O(2) induced a dose-response appearance of floating

> > cells in the culture medium. These cells apparently resulted

from a

> > necrotic process, and they bore iodinated Tg fragments. These

> > fragments were found to be similar to those previously obtained

in

> > vitro from purified Tg. In both cases, Tg peptides were

recognized

> > by a well-defined monoclonal antibody directed to the

immunodominant

> > region of Tg. The smallest immunoreactive Tg peptide had a

molecular

> > mass of 40 kDa and entered human thyrocytes more efficiently

than

> > the entire Tg. These data suggest that thyrocytes exposed to

locally

> > increased H(2)O(2) doses accumulate fragmented Tg for further

> > delivery into surrounding living thyrocytes in the course of an

> > autoimmune response. "

> >

> >

> > Rich Van Konynenburg, Ph.D.

> >

> >

> >

> >

> >

> > This list is intended for patients to share personal experiences

with

> each other, not to give medical advice. If you are interested in

any

> treatment discussed here, please consult your doctor.

> >