Can PSC be caused by hormonal problems?

[Guest guest]

Long story short. I think I know why I have developed all of these

autoimmune conditions. I don't want to sound like a lunatic so I

won't write all about it. I am wondering if anyone has an articles or

evidence that supports a hormone deficiency (specifically cortisol) as

the cause behind autoimmune illnesses.

Don't we have some doctors or something on here? I know that Dave

is a super smart person. Dave, if you read this would you mind

emailing me. :-)

Sorry that I have been so out of touch lately. It's been a horrible 6

months but I am now on the road to getting better.

25 from Nebraska

PBC/PSC/Raynauds/Hypothyroid/Chiari

[Guest guest]

,

's disease is an autoimmune disease with cortisol deficency

's disease is a disorder that occurs when the adrenal glands

do not produce enough of their hormones.

Causes Return to top

The adrenal glands are small hormone-secreting organs located on top

of each kidney. They consist of the outer portion (called the cortex)

and the inner portion (called the medulla).

The cortex produces 3 types of hormones:

The glucocorticoid hormones (such as cortisol) maintain sugar

(glucose) control, decrease (suppress) immune response, and help the

body respond to stress.

The mineralocorticoid hormones (such as aldosterone) regulate sodium

and potassium balance.

The sex hormones, androgens (male) and estrogens (female) affect

sexual development and sex drive.

http://www.nlm.nih.gov/medlineplus/ency/article/000378.htm

The doctors suspect that I have addisons disease because I have

severlly low blood pressure. I am currectly being sent to an

endocrinologist to be evaluated because I have know thyropid disease,

the trouble with my blood pressure and I have begun to have problems

with hypoglycemia.

To the best of my understanding, people with 's disease are

more likely to have other autoimmune disorders but I have not been

able to find anything that says cortisol def cause PSC. I also would

be interesteed in knowing if anyone can make a connection between the

two.

Dawn

>

> Long story short. I think I know why I have developed all of these

> autoimmune conditions. I don't want to sound like a lunatic so I

> won't write all about it. I am wondering if anyone has an articles

or

> evidence that supports a hormone deficiency (specifically cortisol)

as

> the cause behind autoimmune illnesses.

>

> Don't we have some doctors or something on here? I know that Dave

> is a super smart person. Dave, if you read this would you

mind

> emailing me. :-)

>

> Sorry that I have been so out of touch lately. It's been a

horrible 6

> months but I am now on the road to getting better.

>

>

> 25 from Nebraska

> PBC/PSC/Raynauds/Hypothyroid/Chiari

>

[Guest guest]

I have been diagnosed with Cushings Disease, I have a small tumor on my pituatary gland - extremely high cortosol - would this be connected to my PSC? The doctors I have beleive the osteoporosis that I have is a direct result of the high cortosol.

Just putting that out there.

Ray Laird - Thunder Bay ON - PSC 2003.

Use Windows Live Messenger to send messages to your buddies on their mobile phones Find out more on our PC to Mobile website

[Guest guest]

Hi ;

Thanks for your complement about being smart ... but actually I'm

pretty dumb when it comes to understanding autoimmune diseases! As

Dawn already mentioned if you are concerned about cortisol

deficiency, please do get checked for 's disease. I would hate

to add another disease to your long list, but it would be important

to get the cortisol deficiency corrected.

In my searching for clues on the diseases that you have mentioned, I

can only come up with one common thread ... and that's the gene

called CTLA-4. Variants of this gene have been shown to be associated

with hypothyroidism, 's disease (at least in the English

population), and PBC, and variants of this gene may confer resistance

to Raynaud's phenomenon in Sjogren syndrome patients (its possible

that variants might be associated with susceptibility to Raynaud's in

other autoimmune backgrounds?)

_______________________________________

Clin Endocrinol (Oxf). 1997 May;46(5):551-4

A CTLA-4 gene polymorphism is associated with both Graves disease and

autoimmune hypothyroidism.

Kotsa K, PF, Weetman AP

Department of Medicine, University of Sheffield Clinical Sciences

Centre, UK.

OBJECTIVE: The autoimmune thyroid diseases, Graves disease and

autoimmune hypothyroidism, result from a complex interaction between

genetic, environmental and endogenous factors. The genetic loci

conferring susceptibility remain unclear. A recent report has

demonstrated an association between a microsatellite polymorphism of

the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves' disease

in Caucasian patients in the USA. The aim of the present study was to

confirm this association in UK patients and to determine whether this

polymorphism is also associated with autoimmune hypothyroidism.

DESIGN: Analysis of Caucasian patients with autoimmune thyroid

disease from a single clinic, compared to local Caucasian controls.

PATIENTS: We studied 112 patients with Graves' disease, 44 with

autoimmune hypothyroidism and 91 controls. MEASUREMENTS: CTLA-4

microsatellite gene polymorphisms were determined by polymerase chain

reaction amplification of genomic DNA and resolution of the products

on sequencing gels. RESULTS: As in previous studies, 21 alleles of

the CTLA-4 microsatellite region were detected. Allele 106 was

significantly increased in patients with Graves' disease (P = 0.006)

and in those with autoimmune hypothyroidism (P = 0.02) when compared

to controls. There was no significant difference between the groups

in the distribution of the other alleles and no association between

allele 106 and sex, HLA-DR or -DQ specificities or the presence of

ophthalmopathy in the Graves' patients. CONCLUSIONS: These results

confirm that the CTLA-4 gene, or one closely associated with it,

confers susceptibility to Grave's disease but is not specific as the

CTLA-4 106 allele is also associated with autoimmune hypothyroidism.

This association seems to be with autoimmune thyroid disease in

general. PMID: 9231050.

_________________________________________________________________

Clin Endocrinol (Oxf). 1998 Nov;49(5):609-13

A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is

associated with autoimmune 's disease in English patients.

Kemp EH, Ajjan RA, Husebye ES, P, Uibo R, Imrie H, Pearce

SH, PF, Weetman AP

Section of Medicine, Northern General Hospital, University of

Sheffield, UK. e.h.kemp@...

OBJECTIVE: Recent studies have demonstrated an association between a

microsatellite polymorphism of the CTLA-4 gene, specifically a 106

base pair allele, and both Graves' disease and autoimmune

hypothyroidism. The aim of the present study was to determine whether

the same polymorphism of the CTLA-4 gene was associated with

autoimmune 's disease. DESIGN AND PATIENTS: We analysed a

microsatellite polymorphism (variant lengths of a dinucleotide (AT)n

repeat) within exon 3 of the CTLA-4 gene in the following groups: 21

English patients with non-associated 's disease, 18 with

autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy

control subjects; 26 Norwegian patients with non-associated 's

disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17

with APS2 and 100 controls; 3 Finnish patients with non-associated

's disease, 5 with APS2 and 71 controls; 10 Estonian patients

with non-associated 's disease, 2 with APS2 and 45 controls.

MEASUREMENTS: The CTLA-4 microsatellite gene polymorphisms were

determined by polymerase chain reaction amplification of genomic DNA

and resolution of the products on sequencing gels. RESULTS: The

frequency of the 106 base pair allele was significantly increased in

the groups of English patients with either non-associated 's

disease or APS2 (P = 0.02 and 0.04, respectively), when compared to

healthy controls with no clinical evidence or family history of

either 's disease or any other autoimmune disorder. For

Norwegian patients with either non-associated 's disease, APS1

or APS2, there was no association (P = 0.69, 0.62 and 0.97,

respectively). This was also the case for Finnish patients with

either non-associated 's disease or APS2 (P = 0.23 and 0.28,

respectively) and for Estonian patients with either non-associated

's disease or APS2 (P = 0.34 and 0.29, respectively).

CONCLUSIONS: These results indicate that differences exist in the

frequency of the 106 base pair allele in different population groups

and in only the English population was the 106 base pair allele

associated with 's disease. PMID: 10197076.

_________________________________________________________________

Gastroenterology. 2008 Jul 1. [Epub ahead of print]

Primary Biliary Cirrhosis Is Associated With a Genetic Variant in the

3' Flanking Region of the CTLA4 Gene.

Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN

Center for Basic Research in Digestive Diseases, Division of

Gastroenterology and Hepatology, Rochester, Minnesota.

BACKGROUND & AIMS: Genetic variation is invoked as a strong component

underlying primary biliary cirrhosis (PBC) and other autoimmune

disorders. Data suggest that some of this genetic risk is shared,

affecting function of the immune mechanisms controlling self-

tolerance. Cytotoxic T-lymphocyte antigen 4 (CTLA4) encodes a

coinhibitory immunoreceptor that is a key regulator of self-tolerance

with established genetic associations to multiple autoimmune diseases

but conflicting evidence of involvement with PBC. We aimed to perform

a more comprehensive assessment of CTLA4 genetic variation in PBC

using a haplotype-tagging based approach. METHODS: Single nucleotide

polymorphisms (SNPs) were genotyped in 402 PBC patients and 279

controls and evaluated for association with PBC and with

antimitochondrial antibody (AMA) status and prior orthotopic liver

transplantation (OLT) among the PBC patients, both individually and

as inferred haplotypes, using logistic regression. RESULTS: All SNPs

were in Hardy-Weinberg equilibrium. We identified a novel and

relatively strong association between PBC and rs231725, a SNP in the

3' flanking region of CTLA4 located outside of the area previously

investigated in PBC. This SNP tags a common CTLA4 haplotype that

contains a number of functionally implicated autoimmune CTLA4 SNPs,

which was also found to be associated with PBC and to a lesser extent

AMA status and prior OLT. CONCLUSIONS: Our findings suggest that

CTLA4 has an impact on the risk of PBC and possibly plays a role in

influencing AMA development as well as progression to OLT among PBC

patients. Replication in a suitable, independent PBC cohort is

needed. PMID: 18778710.

_________________________________________________________________

Arthritis Rheum. 2006 Aug;54(8):2434-40.

Influence of CTLA4 haplotypes on susceptibility and some

extraglandular manifestations in primary Sjögren's syndrome.

Downie-Doyle S, Bayat N, Rischmueller M, Lester S

Hanson Institute and The Royal Adelaide Hospital, Adelaide, South

Australia, Australia.

OBJECTIVE: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a

key negative regulator of the T cell immune response, and the CTLA4

gene is highly polymorphic. Many positive associations between CTLA4

single-nucleotide polymorphisms (SNPs) and various autoimmune

diseases have been identified. Two CTLA4 SNPs that are important

relative to genetic susceptibility in human autoimmune diseases are

the +49GA polymorphism in exon 1 and the CT60A/G polymorphism in the

3'-untranslated region. Using these 2 polymorphisms as markers, we

investigated possible genetic associations of CTLA4 in Australian

patients with primary Sjögren's syndrome. METHODS: One hundred eleven

Australian Caucasian patients with primary SS and 156 population-

based controls were genotyped for CTLA4 by polymerase chain reaction-

restriction fragment length polymorphism methods, using the

restriction enzymes BseXI (+49G/A) and HpyCh4 IV (CT60). RESULTS: The

CT60 and +49G/A SNPs were in strong linkage disequilibrium, and only

3 haplotypes were observed. Significant differences in the haplotype

frequencies between patients with primary SS and controls (P = 0.032)

were observed, with susceptibility to primary SS associated with both

the +49A;CT60A haplotype and the +49A;CT60G haplotype, whereas the

+49G;CT60G haplotype was protective against primary SS. The

+49A;CT60G haplotype association was predominantly with Ro/La

autoantibody-positive primary SS, and the dose of this haplotype

influenced the severity of daytime sleepiness (P = 0.036). The

+49A;CT60A haplotype appeared to be protective against the

development of Raynaud's phenomenon in patients with primary SS (odds

ratio 0.49, 95% confidence interval 0.27-0.91). CONCLUSION: The CTLA4

+49G/A and CT60 haplotypes are associated with susceptibility to

primary SS and with some extraglandular manifestations of the

disease. PMID: 16869018.

_________________________________________________________________

But that leaves PSC and Chiari unaccounted for. When you say Chiari,

do you mean " Budd-Chiari " syndrome?

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

I am not sure if this is appropriate so please forgive me if it

isn't. There is a book called The Autoimmune Connection by

by Rita Baron-Faust Jill P. Buyon, 2004. That is very informative.

The book discusses disorders that commonly run together. It does not

discuss PSC in any debth but does discuss PBC. I keep the book handy

for when my body is doing strange things. It is written mainly for

women; however.

Dawn

> Hi ;

>

> Thanks for your complement about being smart ... but actually I'm

> pretty dumb when it comes to understanding autoimmune diseases! As

> Dawn already mentioned if you are concerned about cortisol

> deficiency, please do get checked for 's disease. I would

hate

> to add another disease to your long list, but it would be important

> to get the cortisol deficiency corrected.

>

> In my searching for clues on the diseases that you have mentioned,

I

> can only come up with one common thread ... and that's the gene

> called CTLA-4. Variants of this gene have been shown to be

associated

> with hypothyroidism, 's disease (at least in the English

> population), and PBC, and variants of this gene may confer

resistance

> to Raynaud's phenomenon in Sjogren syndrome patients (its possible

> that variants might be associated with susceptibility to Raynaud's

in

> other autoimmune backgrounds?)

> _______________________________________

>

> Clin Endocrinol (Oxf). 1997 May;46(5):551-4

>

> A CTLA-4 gene polymorphism is associated with both Graves disease

and

> autoimmune hypothyroidism.

>

> Kotsa K, PF, Weetman AP

>

> Department of Medicine, University of Sheffield Clinical Sciences

> Centre, UK.

>

> OBJECTIVE: The autoimmune thyroid diseases, Graves disease and

> autoimmune hypothyroidism, result from a complex interaction

between

> genetic, environmental and endogenous factors. The genetic loci

> conferring susceptibility remain unclear. A recent report has

> demonstrated an association between a microsatellite polymorphism

of

> the CTLA-4 gene (allele 106) on chromosome 2q33 and Graves' disease

> in Caucasian patients in the USA. The aim of the present study was

to

> confirm this association in UK patients and to determine whether

this

> polymorphism is also associated with autoimmune hypothyroidism.

> DESIGN: Analysis of Caucasian patients with autoimmune thyroid

> disease from a single clinic, compared to local Caucasian controls.

> PATIENTS: We studied 112 patients with Graves' disease, 44 with

> autoimmune hypothyroidism and 91 controls. MEASUREMENTS: CTLA-4

> microsatellite gene polymorphisms were determined by polymerase

chain

> reaction amplification of genomic DNA and resolution of the

products

> on sequencing gels. RESULTS: As in previous studies, 21 alleles of

> the CTLA-4 microsatellite region were detected. Allele 106 was

> significantly increased in patients with Graves' disease (P =

0.006)

> and in those with autoimmune hypothyroidism (P = 0.02) when

compared

> to controls. There was no significant difference between the groups

> in the distribution of the other alleles and no association between

> allele 106 and sex, HLA-DR or -DQ specificities or the presence of

> ophthalmopathy in the Graves' patients. CONCLUSIONS: These results

> confirm that the CTLA-4 gene, or one closely associated with it,

> confers susceptibility to Grave's disease but is not specific as

the

> CTLA-4 106 allele is also associated with autoimmune

hypothyroidism.

> This association seems to be with autoimmune thyroid disease in

> general. PMID: 9231050.

> _________________________________________________________________

>

> Clin Endocrinol (Oxf). 1998 Nov;49(5):609-13

>

> A cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphism is

> associated with autoimmune 's disease in English patients.

>

> Kemp EH, Ajjan RA, Husebye ES, P, Uibo R, Imrie H, Pearce

> SH, PF, Weetman AP

>

> Section of Medicine, Northern General Hospital, University of

> Sheffield, UK. e.h.kemp@...

>

> OBJECTIVE: Recent studies have demonstrated an association between

a

> microsatellite polymorphism of the CTLA-4 gene, specifically a 106

> base pair allele, and both Graves' disease and autoimmune

> hypothyroidism. The aim of the present study was to determine

whether

> the same polymorphism of the CTLA-4 gene was associated with

> autoimmune 's disease. DESIGN AND PATIENTS: We analysed a

> microsatellite polymorphism (variant lengths of a dinucleotide (AT)

n

> repeat) within exon 3 of the CTLA-4 gene in the following groups:

21

> English patients with non-associated 's disease, 18 with

> autoimmune polyglandular syndrome type 2 (APS2) and 173 healthy

> control subjects; 26 Norwegian patients with non-associated

's

> disease, 9 with autoimmune polyglandular syndrome type 1 (APS1), 17

> with APS2 and 100 controls; 3 Finnish patients with non-associated

> 's disease, 5 with APS2 and 71 controls; 10 Estonian

patients

> with non-associated 's disease, 2 with APS2 and 45 controls.

> MEASUREMENTS: The CTLA-4 microsatellite gene polymorphisms were

> determined by polymerase chain reaction amplification of genomic

DNA

> and resolution of the products on sequencing gels. RESULTS: The

> frequency of the 106 base pair allele was significantly increased

in

> the groups of English patients with either non-associated 's

> disease or APS2 (P = 0.02 and 0.04, respectively), when compared to

> healthy controls with no clinical evidence or family history of

> either 's disease or any other autoimmune disorder. For

> Norwegian patients with either non-associated 's disease,

APS1

> or APS2, there was no association (P = 0.69, 0.62 and 0.97,

> respectively). This was also the case for Finnish patients with

> either non-associated 's disease or APS2 (P = 0.23 and 0.28,

> respectively) and for Estonian patients with either non-associated

> 's disease or APS2 (P = 0.34 and 0.29, respectively).

> CONCLUSIONS: These results indicate that differences exist in the

> frequency of the 106 base pair allele in different population

groups

> and in only the English population was the 106 base pair allele

> associated with 's disease. PMID: 10197076.

> _________________________________________________________________

>

> Gastroenterology. 2008 Jul 1. [Epub ahead of print]

>

> Primary Biliary Cirrhosis Is Associated With a Genetic Variant in

the

> 3' Flanking Region of the CTLA4 Gene.

>

> Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN

>

> Center for Basic Research in Digestive Diseases, Division of

> Gastroenterology and Hepatology, Rochester, Minnesota.

>

> BACKGROUND & AIMS: Genetic variation is invoked as a strong

component

> underlying primary biliary cirrhosis (PBC) and other autoimmune

> disorders. Data suggest that some of this genetic risk is shared,

> affecting function of the immune mechanisms controlling self-

> tolerance. Cytotoxic T-lymphocyte antigen 4 (CTLA4) encodes a

> coinhibitory immunoreceptor that is a key regulator of self-

tolerance

> with established genetic associations to multiple autoimmune

diseases

> but conflicting evidence of involvement with PBC. We aimed to

perform

> a more comprehensive assessment of CTLA4 genetic variation in PBC

> using a haplotype-tagging based approach. METHODS: Single

nucleotide

> polymorphisms (SNPs) were genotyped in 402 PBC patients and 279

> controls and evaluated for association with PBC and with

> antimitochondrial antibody (AMA) status and prior orthotopic liver

> transplantation (OLT) among the PBC patients, both individually and

> as inferred haplotypes, using logistic regression. RESULTS: All

SNPs

> were in Hardy-Weinberg equilibrium. We identified a novel and

> relatively strong association between PBC and rs231725, a SNP in

the

> 3' flanking region of CTLA4 located outside of the area previously

> investigated in PBC. This SNP tags a common CTLA4 haplotype that

> contains a number of functionally implicated autoimmune CTLA4 SNPs,

> which was also found to be associated with PBC and to a lesser

extent

> AMA status and prior OLT. CONCLUSIONS: Our findings suggest that

> CTLA4 has an impact on the risk of PBC and possibly plays a role in

> influencing AMA development as well as progression to OLT among PBC

> patients. Replication in a suitable, independent PBC cohort is

> needed. PMID: 18778710.

> _________________________________________________________________

>

> Arthritis Rheum. 2006 Aug;54(8):2434-40.

>

> Influence of CTLA4 haplotypes on susceptibility and some

> extraglandular manifestations in primary Sjögren's syndrome.

>

> Downie-Doyle S, Bayat N, Rischmueller M, Lester S

>

> Hanson Institute and The Royal Adelaide Hospital, Adelaide, South

> Australia, Australia.

>

> OBJECTIVE: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is

a

> key negative regulator of the T cell immune response, and the CTLA4

> gene is highly polymorphic. Many positive associations between

CTLA4

> single-nucleotide polymorphisms (SNPs) and various autoimmune

> diseases have been identified. Two CTLA4 SNPs that are important

> relative to genetic susceptibility in human autoimmune diseases are

> the +49GA polymorphism in exon 1 and the CT60A/G polymorphism in

the

> 3'-untranslated region. Using these 2 polymorphisms as markers, we

> investigated possible genetic associations of CTLA4 in Australian

> patients with primary Sjögren's syndrome. METHODS: One hundred

eleven

> Australian Caucasian patients with primary SS and 156 population-

> based controls were genotyped for CTLA4 by polymerase chain

reaction-

> restriction fragment length polymorphism methods, using the

> restriction enzymes BseXI (+49G/A) and HpyCh4 IV (CT60). RESULTS:

The

> CT60 and +49G/A SNPs were in strong linkage disequilibrium, and

only

> 3 haplotypes were observed. Significant differences in the

haplotype

> frequencies between patients with primary SS and controls (P =

0.032)

> were observed, with susceptibility to primary SS associated with

both

> the +49A;CT60A haplotype and the +49A;CT60G haplotype, whereas the

> +49G;CT60G haplotype was protective against primary SS. The

> +49A;CT60G haplotype association was predominantly with Ro/La

> autoantibody-positive primary SS, and the dose of this haplotype

> influenced the severity of daytime sleepiness (P = 0.036). The

> +49A;CT60A haplotype appeared to be protective against the

> development of Raynaud's phenomenon in patients with primary SS

(odds

> ratio 0.49, 95% confidence interval 0.27-0.91). CONCLUSION: The

CTLA4

> +49G/A and CT60 haplotypes are associated with susceptibility to

> primary SS and with some extraglandular manifestations of the

> disease. PMID: 16869018.

> _________________________________________________________________

>

> But that leaves PSC and Chiari unaccounted for. When you say

Chiari,

> do you mean " Budd-Chiari " syndrome?

>

> Best regards,

>

> Dave

> (father of (23); PSC 07/03; UC 08/03)

>