Thyroid Hormone and Your Heart

[Guest guest]

Titan Initiates Randomized, Double Blind, Placebo Controlled Phase II

Clinical Study of DITPA In Congestive Heart Failure

Tuesday December 14, 7:01 am ET

http://biz.yahoo.com/prnews/041214/nytu073_1.html

SOUTH SAN FRANCISCO, Calif., Dec. 14 /PRNewswire-FirstCall/ -- Titan

Pharmaceuticals Inc., announced today that the company has initiated a

randomized, double blind, Phase IIb study of DITPA, its novel product in

development for treatment of cardiovascular disease. This study will

evaluate DITPA in the treatment of advanced congestive heart failure (CHF)

associated with low serum thyroid hormone levels. DITPA, or 3

5-diiodothyropropionic acid, is a novel analogue of thyroid hormone selected

for its potential to improve congestive heart failure while avoiding

limitations inherent in the use of current thyroid hormone medications in

patients with cardiovascular disease.

Thyroid hormone is an important regulator of the heart and blood vessels,

and adequate levels of thyroid hormone are essential for proper function of

the cardiovascular system. Thyroid hormone improves the ability of the heart

to fill properly (improves diastolic function), reduces the pressure against

which the heart pumps by relaxing small blood vessels (reduces peripheral

vascular resistance), and improves the efficiency of contraction of the

heart so that a greater amount of blood is pumped per contraction (improved

systolic function).

Researchers have demonstrated that approximately 30% of patients with

advanced (NYHA Class III and IV) congestive heart failure have abnormally

low levels of T3, the active form of thyroid hormone needed by heart cells,

and that low levels of T3 are a strong independent predictor of increased

mortality in CHF patients. It is estimated that approximately 1 million CHF

patients collectively in the U.S. and Europe have low levels of thyroid

hormone (T3). Importantly, these patients generally have normal levels of T4

another form of thyroid hormone which is made by the thyroid gland. As a

result, these patients generally show no symptoms of hypothyroidism,

although the form of thyroid hormone needed by the heart and blood vessels,

T3, is significantly reduced.

The important role of thyroid hormone in maintaining heart and blood vessel

function, and the association of low T3 and increased mortality in CHF

suggest a potential role for DITPA as a thyroid hormone replacement therapy

in CHF. Currently available thyroid hormone medications are generally not

suitable for chronic use in CHF, because they are primarily T4 preparations,

or have too short a half-life, and have the potential to increase heart rate

which is an unwanted side effect in CHF patients.

DITPA is a novel analogue of thyroid hormone (T3), that has demonstrated in

preclinical and preliminary, placebo controlled pilot clinical testing the

ability to improve measures of diastolic function, reduce peripheral

vascular resistance, and improve systolic function, without increasing heart

rate. Such pilot clinical testing in CHF patients over 4 weeks also

demonstrated no significant adverse effects.

Titan's current Phase IIb randomized, placebo controlled study will evaluate

150 patients with NYHA Class III-IV CHF and low serum T3 levels. Patients

will receive either of two doses of DITPA or placebo for six months. The

study will be performed at 35 centers in the U.S. In addition to safety, the

study will evaluate clinical and laboratory parameters related to severity

of CHF, including change in global clinical status, echocardiographic

parameters, BNP levels, exercise testing and quality of life measurements.

" We are pleased to initiate this clinical study of DITPA, an important

milestone in the DITPA development program, " stated Dr. Louis R. Bucalo,

Chairman, President and CEO of Titan.

In addition to evaluating DITPA in CHF patients with low T3 levels, the

Company believes that DITPA may also have potential utility in the treatment

of diastolic dysfunction, and the treatment of patients with left

ventricular dysfunction after myocardial infarction.

Diastolic dysfunction, or failure of the heart to fill adequately, is the

primary cause of cardiac dysfunction in approximately 25 percent of the

estimated 8 million people in the US and Europe with CHF. In diastolic

dysfunction, the heart takes longer to relax after each contraction, causing

difficulty in filling the heart fully with blood. Preclinical research

studies indicate that thyroid hormone and DITPA can shorten diastolic

filling time, potentially improving diastolic function.

Left ventricular dysfunction after myocardial infarction is characterized by

subsequent extension of the area of infarction, hypertrophy of the surviving

heart muscle without increase in its blood supply leading to inadequate

heart muscle perfusion, and gradual replacement of heart muscle cells with

fibrosis, a process called pathological ventricular remodeling. Worsening of

CHF due to subsequent infarct expansion, and pathologic ventricular

hypertrophy and remodeling is a major cause of morbidity and mortality in

patients with CHF.

Thyroid hormone is known to promote growth of small blood vessels in the

heart, and has also been demonstrated in animal models to convert pathologic

hypertrophy to more adequately perfused heart muscle. Recent preclinical

studies demonstrate that DITPA also stimulates coronary small blood vessel

growth after myocardial infarction, and reduced extension of infarct size by

approximately 80 percent. In these studies, DITPA was also shown to reduce

ventricular remodeling subsequent to myocardial infarction, and improve

heart function.

Additional support for evaluation of DITPA in this setting is the finding

that thyroid hormone levels decrease in patients after myocardial infarction

and the extent of the decrease correlates with long term outcome.

Specifically, patients whose thyroid hormone levels remain below normal in

the weeks following myocardial infarction have a significantly increased

mortality two years after myocardial infarction.

Based on these and other research studies, the Company may pursue approaches

to evaluation of DITPA in these additional clinical settings.

DITPA is also currently being evaluated in a second randomized, double blind

placebo controlled Phase II study in 150 patients with NYHA Class II-IV CHF

sponsored by the Department of Veterans Affairs ative Studies Program

and funded by a $3.8 million grant.

About Titan Pharmaceuticals

Titan Pharmaceuticals, Inc. (Amex: TTP - News) is a biopharmaceutical

company focused on the development and commercialization of novel treatments

for central nervous system disorders, cancer and cardiovascular disease.

Titan's products in development utilize novel technologies that have the

potential to significantly improve the treatment of these diseases. Titan

also establishes partnerships with government institutions and other leading

pharmaceutical development companies. For more information, please visit the

Company's website at http://www.titanpharm.com .

The press release may contain " forward-looking statements " within the

meaning of Section 27A of the Securities Act of 1933 and Section 21E of the

Securities Exchange Act of 1934. Such statements include, but are not

limited to, any statements relating to the Company's development program and

any other statements that are not historical facts. Such statements involve

risks and uncertainties, including, but not limited to, those risks and

uncertainties relating to difficulties or delays in development, testing,

regulatory approval, production and marketing of the Company's drug

candidates, unexpected adverse side effects or inadequate therapeutic

efficacy of the Company's drug candidates that could slow or prevent product

development or commercialization, the uncertainty of patent protection for

the Company's intellectual property or trade secrets and the Company's

ability to obtain additional financing if necessary. Such statements are

based on management's current expectations, but actual results may differ

materially due to various factors, including those risks and uncertainties

mentioned or referred to in this press release.

Source: Titan Pharmaceuticals Inc.

http://biz.yahoo.com/prnews/041214/nytu073_1.html

Thyroid-Adrenal Connection: Information and Resources

http://www.bestweb.net/~om/thyroid

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Click on http://lbrionline.com/holiday/

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[Guest guest]

I hate to tell them but I am living proof that Armour works to correct this

problem too, just have to adjust it up very slowly. Most likely the swelling I

had that settled in my chest and abdomen at night was setting me up for CHF. I

believe I was in the beginning stages of it when I stopped taking Synthroid and

started my journey with Armour. I have always had conversion problems when on a

T4 only med and THE article confirms that my worst fears about what was

happening to me were indeed a fact.

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

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[Guest guest]

In a message dated 12/15/2004 1:55:31 AM Eastern Standard Time,

artisticgroom@... writes:

> I hate to tell them but I am living proof that Armour works to correct this

> problem too, just have to adjust it up very slowly. Most likely the swelling

> I had that settled in my chest and abdomen at night was setting me up for

> CHF

Val, me too.

I have had all the symptoms of left side heart failure. But with Armour,

these symptoms are slowly improving.

btw, my Dad died of congestive heart failure...i have often wondered if both

my mom AND he had thyroid problems.

cindi

[Guest guest]

In a message dated 12/15/2004 7:37:43 AM Eastern Standard Time,

artisticgroom@... writes:

> Why not test for and TREAT the low T3 in these patients BEFORE it becomes

> CHF??? This almost makes me mad! When are they going to realize that low T3

> and general low thyroid function IS a life threatening condition

yes. i'm mad. failure to properly diagnose has cost me so much in terms of

my health and quality of life for the last two decades. And it wasn't like I

wasn't at the doctor's office several times a year...I was...often....and they

NEVER mentioned thyroid function. I did. Even told them it was in the

family. And they just looked at me and said " normal " . i do hate that word.

cindi

[Guest guest]

In a message dated 12/15/2004 8:20:03 AM Eastern Standard Time,

artisticgroom@... writes:

> Trouble is till more doctors start testing Free T3 how many people will

> die? I wonder how this low T3 was discovered anyway? Seems to me SOMEONE was

> aware of a thyroid problem involved in CHF

Val...I'm thinking that in a lot of disease states...the T3 gets low. In

illness, they KNOW that thyroid function goes down. Like after illness or

surgery...this is already a known fact. And so they often just monitor it. It

seems they got to start figuring out that if the illness is CHRONIC, the T3 may

be

a problem.

For example, my daughter has a kidney disease...and on that forum, they talk

about low thyroid being a problem for PKD patients. And I'm like DUH, the

body is under stress...a chronic illness....and they stop converting well.

Are we the only smart ones?

Cindi

[Guest guest]

In a message dated 12/15/2004 9:43:49 AM Eastern Standard Time,

artisticgroom@... writes:

> What about the disease states that are caused by low T3??? This is what I

> am wondering about. I wonder how much heart failure could be prevented by

> thyroid treatment for a person with borderline or " normal " tests.

>

Oh Val...i think it's just like so much we've discovered that is caused by

hypo...that YES, a heck of a lot of it could be prevented. I think there's a

whole bunch of folks who have had heart attacks because of undiagnosed

hypo...and then DUH, they continue to have low T3 after the heart attack.

Surprise.

Cindi

[Guest guest]

In a message dated 12/15/2004 11:36:16 AM Eastern Standard Time,

klb58@... writes:

> I have noticed that since my two surgeries in the past couple of years

> (emergency gall bladder surgery, tonsilectomy-2nd time, and deviated septum

> fixed) that my thyroid gave me tons of trouble

Kerry,

I too have had some surgeries in the recent years...and I too know that

because I was already having some thyroid problems...that the surgeries just

really

intensified it...moreso than other folks would experience. I can remember

going back to the doctor after one surgery and while waiting in the waiting

room...being so weak...and thinking " I'm gonna faint " ...and staggering to a

nurse

telling her I had to lay down. I just had a really hard time healing and

recovering because of the low thyroid.

cindi

[Guest guest]

In a message dated 12/15/2004 11:36:16 AM Eastern Standard Time,

klb58@... writes:

> tonsilectomy-2nd time

how do you have this a 2nd time?

cindi

[Guest guest]

You know what I have to wonder? Why not test for and TREAT the low T3 in these

patients BEFORE it becomes CHF??? This almost makes me mad! When are they going

to realize that low T3 and general low thyroid function IS a life threatening

condition? It certainly was for me after years of undertreatment with Synthroid.

I would be curious to see how many of the people with CHF and low T3 have been

on Synthroid for how many years. I would bet alot of them.

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

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[Guest guest]

Trouble is till more doctors start testing Free T3 how many people will die? I

wonder how this low T3 was discovered anyway? Seems to me SOMEONE was aware of a

thyroid problem involved in CHF.

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

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Outgoing mail is certified Virus Free.

Checked by AVG anti-virus system (http://www.grisoft.com).

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[Guest guest]

>>I'm thinking that in a lot of disease states...the T3 gets low. <<

What about the disease states that are caused by low T3??? This is what I am

wondering about. I wonder how much heart failure could be prevented by thyroid

treatment for a person with borderline or " normal " tests.

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

---

Outgoing mail is certified Virus Free.

Checked by AVG anti-virus system (http://www.grisoft.com).

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[Guest guest]

In a message dated 12/15/2004 3:01:26 PM Eastern Standard Time,

klb58@... writes:

> and they wonder why heart disease has become a higher killer of women

i'm having a problem trying to decide if they're really that stupid - or it's

just some major conspiracy to hide that fact that some dried pig thyroid

cures a whole bunch of things.

cindi

[Guest guest]

In a message dated 12/15/2004 3:19:05 PM Eastern Standard Time,

artisticgroom@... writes:

> We could all take them to our docs and when they go HMMM give em a swat, or

> when they say it's not your thyroid, must be something else, they get 10

> swats.

>

>

what do they get when they look at your suppressed TSH and say " you're

hyper " ?

cindi

[Guest guest]

In a message dated 12/15/2004 4:03:32 PM Eastern Standard Time,

artisticgroom@... writes:

> My BUTT in their face as I walk out the door!

>

rofl...i thought it would be something like that.

cindi

[Guest guest]

I've wondered about my dad too. He had heart problems, and Alzheimers and a host

of other ailments that very well could have been thyroid related. Too late to

tell from him though. My mom has never had any symptoms of thyroid problems,

although my aunt, her sister, has them. I think my oldest sister has problems

too. She was to check with her doctor at her next apt., but we aren't currently

speaking, so I've no clue if she did or not. I suppose I could send her an

e-mail and ask her. It would be an easy topic to break the ice with.

I have a minor heart problem. Nothing anyone is concerned about. But I wonder if

it would improve if I was optimally treated.

With my t3 being low, I am more concerned now that I read this, than I was

before. But I don't know if my doctor would be as concerned. I may print that

article though for her. Just to show that my low t3 should be optimized. My low

t4 should be up'd too. but....

Cris

Re: Thyroid Hormone and Your Heart

In a message dated 12/15/2004 1:55:31 AM Eastern Standard Time,

artisticgroom@... writes:

> I hate to tell them but I am living proof that Armour works to correct this

> problem too, just have to adjust it up very slowly. Most likely the swelling

> I had that settled in my chest and abdomen at night was setting me up for

> CHF

Val, me too.

I have had all the symptoms of left side heart failure. But with Armour,

these symptoms are slowly improving.

btw, my Dad died of congestive heart failure...i have often wondered if both

my mom AND he had thyroid problems.

cindi

[Guest guest]

In a message dated 12/15/2004 4:07:03 PM Eastern Standard Time,

artisticgroom@... writes:

> You know I was told MANY years ago by the DO that first prescribed Armour

> for me that they would never " find " a cure for cancer cause they were too busy

> making money off it.

i have come to believe this too. but yes, that doc was rather insightful

that many years ago.

cindi

[Guest guest]

In a message dated 12/15/2004 5:37:52 PM Eastern Standard Time,

klb58@... writes:

> when the first doc didn't get them all..they grew back

well good lordy...this is the first i've heard of that.

cindi

[Guest guest]

>>someone needs to smack these docs up the side of the head with a giantic

replica of the thyroid gland...LOL<<

What a great publicity idea! I wonder if a plastics company could be persuaded

to make a fly swatter in the shape of a thyroid gland.. We could all take them

to our docs and when they go HMMM give em a swat, or when they say it's not your

thyroid, must be something else, they get 10 swats.

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

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Outgoing mail is certified Virus Free.

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[Guest guest]

>>what do they get when they look at your suppressed TSH and say " you're

hyper " ? <<

My BUTT in their face as I walk out the door!

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

---

Outgoing mail is certified Virus Free.

Checked by AVG anti-virus system (http://www.grisoft.com).

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[Guest guest]

>>i'm having a problem trying to decide if they're really that stupid - or it's

just some major conspiracy to hide that fact that some dried pig thyroid

cures a whole bunch of things.<<

You know I was told MANY years ago by the DO that first prescribed Armour for me

that they would never " find " a cure for cancer cause they were too busy making

money off it. I think he had some great insight for a doctor of his time.. This

was about 29 years ago.

*Artistic Grooming * Hurricane, WV

Fat cat? Diabetes? Listowner for overweight or hypothyroid cats

http://groups.yahoo.com/group/hypokitties/

---

Outgoing mail is certified Virus Free.

Checked by AVG anti-virus system (http://www.grisoft.com).

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[Guest guest]

hahahaha, I've got a wonderful mental picture of that <lol>

Lynda

Re: Thyroid Hormone and Your Heart

My BUTT in their face as I walk out the door!

*Artistic Grooming * Hurricane, WV

[Guest guest]

After seeing the first hospital bill of my brothers from his heart

attack, I'm sure they are thinking in terms of 'down the road'

finances. Let's face it, if people don't have heart attacks, they

don't need near as many dr's to do bypass surgery as my brother just

had, nor do they need as many nurses for the ICU units, or hospital

rooms, and on and on.

I think they are covering their butts for future revenue to be real

honest. Same with cancer.

SandyE~Houston

On Wed, 15 Dec 2004 15:41:14 EST

nc2406@... wrote:

> In a message dated 12/15/2004 3:01:26 PM Eastern Standard Time,

> klb58@... writes:

>

> > and they wonder why heart disease has become a higher killer of

>women

>

> i'm having a problem trying to decide if they're really that stupid

>- or it's

> just some major conspiracy to hide that fact that some dried pig

>thyroid

> cures a whole bunch of things.

> cindi

>

>

>

[Guest guest]

In a message dated 12/15/2004 10:27:31 PM Eastern Standard Time,

klb58@... writes:

> no dairy at all, *sigh*, said it promoted phlegm..ugh

well they obviously didn't know that back in 1959 when I had my tonsils

out...they gave me lots of ice cream.

cindi

[Guest guest]

Can you tell me what happened with your gallbladder? I had horendous pains 2

weeks ago, and a friend told me she thought it was a gallbladder attack. The

pains went away. So she figured I passed some sort of stone. I'm curious about

where your pains were and what your symptoms were. You can send me an e-mail off

list.

Cris

Re: Thyroid Hormone and Your Heart

I have noticed that since my two surgeries in the past couple of years

(emergency gall bladder surgery, tonsilectomy-2nd time, and deviated septum

fixed) that my thyroid gave me tons of trouble. However, the endo kept me on

Synthroid, only increased it a bit. Makes me really mad to think that he didn't

even test my Free T3..sheesh.....grrrrrr....

Kerry