Re: peripheral vs. general thyroid hormone resistance

[Guest guest]

I need help in making sense of the information below (from Dr. Lowe's site). I'm

trying to understand this...want to make sure you all get out of this what I'm

getting. Here's my understanding (put very simplistically)

Peripheral tissues are include any of the tissues (other than the pituitary)

that are resistant to thyroid hormones. So since the pituitary is getting enough

hormone, then someone with this problem would need more thyroid hormone. This

suppresses TSH...it will show in hyper range...but the peripheral tissues are

not getting enough thyroid hormone...thus peripheral resistance.

Is this how you all understand it?

My neurologist kept trying to explain to me what he felt was happening and I

could never understand it. I think I finally do. He kept telling me he didn't

think my brain cells were getting enough thyroid hormone, and that even though

my TSH showed that I was in the hyper range, he felt I was undermedicated.

So my brain cells would be peripheral tissues.

The nurse practitioner I saw today was telling me it didn't matter that my TSH

was so low because I don't have symptoms of being over-medicated; my symptoms

are still hypo symptoms. I don't remember a thing she said except that you can

have a low TSH like mine, and it may LOOK like hyperthyroidism, but it's not. I

was foggy and just don't remember what she said.

Anyway, how uncanny you posted this article tonight...just as I was reading

this.

Questions, Comments, Opinions WANTED....Thanks, Sheila

December 1, 1997

Question: I'm confused by the term " thyroid hormone resistance, " which you

invoke at the cellular level to explain why supraphysiologic levels of thyroid

hormones are required to alleviate symptoms in some patients. My impression is

that you've totally suppressed the TSH levels (TSH < 0.1) of your fibromyalgia

patients who've required massive doses before they've responded. Is this true?

But the explanation I see most commonly for " thyroid hormone resistance "

suggests that TSH levels are normal---see, for example, the link

(http://www.thyrolink.com/thyint/3-96int.htm#resist) which explains that, in

cases of resistance, " administration of supraphysiologic doses of thyroid

hormone fail to suppress TSH secretion. "

Dr. Lowe: When supraphysiologic dosages of thyroid hormone fail to suppress TSH

secretion, the patient has " general " resistance to thyroid hormone. This

classification of thyroid hormone resistance is different from the one that

manifests as fibromyalgia in many patients. The latter classification is termed

" peripheral " resistance to thyroid hormone. I will explain the difference

between general and peripheral resistance.

The classification of thyroid hormone resistance is based on whether (1) the

pituitary gland and (2) the other tissues of the body (referred to as

" peripheral " tissues) are involved in the patient's resistance. In general

resistance, both the pituitary gland and the peripheral tissues are partially

resistant to thyroid hormone. The patient's thyroid hormone levels are elevated,

but his TSH level and his peripheral tissue metabolism are usually normal.

Here's why:

In normal functioning of the hypothalamic-pituitary-thyroid axis, when the

amount of thyroid hormone in the blood reaches an appropriate level, it then

inhibits secretion of TSH by the pituitary gland (this is a normal " feedback "

mechanism). But, when the pituitary tissue is resistant to thyroid hormone, much

larger amounts are necessary to suppress TSH secretion. When the peripheral

tissues are also partially resistant, large amounts of thyroid hormone are

needed to " override " the resistance and drive the subnormal metabolism in the

periphery to a higher, normal rate. Typically, when these large amounts of

thyroid hormone (secreted by a thyroid gland stimulated by large amounts of TSH

from a resistant pituitary) finally increase enough to normalize the metabolic

rate of the patient's peripheral tissues, the pituitary tissue also finally

responds to this amount by reducing its secretion of TSH into the normal range.

Thus, patients with general resistance usually have clinically

normal peripheral tissue metabolism with high levels of thyroid hormone in the

blood, and a normalized level of TSH (finally suppressed only by the high blood

levels of thyroid hormone). In this way, the circulating levels of thyroid

hormone are kept high enough to override the peripheral tissue resistance (with

normalized metabolism) and the pituitary resistance (with normalized TSH). In

other words, many general resistance patients appear clinically normal except

for the high thyroid hormone levels.

In peripheral resistance to thyroid hormone, only the peripheral tissues are

resistant. The pituitary tissue responds normally to a normal amount of thyroid

hormone in the blood, and it decreases its TSH output when the blood levels

signal that it should do so. Normal blood levels of thyroid hormone, then,

properly suppress pituitary gland release of TSH, and keep the circulating TSH

levels normal. What's important to realize in this scenario is that the feedback

between the pituitary gland and the thyroid gland is normal, and both glands

secrete normal amounts of their respective hormones. But the normal thyroid

hormone levels are insufficient to override the partial resistance of tissues

other than the pituitary--that is the peripheral tissues. As a result,

metabolism in the peripheral tissues is subnormal. To speed peripheral tissue

metabolism up to normal, the peripheral resistance patient must use large

dosages of thyroid hormone. But the effect of these large dosages on the

normally responsive pituitary tissue is suppression of the TSH. Thus, secretion

of TSH, and its circulating level, are extremely low.

Unfortunately, most physicians become alarmed when they measure the TSH level in

such a patient and find it extremely low. Physicians have been taught that a low

TSH level means only one thing in a patient taking thyroid hormone--the dosage

is too high and is going to harm the patient. It will take some years for

physicians to learn about peripheral resistance to thyroid hormone and to

understand the odd test values these patients have when taking effective dosages

of thyroid hormone. Patients with peripheral resistance must take

TSH-suppressing dosages of thyroid hormone to have normal peripheral tissue

metabolism. But there is nothing whatsoever harmful to these patients in having

their TSH suppressed by these dosages of thyroid hormone. In fact, it would be

harmful for most of them not to take such dosages. The adverse consequences

include conditions such as fibromyalgia, chronic fatigue syndrome, and liver and

cardiovascular diseases.

Here's the link where I got this info:

http://www.drlowe.com/QandA/askdrlowe/resistnc.htm

tina8386@... wrote:Lab Studies:

The sensitive TSH assay is the most useful test in screening for

hypothyroidism and for confirming of the diagnosis. Additional tests

of free T4, total T4, T3 resin uptake, thyroid autoantibodies

(antimicrosomal or antithyroid peroxidase [anti-TPO]), and

antithyroglobulin (anti-Tg) may be helpful to determine the etiology.

Hypothyroidism is virtually the only disease that raises TSH levels

in a sustained fashion. As the TSH level increases, an increase in T4

conversion to T3 occurs; thus, T3 levels are maintained. In early

hypothyroidism, TSH is increased, T4 is normal to low, and T3 is

normal.

Newer and more sensitive generations of TSH assays can detect levels

as low as 0.01 mU/L. (The normal range of TSH value is

0http://www.drlowe.com/QandA/askdrlowe/resistnc.htm.4-4 mU/L.)

In most healthy patients, TSH values are 0.5-1.5 mU/L. TSH levels

peak in the evening and are lowest in the afternoon, with marked

variations due to physiologic conditions such as illness, psychiatric

disorders, and low energy intake. A threshold for TSH inhibition may

exist, as evidenced by the finding that some patients have a normal

TSH level and low free T4 levels.

A free T4 test is recommended over a total T4 test or other

measurement because it is not affected by thyroid hormone binding

proteins.

A free T3 test, as with a T3 test, may be indicative; however,

results are frequently within reference ranges early in the disease.

In some situations, the level of thyroid hormones (eg, free T4) may

be a better indicator of thyroid status.

In severely ill patients with non–thyroid disease, TSH secretion is

decreased, T4 is decreased, and T3 is markedly decreased. In these

patients, the primary abnormality is the peripheral production of

thyroid hormones (mostly T3).

The TRH stimulation test is rarely needed now because of improved TSH

assays. It may be helpful to confirm hypothyroidism by an exaggerated

TSH response in patients who have a low free T4 level with a normal

TSH level.

TSH assays are not useful in patients with pituitary or hypothalamic

failure and secondary hypothyroidism. In these patients, TSH levels

are low in the face of low free T4 and low free T3 levels. Since

isolated pituitary loss of TSH is very rare, other signs and symptoms

to support the diagnosis of pituitary failure and secondary

hypothyroidism are usually present.

[Guest guest]

This is what my cousin - a neurosurgeon - also said I have. I only

feel good if the FT3 and FT4 are in the hyper range. My TSH was 0.01

and I was so hypo I could barely stay awake. She said the thyroid

hormone is in the blood, but not in the cells, and to forget blood

tests.

Jan

>

> I need help in making sense of the information below (from Dr.

Lowe's site). I'm trying to understand this...want to make sure you

all get out of this what I'm getting. Here's my understanding (put

very simplistically)

>

> Peripheral tissues are include any of the tissues (other than the

pituitary) that are resistant to thyroid hormones. So since the

pituitary is getting enough hormone, then someone with this problem

would need more thyroid hormone. This suppresses TSH...it will show

in hyper range...but the peripheral tissues are not getting enough

thyroid hormone...thus peripheral resistance.

>

> Is this how you all understand it?

>

> My neurologist kept trying to explain to me what he felt was

happening and I could never understand it. I think I finally do. He

kept telling me he didn't think my brain cells were getting enough

thyroid hormone, and that even though my TSH showed that I was in the

hyper range, he felt I was undermedicated.

>

> So my brain cells would be peripheral tissues.

>

> The nurse practitioner I saw today was telling me it didn't matter

that my TSH was so low because I don't have symptoms of being over-

medicated; my symptoms are still hypo symptoms. I don't remember a

thing she said except that you can have a low TSH like mine, and it

may LOOK like hyperthyroidism, but it's not. I was foggy and just

don't remember what she said.

>

> Anyway, how uncanny you posted this article tonight...just as I was

reading this.

>

> Questions, Comments, Opinions WANTED....Thanks, Sheila

[Guest guest]

yeah, it definitely sounds like you have this problem! hugs, sheila

janjv1311 <janaina@...> wrote:This is what my cousin - a neurosurgeon

- also said I have. I only

feel good if the FT3 and FT4 are in the hyper range. My TSH was 0.01

and I was so hypo I could barely stay awake. She said the thyroid

hormone is in the blood, but not in the cells, and to forget blood

tests.

Jan

>

> I need help in making sense of the information below (from Dr.

Lowe's site). I'm trying to understand this...want to make sure you

all get out of this what I'm getting. Here's my understanding (put

very simplistically)

>

> Peripheral tissues are include any of the tissues (other than the

pituitary) that are resistant to thyroid hormones. So since the

pituitary is getting enough hormone, then someone with this problem

would need more thyroid hormone. This suppresses TSH...it will show

in hyper range...but the peripheral tissues are not getting enough

thyroid hormone...thus peripheral resistance.

>

> Is this how you all understand it?

>

> My neurologist kept trying to explain to me what he felt was

happening and I could never understand it. I think I finally do. He

kept telling me he didn't think my brain cells were getting enough

thyroid hormone, and that even though my TSH showed that I was in the

hyper range, he felt I was undermedicated.

>

> So my brain cells would be peripheral tissues.

>

> The nurse practitioner I saw today was telling me it didn't matter

that my TSH was so low because I don't have symptoms of being over-

medicated; my symptoms are still hypo symptoms. I don't remember a

thing she said except that you can have a low TSH like mine, and it

may LOOK like hyperthyroidism, but it's not. I was foggy and just

don't remember what she said.

>

> Anyway, how uncanny you posted this article tonight...just as I was

reading this.

>

> Questions, Comments, Opinions WANTED....Thanks, Sheila

[Guest guest]

I am feeling good now that I've decided to skip the blood tests. I am

sure the people from my health insurance are happy too - it was

US$300 in tests every 6 weeks, ouch.

Jan

This is what my cousin - a

neurosurgeon - also said I have. I only

> feel good if the FT3 and FT4 are in the hyper range. My TSH was

0.01

> and I was so hypo I could barely stay awake. She said the thyroid

> hormone is in the blood, but not in the cells, and to forget blood

> tests.

>

>

> Jan

>