RT3/T-3/Cortisol/Synthroid

February 13, 2004

Thought this was interesting.

IN MANY PATIENTS, SYNTHROID ACTUALLY DECREASES THYROID ACTIVITY.

How can taking thyroid hormone impair the cellular response to the

thyroid gland? It seems illogical - so, to explain ...

The thyroid gland produces T4 and T3 in an approximate ratio of

2.5:1. T3 is the active thyroid hormone for which every cell in the

body has receptors. T4, the storage form of thyroid hormone,

circulates and is converted as needed into T3 by the liver, and also

to some extent by the kidney and other tissues. An insignificant

amount of T4 is converted into reverse T3 (RT3), which has no

biological activity, other than that it binds with the T3 receptor

sites, thus blocking the action of T3.

Under normal conditions this small percentage of RT3 with respect to

T3 creates no problems. However, in a stress response that involves

excess cortisol output, the cortisol inhibits the conversion of T4

to T3, while simultaneously favoring the conversion of T4 to RT3.

Stress of sufficient intensity or duration results in a RT3

dominance that persists even after the stress passes and the

cortisol level falls back to normal. This condition is complicated

by the fact that RT3 itself behaves much like cortisol in that it

blocks the conversion of T4 to T3.

Thus is created a condition in which there is insufficient thyroid

activity despite normal thyroid gland output (and a normal serum

thyroid hormone profile).

Consider that very carefully.

The particular thyroid dysfunction you are learning about does not

involve insufficient thyroid gland output of T4 and T3, but rather

an inadequate peripheral conversion of T4 (the storage form of

thyroid hormone) into the active T3. I know of two names by which

this clinical condition has been called: Low T3 syndrome, and

Reverse T3 dominance syndrome.

What does all this have to do with Synthroid?

Synthroid is pure T4, with no active hormone. The idea (hope) in

prescribing it is that the T4 will fill the roll of the underactive

thyroid gland, and be converted to active T3 as needed. For some

patients with a primary thyroid insufficiency the T4 works

beautifully:

- elevated serum TSH and low T4 return to normal - subnormal body

temperature rises to average 98.6 - a sluggish pulse rises to 72 -

elevated serum cholesterol falls toward 200 - fatigue improves

dramatically - the somnolence by day and insomnia at night improves -

fluid retention decreases - % body fat decreases - cramping and

hypertonic muscles are relieved - deep tendon reflex recovery

normalizes - fibromyalgia eases up - apathy or depression gives way

to a new lease on life.

Some of these happy patients may need to rely on Synthroid for a

lifetime; others for less than a year. In either case, these are

simple thyroid insufficiencies that respond to a simple, direct

solution.

Regrettably, however, few cases of thyroid insufficiency are this

simple. The most common complication is that many patients with

primary thyroid insufficiency (inadequate thyroid gland output) also

have Reverse T3 dominance syndrome.

What happens when a case of RT3 dominance is given T4 (Synthroid)?

THE PATIENT IS DEVASTATED BY A DOUBLE DOSE OF THYROID DEPRESSION.

First, the thyroid takes a major hit by virtue of Synthroid's

extremely effective pituitary inhibition. You see, the pituitary

relies on feedback from the thyroid in the form of T4 to determine

its output of TSH to stimulate thyroid production. Under normal

circumstances, this is a very effective feedback loop.

The problem with Synthroid is that it takes so little T4 to make the

pituitary happy. In fact, the pituitary can become quite complacent

in response to T4 feedback long before there is adequate thyroid

function throughout the body. A satisfied pituitary sends no TSH to

the thyroid; and no TSH to the thyroid means depressed T4 and T3

production by the thyroid.

What are you left with now? A patient who had low T3 to begin with,

yet whose T3 insufficiency is being further exacerbated by

inadequate TSH stimulation.

But Synthroid's depression of primary T3 production is only half of

its 1-2 knock out punch. What do you think happens to this

pharmacological dose of T4 in a patient that is already suffering

from a stress-related excess conversion of T4 to T3? You guessed it -

the Synthroid is not converted into T3 but into RT3, which, as you

have already learned, further blocks thyroid function peripherally.

Is it any wonder you have so many patients for whom Synthroid has

supposedly restored normal thyroid function, yet who have all the

hypothyroid symptoms they began with, and more!

The clinical significance of Synthroid damage cannot be overstated;

nor can the surprisingly high incidence of RT3 dominance. Some of

the stressors that have been shown to cause low T3 syndrome or

reverse T3 dominance are fasting (including repeated weight loss

diets), surgery, burn trauma, alcoholism, endotoxin injection, and

the clinical use of glucocorticoids including cortisone shots and

prednisone therapy. The one common finding that all patients

subjected to these stressors show, in addition to low T3 and

elevated RT3 levels, is excess cortisol.

More on how to deal with this red flag in next month's Letter.

Meanwhile - examine the list of references provided below.

In the New Year, may you experience clinical success beyond your

greatest expectations.

Guy R. Schenker, D.C.

Yu, Effect of endotoxin on hormonal responses, Am J Vet Res. Feb,

1998.

Hackney, Effects of high altitude and cold exposure on resting

thyroid hormone concentrations, Aviat Space Environ Med, Apr, 1995.

Arunabh, Changes in thyroid hormones in surgical trauma, J Postgrad

Med, Jul-Sep, 1992.

Langer, Acute development of low T3 syndrome and changes in

pituitary-adrenocortical function after elective cholecystectomy in

women, Scand J Clin Lab Invest, May, 1992.

Juma, Alterations in thyroid hormones, cortisol, and catacholamine

concentration in patients after orthopedic surgery, J Surg Res, Feb,

1991. Herrmann, Low T3 syndrome and chronic inflammatory rheumatism,

Z Gesamte Inn Med, Sep, 1989. (German)

Dolecek, Endocrine changes after burn trauma, Keio J Med, Sep, 1989.

Dennhardt, Patterns of endocrine secretions during sepsis, Prog Clin

Biol Res, 1989.

Keck, Alcohol and endocrinologic homeostasis, Z Gastroenterol, Oct,

1988. (German)

Kjellman, Reverse T3 levels in affective disorders, Psychiatry Res,

Sep, 1983.

Kitahara, Pituitary-thyroid function in patients with Cushing's

Syndrome, Nippon Naibunpi Gakkai Zasshi, Aug, 1983. (Japanese)

Azukizawa, Effect of a single dose of glucocorticoid on the diurnal

variations of TSH, T3, RT3, and cortisol in normal men, Endoc Rinol

Jpn, Dec, 1979.

Schimmel, Thyroidal and peripheral production of thyroid hormones,

ls of Internal Medicine, 1997.

Felicetta, Effects of illness on thyroid function tests, Post

Graduate Medicine, 1989.

Vagenakis, Diversion of peripheral thyroxin metabolism from

activating to inactivating pathways during complete fasting, J Clin

Endocrine Metab, 1975.

Mc, Transient reduction of metabolic rate by food restriction,

Am J Clin Nutr, 1989.

Elliot, Sustained depression of the resting metabolic rate after

massive weight loss, Am J Clin Nutr, 1989.

Nicoloff, Peripheral auto regulation of T4 to T3 conversion in man,

Hormone Metabolism Research Supplement, 1984.

Fzabolcs, The possible reason for RT3 increase in old people, Acta

Medica Academia Scientarium Hunaricae Tomes, 1982.

February 13, 2004

Loved it - great explanation to pass along to whomever will listen.... Could we

please have the link?

Thanks!

Patti in Mi