| Weight gain and the TSH (at Thyroid Science) |

| Conversion of T4 to reverse T3: Summary |

 

Continued from bottom of left column . . .

March 24, 1999
Question: In reading your Web site and published articles, I see that you have not paid attention to high reverse-T3 as a cause of thyroid hormone resistance in fibromyalgia. Why have you and other fibromyalgia researchers not given attention to high reverse-T3 as a cause of fibromyalgia?

Dr. Lowe: Some readers will not be familiar with reverse-T3, and I know from experience that many others harbor misconceptions about the molecule. Because of this, I have summarized in the box below what we know about reverse-T3. I've answered your question below the summary.

Conversion of T4 to T3 and
Reverse-T3: A Summary

The thyroid gland secretes mostly T4 and very little T3. Most of the T3 that drives cell metabolism is produced by action of the enzyme named 5'-deiodinase, which converts T4 to T3. (We pronounce the "5'-" as "five-prime.") Without this conversion of T4 to T3, cells have too little T3 to maintain normal metabolism; metabolism then slows down. T3, therefore, is the metabolically active thyroid hormone. For the most part, T4 is metabolically inactive. T4 "drives" metabolism only after the deiodinase enzyme converts it to T3.

Another enzyme called 5-deiodinase continually converts some T4 to reverse-T3. Reverse-T3 does not stimulate metabolism. It is produced as a way to help clear some T4 from the body.

Under normal conditions, cells continually convert about 40% of T4 to T3. They convert about 60% of T4 to reverse-T3. Hour-by-hour, conversion of T4 continues with slight shifts in the percentage of T4 converted to T3 and reverse-T3. Under normal conditions, the body eliminates reverse-T3 rapidly. Other enzymes quickly convert reverse-T3 to T2 and T2 to T1, and the body eliminates these molecules within roughly 24-hours. (The process of deiodination in the body is a bit more complicated than I can explain in this short summary.) The point is that the process of deiodination is dynamic and constantly changing, depending on the body's needs.

Under certain conditions, the conversion of T4 to T3 decreases, and more reverse T3 is produced from T4. Three of these conditions are food deprivation (as during fasting or starvation), illness (such as liver disease), and stresses that increase the blood level of the stress hormone called cortisol. We assume that reduced conversion of T4 to T3 under such conditions slows metabolism and aids survival.

Thus, during fasting, disease, or stress, the conversion of T4 to reverse-T3 increases. At these times, conversion of T4 to T3 decreases about 50%, and conversion of T4 to reverse-T3 increases about 50%. Under normal, non-stressful conditions, different enzymes convert some T4 to T3 and some to reverse-T3. The same is true during fasting, illness, or stress; only the percentages change--less T4 is converted to T3 and more is converted to reverse-T3.

The reduced T3 level that occurs during illness, fasting, or stress slows the metabolism of many tissues. Because of the slowed metabolism, the body does not eliminate reverse-T3 as rapidly as usual. The slowed elimination from the body allows the reverse-T3 level in the blood to increase considerably.

In addition, during stressful experiences such as surgery and combat, the amount of the stress hormone cortisol increases. The increase inhibits conversion of T4 to T3; conversion of T4 to reverse-T3 increases. The same inhibition occurs when a patient has Cushing's syndrome, a disease in which the adrenal glands produce too much cortisol. Inhibition also occurs when a patient begins taking cortisol as a medication such as prednisone. However, whether the increased circulating cortisol occurs from stress, Cushing's syndrome, or taking prednisone, the inhibition of T4 to T3 conversion is temporary. It seldom lasts for more than one-to-three weeks, even if the circulating cortisol level continues to be high. Studies have documented that the inhibition is temporary.

A popular belief nowadays (proposed by Dr. Dennis Wilson) has not been proven to be true, and much scientific evidence tips the scales in the "false" direction with regard to this idea. The belief is that the process involving impaired T4 to T3 conversion—with increases in reverse-T3—becomes stuck. The "stuck" conversion is supposed to cause chronic low T3 levels and chronically slowed metabolism. Some have speculated that the elevated reverse-T3 is the culprit, continually blocking the conversion of T4 to T3 as a competitive substrate for the 5’-deiodinase enzyme. However, this belief is contradicted by studies of the dynamics of T4 to T3 conversion and T4 to reverse-T3 conversion. Laboratory studies have shown that when factors such as increased cortisol levels cause a decrease in T4 to T3 conversion and an increase in T4 to reverse-T3 conversion, the shift in the percentages of T3 and reverse-T3 produced is only temporary.

To answer your question: In a 1994 article, I did write of my testing of fibromyalgia patients for laboratory evidence of elevated reverse-T3. [Lowe, J.C., Eichelberger, J., Manso, G., and Peterson, K.: Improvement in euthyroid fibromyalgia patients treated with T3. J. Myofascial Ther.,1(2):16-29, 1994.] During one year, I tested 50 fibromyalgia patients to see if they had laboratory values that would suggest that they had impaired conversion of T4 to T3 with elevated reverse-T3. I've also tested other patients since 1994. However, I have not found laboratory evidence of impaired T4 to T3 conversion in a single patient.

Also, if impaired conversion was the source of the problem in my fibromyalgia patients, they would respond to a normal physiologic dosage of T3. However, most euthyroid fibromyalgia patients require far more than normal physiologic dosages to overcome their thyroid hormone resistance.

Finally I decided that if some patients' fibromyalgia symptoms do indeed result from impaired conversion of T4 to T3, it is a rare phenomenon. I could no longer justify charging patients for the laboratory tests that would identify impaired conversion. As a result, I don't even bother ordering the tests any longer. This is the reason that you haven't read about impaired conversion of T4 to T3 and elevated reverse-T3 at this Web site or in more of our published articles.